Randomised controlled trial of mānuka oil-based ECMT-154™ vs vehicle control for the topical treatment of eczema, conducted in community pharmacies in New Zealand

Randomised controlled trial of mānuka oil-based ECMT-154™ vs vehicle control for the topical treatment of eczema, conducted in community pharmacies in New Zealand | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Randomised controlled trial of mānuka oil-based ECMT-154™ vs vehicle control for the topical treatment of eczema, conducted in community pharmacies in New Zealand Gabrielle Shortt, Georgina Bird, Nicholas Shortt, Kyley Kerse, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7124892/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Eczema is a chronic skin condition, characterised by inflammation, erythema, and pruritis. Usage of topical therapies containing botanical extracts is common, however evidence of efficacy is often lacking. This trial investigated the safety and efficacy of a mānuka-oil based cream, 2% ECMT-154, versus vehicle control (VC) for the topical treatment of eczema. Methods This single-blind, parallel group randomised controlled trial was undertaken in 11 community pharmacies across New Zealand. Adults with moderate-to-severe eczema (Patient Oriented Eczema Measure [POEM] ≥ 8 to ≤ 24) were randomized 1:1 to topical 2% ECMT-154 or VC cream, applied twice daily for six weeks. The primary outcome was POEM at week six. Results 118 participants were recruited between 20 th January 2022 and 22 nd May 2023. Between baseline and week six mean POEM score (standard deviation) improved from 16.3 (4.2) to 8.8 (5.7) in the ECMT-154 group, and from 16.9 (3.8) to 8.8 (5.7) in the VC group, a between group difference of -0.38 (95% CI: -2.58 to 1.82, p=0.74). No statistically significant differences were observed across all secondary outcome measures, and no serious adverse events were reported. Conclusions Whilst symptoms of eczema improved in both treatment groups, there was no evidence of a difference in efficacy between ECMT-154 and VC cream in the treatment of eczema. Eczema Emollient Botanical therapy pharmacy-based research network Decentralised Paediatrics atopic dermatitis Figures Figure 1 Figure 2 Background Eczema is a term encompassing a collection of chronic inflammatory skin conditions with similar clinical characteristics (1,2). Eczema is primarily characterised by xerosis and pruritis, and associated scratching may result in skin damage and secondary infections (3). The disease burden in New Zealand is high, with Māori and Pacific populations disproportionally affected (4,5). In addition to physical symptoms, there may be significant social stigma and psychological sequalae (6). Eczema results from a complex interplay of genetic factors, environmental influences and immune system activation (7,8). Pathogenic manifestations of eczema include impaired skin barrier, systemic type 2 immune response and secondary infections (9–11). The immune dysregulation in patients with eczema is associated with CD4+ T cells (Th) and upregulated expression of Th2 and Th22 cytokines, resulting in chronic inflammation (8,12–14). There is no available cure for eczema, with treatment focused on the management of symptoms, maintaining skin integrity, and disease control (15,16). Standard treatment approaches include moisturisers and emollients to maintain skin integrity and topical corticosteroids to treat the inflammation that occurs during symptom flares (15–17). While the efficacy of topical corticosteroids is well established in the management of eczema exacerbations, compliance is low due to patient anxiety around their use (15,16). Side effects can be localised or systemic, including impaired wound healing, skin atrophy, pigmentary change, adrenal insufficiency, osteoporosis and many others (18). Consequently, alternative treatment modalities are attractive, with 62% of patients surveyed responded that they would prefer a nonsteroidal treatment when given multiple treatment options (19). Mānuka ( Leptospermium scoparium ) is a plant native to New Zealand and South-East Australia long used in traditional medicine to treat skin infections, pruritus, fever and cough (20). Modern usage of mānuka centres around the extracted essential oil, the composition of which can be highly variable depending on source and season of harvest. For example Mānuka harvested from the East Coast of New Zealand’s north island is particularly rich in β-triketones which form the basis of the triketone class of herbicides, considered ecologically friendly and safe (21). A recent randomised controlled trial (RCT) undertaken by our group has demonstrate the efficacy of an essential oil extract from the closely related kānuka oil in adult eczema (22). Although similar topical formulations are available containing mānuka oil, no clinical trials have been conducted supporting use in eczema. ECMT-154 (Manuka Bioscience Ltd, Auckland, NZ) is a topical formulation comprised of mānuka oil β-triketones and palmarosa oil, both of which have demonstrated antimicrobial and anti-inflammatory activity in vitro (23–25). Mānuka oil inhibits the release of inflammatory cytokine tumour necrosis factor α (TNF- α) (23,26). Geraniol, a palmarosa oil bioactive, modulates inflammatory pathways by downregulating the expression of TNF-α, interleukin-6, and interleukin-1β (24,27–29). Mānuka and palmarosa oils have also exhibited antimicrobial activity against gram-positive Staphylococcus aureus (25,30–32). These properties may provide therapeutic and prophylactic benefits, to alleviate inflamed lesions during exacerbations, and reducing the risk of secondary infection development. We report a 118-participant randomised controlled trial comparing mānuka-oil triketones based 2% ECMT-154 compared with vehicle control cream, within a nationwide community Pharmacy Research Network. Methods Trial Design This study was a single blind, parallel group, superiority RCT in a community setting. Participants were assigned 1:1 to ECMT-154 in emollient base or vehicle control for the treatment of eczema. The primary outcome variable was the difference in Patient Oriented Eczema Measure (POEM) score at week six. The trial design and methods have been previously reported (33). The study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12622000684729) on 18 th of August 2021. Participants Adults aged between 18 and 65 years, with a doctor’s diagnosis of eczema and a baseline POEM score ≥8 and ≤24 were recruited, representing moderate to severe eczema (34). Exclusion criteria included use of any antibiotics, corticosteroids, or antihistamines within the last two weeks; use of immunomodulatory medications within the last four weeks; currently pregnant or breastfeeding; cutaneous mycotic or bacterial disease; and any skin condition which may have affected the assessment of eczema. Setting and location This study was conducted using the Medical Research Institute of New Zealand (MRINZ) Pharmacy research Network (PRN), an established network of research trained community pharmacies in New Zealand, coordinated centrally by researchers at the MRINZ (35,36). This trial was conducted in 11 community pharmacies nationwide. Interventions Study interventions were 2% ECMT-154 and vehicle control cream, compounded by Optimus Healthcare, Auckland, New Zealand, in accordance with Good Manufacturing Practice standards. Both intervention groups were instructed to apply their treatment twice daily, for six weeks. The study treatment replaced all moisturisers and barrier creams. Usual soap and body wash was replaced by supplied sodium laurel sulphate (SLS) free aqueous cream (Boucher & Muir Pty Ltd, Auckland NZ or Home Essentials, Auckland NZ). Outcomes The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core set of outcome measures for studies in eczema (37). Patient oriented eczema measure (POEM) has been established as the preferred instrument to measure patients symptoms (38), so was selected as primary outcome to assess patient reported symptoms of eczema. Secondary outcomes for the study included the proportion of participants with ≥4 reduction in POEM score (termed responders (39)); difference in Patient Oriented SCORing Atopic Dermatitis (PO-SCORAD) (40) at week six; difference in Dermatology Life Quality Index (DLQI) (41,42) at week six. Participant acceptability was assessed using Treatment Satisfaction Questionnaire for Medication (TSQM) Version II (43) and Numerical Rating Scale (NRS) of the acceptability of the treatment. Treatment safety was assessed by comparing withdrawals due to eczema exacerbations; requirement for treatment escalation between groups; and proportion of cutaneous and systemic events between treatment groups. An exploratory outcome for this study compared the difference in pharmacist-assessed SCORing Atopic Dermatitis (SCORAD) score (part B only) (44). The difference in SCORAD scores was compared between blinded pharmacists, and between blinded pharmacists and remote assessment by a blinded dermatologist. Sample size Based on a minimum clinically important difference (MCID) of 3.4 (45) and pooled standard deviation (SD) of 6.0 (22) for the change in POEM score, each treatment group required 50 participants for 80% power, 5% two-sided alpha. Allowing 15% dropout, 59 participants were required per arm (118 total). Statistical analysis Primary outcome analysis, and analysis of secondary POEM, PO-SCORAD, and DLQI outcomes were conducted by ANCOVA with baseline scores as continuous covariates, and randomised treatment as a categorical variable of interest. Analysis of TSQM effectiveness dimension was by simple t-test. Due to normality assumptions not being well met (checked by residual distributions and plots of residuals versus predicted values) TSQM side effects, convenience, and global satisfaction dimensions and NRS acceptability were analysed by a Mann-Whitney U test with the Hodges-Lehmann estimator for location difference and appropriate confidence intervals. Analysis of proportions were by estimation of relative risk and associated confidence intervals. Agreement between pharmacist and dermatologist SCORAD was by linear mixed model, with participant treated as a random effect, and an odds ratio estimating the probability of a higher versus lower rating. Analysis was separated by intention to treat (ITT) and per protocol set (PPS), with ITT as primary analysis. ITT population included all participants randomized. PPS included all participants with at least 80% completed data, including primary outcome, with no significant protocol deviations influencing POEM. For inclusion is PPS, participants were required to adhere to treatment instruction, measured by >80% daily adherence. Missing outcome data were not imputed. SAS software version 9.4 was used for analysis. Randomisation and masking Study participants were electronically randomized 1:1 using a block size four, according to a randomisation schedule generated by a blinded biostatistician. Randomisation took place at the pharmacy, and study investigators had no access to the randomisation schedule. Interventional treatments were labelled by an external compounding pharmacist as “Treatment G” and “Treatment H” in non-descript packaging for the purpose of blinding. Study investigators at the pharmacies and MRINZ were blinded. Participants were not told if they received the active or control cream, however the distinctive smell of ECMT-154 was unable to be matched. Therefore, this study will conservatively be classified as single blind rather than double blind, due to high risk for participant unblinding. Data Capture All study related data, including informed consent, was captured using direct electronic data capture via REDCap electronic data capture tools hosted at MRINZ (46,47). At pharmacy sites, study data was entered using supplied tablet devices. Online study diaries and questionnaires were completed by study participants on their personal devise, accessed through unique links assigned for each time point. Direct electronic data capture enabled real-time data validation through entry range limits, required fields, and logic checks. Study data was securely stored on password-protected servers, accessible only to trial staff and study monitors. Investigators will retain access to the final trial dataset. Monitoring An independent study monitoring plan was in place to ensure compliance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Good Clinical Practice, and New Zealand ethical guidelines. Any substantial protocol deviations or violations were reported to the New Zealand ethics committee in accordance with approval requirements. Results Participants were recruited from 20 January 2022 to 22 May 2023 across 11 pharmacies in New Zealand. The final participant follow-up was complete by 19 July 2023. Out of 153 individuals assessed for eligibility, 118 were randomized to 2% ECMT-154 (n=59) or vehicle control (n=59)(Figure 1). The participants are described in Table 1. Both groups were well matched in characteristics according to age, sex, and baseline measurements. The study population was primarily female (72%), with a mean (SD) age of 30.35 (11.3). All, n=118 ECMT-154, n=59 Vehicle control, n=59 Continuous variables Mean (SD) [range] Age (years) 30.4 (11.3) [18-64] 27.9 (9.8) [18-63] 32.8 (12.3) [18-64] POEM at baseline 16.6 (4.0) 16.3 (4.2) 16.9 (3.8) Categorical variables N/118 (%) N/59 (%) N/59 (%) Female sex 85 (72.0) 40 (67.8) 45 (76.3) Ethnicity Asian 12 (16.1) 12 (20.3) 7 (11.9) European 67 (56.8) 32 (54.2) 35 (59.3) Māori 26 (22.0) 10 (16.9) 16 (27.1) MELAA 1 (0.8) 1 (1.7) 0 (0.0) Pacific 4 (3.4) 4 (6.8) 0 (0.0) Table 1. Participant characteristics There was no evidence of a difference in POEM score at week six between ECMT-154 and vehicle control (p=0.74) (Table 2). Both groups showed mean improvement in POEM score between baseline and week six greater than the pre-defined MCID of 3.4 (8.2 points for EMT-154 and 8.1 points for vehicle control) (Figure 2). Positive ‘responder’ participants were defined as having an improvement in POEM score of four or more points over the six weeks of study. Both groups had a high proportion of responders to treatment (ECMT-154 = 77.2%, vehicle = 77.4%), however there was no difference between groups (p=0.98). ECMT-154 Vehicle control Mean difference (95% CI) p-value Baseline (n=59) Week 6 ITT (n=57) Week 6 PPS (n=24) Baseline (n=59) Week 6 ITT (n=53) Week 6 PPS (n=30) Intention to treat analysis Per protocol analysis POEM 16.3 (4.2) 8.1 (6.2) 6.75 (5.29) 16.9 (3.8) 8.8 (5.7) 8.40 (6.15) -0.38 (-2.58 to 1.82) p=0.74 -0.49 (-3.70 to 2.72) p=0.76 Table 2. Data reported as mean (SD) unless otherwise specified. ITT= Intention to treat analysis group. PP = Per protocol analysis group There was no significant difference in PO-SCORAD between treatment groups at week six (Table 3). The mean (SD) was 23.9 (15.6) for ECMT-154 group and 23.2 (13.7) for the vehicle control group. The mean difference between treatment groups was 0.31 (95% CI -5.05 to 5.67), p=0.91. The mean (SD) change in DLQI scores at week six from baseline was -4.28 for ECMT-154 group and -3.68 for the vehicle control group (Table 3). The mean difference between treatment groups was -0.14 (95% CI -1.74 to 1.47). Although this difference was not significant between groups (p=0.87), the change in DLQI score was larger than the suggested MCID of 4.0 for the ECMT-154 group (48). There was no difference in TSQM-II scores between groups (p=0.66) (Table 3). Both treatment groups had high satisfaction scores in all domains, with particularly high scores in convenience and side effects domains. For overall acceptability NRS, both groups rated study treatment as largely acceptable (Table 3). Median (IQR) for ECMT-154 group was 7 (4 to 9) and 7 (5 to 10) for vehicle control group, p=0.27. ECMT-154 Vehicle Control Relative risk (95% CI) p-value Baseline (n=59) Week 6 (n=57) Baseline (n=59) Week 6 (n=53) POEM number of responders (N[%]) - 44 (77.2) - 41 (77.4) 1.00 (0.81 to 1.22) P=0.98 Mean difference (95% CI) p-value SCORAD Part B Dermatologist 4.9 (2.4) 3.5 (1.9) 4.6 (2.1) 3.8 (2.1) -0.50 (-1.30 to 0.31) p=0.22 PO-SCORAD 39.2 (13.3) 23.9 (15.6) 37.1 (11.8) 23.2 (13.7) 0.31 (-5.05 to 5.67) p=0.91 DLQI 8.9 (5.6) 4.7 (4.8) 8.3 (4.5) 4.4 (4.6) -0.14 (-1.74 to 1.47) p=0.87 TSQM Effectiveness - 55 (22.5) - 57.7 (27.7) -2.73 (-12.24 to 6.78) p=0.57 Hodges Lehmann estimator (95% CI) p-value Acceptability NRS (Median [IQR]) - 7 (4 to 9) - 7 (5 to 10) -1.00 (-2.00 to 0.00) p=0.27 TSQM (Median [IQR]) Side effects - 100 (100 to 100) - 100 (100 to 100) 0.00 (0.00 to 0.00) p=0.79 Convenience - 72.2 (61.1 to 83.3) - 72.2 (66.7 to 83.3) -5.50 (-11.10 to 0.00) p=0.21 Global - 58.3 (50 to 75) - 66.7 (33.3 to 83.3) 0.00 (-16.60 to 8.30) p=0.66 Table 3. Efficacy and acceptability outcomes. Reported in mean (SD) unless otherwise specified. POEM = Patient Orientated Outcome Measure. PO-SCORAD = Patient Orientated Scoring Atopic Dermatitis. DLQI = Dermatology Life Quality Index. NRS = Numerical Rating Scale. TSQM vII= Treatment Satisfaction Questionnaire for Medication version II. Ten total participants discontinued the study intervention due to worsening eczema, treatment side effects, or related adverse events (Table 4). There was no significant difference in the number of withdrawals for worsening eczema between groups; four (6.8%) participants in the ECMT-154 group, and one (1.7%) participant in the vehicle control group (relative risk 3.00, 95% CI 0.32 to 28.02, p=0.31.) There were 18 instances of escalated eczema treatment in the ECMT-154 group (30.5%), and 12 (20.3%) in the vehicle control group (p=0.20). In the ECMT-154 there were 23 related adverse events, compared to 21 in vehicle control group (relative rate 1.10, 95% CI 0.61 to 1.98, p=0.76). Throughout the study only three cases of infective eczema were reported, with two in the ECMT-154 treatment group and one in the vehicle control group. This study provides no evidence to suggest that one treatment group may provide protective effect against infection over the other. ECMT-154 (n=59) Vehicle Control (n=59) Relative Risk (95% CI) Proportion of withdrawal for worsening eczema N(%) 3 (5.1) 1 (1.7) 3.00 (0.32 to 28.02) P=0.31 Proportion of treatment escalation* N(%) 18 (30.5) 12 (20.3) 1.50 (0.79 to 2.83) p=0.20 At least one adverse event N(%) 45 (76.3) 36 (61.1) 1.25 (0.97 to 1.60) p=0.07 At least one related adverse event N(%) 22 (37.3) 18 (30.5) 1.22 (0.74 to 2.03) p=0.44 Relative Rate (95% CI) Total count of adverse events (N) 69 56 1.23 (0.87 to 1.75) p=0.25 Total count of related adverse events (N) 23 21 1.10 (0.61 to 1.98 p=0.76 Table 4. Safety outcomes. Reported as total count unless otherwise specified. * Experienced an adverse event of worsening eczema that required the use of corticosteroids or antibiotics during the treatment period An exploratory analysis compared the in-person pharmacist and remote dermatologist scoring of eczema severity using SCORAD Part B. Pharmacists were significantly more likely to assign higher scores for oozing, excoriation, lichenification, and ichthyosis at baseline than the dermatologist (p<0.001), and more likely to assign lower baseline scores for swelling (p<0.001) (Table 5). At week six, pharmacists were more likely to assign higher scores for oozing (p=0.002), excoriation, and ichthyosis (p<0.001), and lower scores for erythema and swelling (p<0.001). Acceptability of lesion photographs for scoring judged by the study dermatologist, had a median score of 7 on a 10-point scale. Pharmacist versus Dermatologist Odds ratio of higher score (95% CI) Variable Baseline P Value Baseline P value Erythema (Redness) 0.90 (0.53 to 1.52) 0.69 0.24 (0.11 to 0.48) <0.001 Papulation/Oedema (Swelling) 0.16 (0.09 to 0.29) <0.001 0.10 (0.04 to 0.24) <0.001 Oozing/crusting 6.49 (3.21 to 13.10) <0.001 4.92 (1.79 to 13.48) 0.002 Excoriation (Scratch marks) 16.92 (7.49 to 36.21) <0.001 9.85 (3.84 to 25.23) <0.001 Lichenification (Leathery) 2.93 (1.73 to 4.98) <0.001 1.55 (0.85 to 2.83) 0.15 Ichthyosis (Dryness) 51.57 (17.71 to 150.15) <0.001 38.43 <0.001 Table 5. SCORAD (Part B) Inter-rater variability. Pharmacist scoring was conducted in-person. Dermatologist scoring was conducted remotely on a photo of the representative lesion. Discussion This randomised controlled trial has shown no difference in efficacy between 2% ECMT-154 and vehicle control cream for the treatment of moderate to severe eczema. Although there was no difference in any outcome measures between groups, both treatment groups reported an improvement in eczema symtpoms, quality of life with positive treatment acceptability ratings. This suggests the vehicle cream to be an effective emollient and demonstrates the benefit of regular emollient use over six weeks (49). There was no statistically significant difference in the rates of adverse events, withdrawals, escalated eczema treatment and study withdrawals for worsening eczema between groups, although a trend in favour of vehicle control was suggested. Outcome measures were selected for this study as recommended by the HOME, which sets recommended outcome measures for clinical trials in eczema (34,37). Some outcomes, such as Eczema Area and Severity Index (EASI)(50) were not able to be implemented for this study due to requirement for full body assessment and limitations to conduct this within a community pharmacy setting. This study had reasonably high external validity as the decentralised study design allowed for recruitment of a generalisable population from diverse ethnic and socioeconomic backgrounds, and various geographical locations throughout New Zealand. Worldwide, there are well documented barriers which impact participation of indigenous populations in clinical trials, contributing to underrepresentation in clinical research (51,52). In this study, 22% of participants self-identified as Māori, higher than the 2023 census estimate of 19.6% (53), indicating success of leveraging community-based study sites, and provision of multi-lingual information and consent forms. Due to supply issues in New Zealand, the aqueous cream supplier was changed during the study. Both aqueous creams used were SLS-free. To limit confounding effects, the same number of participants in each treatment group received aqueous cream from Boucher & Muiror (ECMT-154: 24 participants, 40.7%; vehicle control: 24 participants, 40.7%) and Home Essentials (ECMT-154: 35 participants, 59.3%; Vehicle control: 35 participants, 59.3%). This study was conducted as a double-blind study, and participants were not informed of treatment allocation. However, the distinctive scent of mānuka and palmarosa oil was unable to be matched in the vehicle control. As a result, participants may have been able to infer their treatment allocation, introducing a potential source of bias. For this reason, the study is conservatively reported as single-blind. The treatment period was limited to six weeks, which is shorter than usual eczema clinical trials. Study duration was selected due to the moderate-to-severe POEM score required by participants, and to minimise the likelihood of participants requiring rescue topical corticosteroids, due to the large impact of these on outcome measures. Assessment over a longer time frame may be beneficial for future research, to evaluate any longer-term remission with use of ECMT-154. This study also explored the feasibility of pharmacist-led eczema severity scoring with remote dermatologist verification via clinical photographs. There was significant disagreement across most domains (Table 5) and quality of photograph was reported as acceptable in only 72.4%, with 16.3% identified as out of focus, 3.4% with poor lighting, 11.3% too far away from the subject, 1.5% of low image resolution, and 1% poor colour balance. Consistency and quality of clinical photographs is required for remote dermatologist SCORAD scoring, potentially contributing to disagreement in assessment between pharmacists and dermatologist. Furthermore, lack of dermatological expertise appeared to result in higher scoring form most pharmacies assessed domains in SCORAD, similar to finding in our groups previous community-based study of eczema (22). Whilst this teledermatology model has significant potential to facilitate pragmatic trials in the community setting, improved pharmacist training and standardised photography protocols are required for future studies to ensure reliable remote assessment. Previous research has supported the use of a topical emollient containing 3% kānuka oil for eczema. (22) Mānuka and kānuka are both members of the Myrtaceae family (54) and have demonstrated similar anti-inflammatory mechanisms in vitro by reducing the production of inflammatory cytokine TNF-α (23). However, this study identified 2% ECMT-154 does not have similar efficacy in vivo. The composition and percentage of ECMT-154 used for the study treatment was based on minimum inhibitory concentrations from in vitro experiments. A 2% concentration of ECMT-154 may have been insufficient to achieve an anti-inflammatory effect in vivo, and higher dose may be necessary for potential clinical benefit. However, there was no data trend towards a significant difference, providing no evidence from this study to support this. Only three cases of infective eczema were reported in this study, two in ECMT-154 treatment group and one in vehicle control group. Therefore, whilst both interventions appear to not increase susceptibility toward infection, no analysis was possible to assess antibacterial actions specifically. ECMT-154 is a purified extract comprising primarily the triketone constituents of mānuka oil, excluding other potentially bioactive metabolites. Mānuka oil comprises numerous active compounds, including sesquiterpenes and flavonoids (21,31,55). These other metabolites may contribute the anti-inflammatory effects of mānuka oil (23). The exclusion of non-triketone components in ECMT-154 may disrupt potential synergistic effects necessary for in vivo efficacy. Future research on optimal concentration of ECMT-154, longer treatment duration or the inclusion of additional bioactive compounds from mānuka could confer any clinical benefit. Conclusions In conclusion ECMT-154 provided no clinical benefit over vehicle control for the topical treatment of eczema. Abbreviations AE Adverse Event DLQI Dermatology Life Quality Index DSMC Data and Safety Monitoring Committee HDEC Health and Disability Ethics Committee ITT Intention-to-treat MCID Minimal Clinically Important Difference NRS Numerical Rating Scale PO-SCORAD Patient-Oriented SCORing Atopic Dermatitis POEM Patient-Oriented Eczema Measure PPS Per Protocol Set RCT Randomised Controlled Trial SAE Serious Adverse Event SCORAD SCORing Atopic Dermatitis SCOTT Standing Committee on Therapeutic Trials Declarations Ethics approval and consent to participate This study was approved by Central Health and Disability Ethics Committee (HDEC reference: 2021 EXP 11490). National Standing Committee on Therapeutic Trials (SCOTT ) approval was obtained (21/SCOTT/118), as required for all clinical trials investigating a new medicine under New Zealand legislation.(56) Electronic written informed consent to participate was obtained from all participants. Conduct of the study was in accordance with guidelines and regulations set forth by HDEC and SCOTT. Patient and public involvement Narrative feedback obtained from participants who took part in a previous community pharmacy-based study at MRINZ(22,35) informed development of the study protocol and data collection tools. Consent for publication Not applicable Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests SH is the inventor of ECMT-154 (as described in International Publication Number WO2022/234340 A1) and a shareholder of Manuka Bioscience. SH was also a contractor (R&D Strategist) at Manuka Bioscience. SH had input into protocol development but was not involved in study conduct or data analysis. AS and GS declare funding from Manuka Bioscience to the MRINZ for the submitted work. There are no other conflicts of interest to declare. Funding This trial is sponsored and funded by Manuka Biosciences Ltd, who received a Callaghan Innovation Project Grant (MBIOS2003) and R&D Loan (MBIOS2001). Author Contributions The study was designed by GS, AS, NS, KK, and AE. With later input from MR, and LR. GS and AS are co-chief investigators with overall responsibility for the trial. GS, GB, RB, AM, and AL managed the study participants and data. MR performed remote dermatologist assessment. AE provided statistical analysis. NS built the REDCap trial database. This manuscript was drafted by GS, all authors were involved in manuscript revision and final approval. Acknowledgements We thank all members of the Pharmacy Research Network; Alexander Pharmacy: Angela Liu; Anderson’s Exchange Pharmacy: Bob Kim; Castle Chemists: Shahlaa Al Salih; Tamatea Pharmacy: Delwyn Simes and Jenny Motley; Ranolf Pharmacy: Carina Soeteman, Kate Milne, and Manawa Cox; Life Pharmacy Te Puke: Hannah Search and Sally Kim; Life Pharmacy Papakura: Chau Ly and Louise Kim; Life Pharmacy New Plymouth: Nai Yeat; Clive’s Chemist: Clive Cannons and Mark Albert Ethics and dissemination: Ethics approval was obtained from Central Health and Disability Ethics Committee on 3 rd December 2021 (reference: 2021 EXP 11490. The Standing Committee on Therapeutic Trails (SCOTT) granted study approval on 20 th September 2021 (reference: 21/SCOTT/118) Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622000684729, the study was registered on 18 th of August 2021. 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Bos JD, Wierenga EA, Sillevis Smitt JH, van der Heijden FL, Kapsenberg ML. Immune dysregulation in atopic eczema. Arch Dermatol. 1992 Nov;128(11):1509–12. Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012 Dec;130(6):1344–54. Dubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Review of Clinical Immunology. 2021 Aug 3;17(8):835–52. Simpson EL. Atopic dermatitis: a review of topical treatment options. Current Medical Research and Opinion. 2010;26(3):633–40. Chong M, Fonacier L. Treatment of Eczema: Corticosteroids and Beyond. Clinical Reviews in Allergy and Immunology. 2016;51(3):249–62. Lee JH, Son SW, Cho SH. A Comprehensive Review of the Treatment of Atopic Eczema. 2016;8(3):181–90. DiRuggiero D, DiRuggiero M. Beyond Skin Deep: The Systemic Impact of Topical Corticosteroids in Dermatology. J Clin Aesthet Dermatol. 2025;18(1-2 Suppl 1):S16–20. Aubert-Wastiaux H, Moret L, Le Rhun A, Fontenoy AM, Nguyen JM, Leux C, et al. Topical corticosteroid phobia in atopic dermatitis: A study of its nature, origins and frequency. British Journal of Dermatology. 2011;165(4):808–14. Mathew C, Tesfaye W, Rasmussen P, Peterson GM, Bartholomaeus A, Sharma M, et al. Mānuka Oil—A Review of Antimicrobial and Other Medicinal Properties. Pharmaceuticals. 2020 Nov;13(11):343. Douglas MH, van Klink JW, Smallfield BM, Perry NB, Anderson RE, Johnstone P, et al. Essential oils from New Zealand manuka: triketone and other chemotypes of Leptospermum scoparium. Phytochemistry. 2004 May;65(9):1255–64. Shortt N, Martin A, Kerse K, Shortt G, Vakalalabure I, Barker L, et al. Efficacy of a 3% Kānuka oil cream for the treatment of moderate-to-severe eczema: A single blind randomised vehicle-controlled trial. eClinicalMedicine. 2022 Sep 1;51:101561. Chen CC, Yan SH, Yen MY, Wu PF, Liao WT, Huang TS, et al. Investigations of kanuka and manuka essential oils for in vitro treatment of disease and cellular inflammation caused by infectious microorganisms. Journal of Microbiology, Immunology and Infection. 2016 Feb 1;49(1):104–11. Wang J, Su B, Zhu H, Chen C, Zhao G. Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK. Exp Ther Med. 2016 Dec;12(6):3607–13. Prashar A, Hili P, Veness RG, Evans CS. Antimicrobial action of palmarosa oil (Cymbopogon martinii) on Saccharomyces cerevisiae. Phytochemistry. 2003 Jul;63(5):569–75. Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, et al. TNF-α and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol. 2014 Jul;134(7):1941–50. Huang Y, Yang XL, Ni YH, Xu ZM. Geraniol suppresses proinflammatory mediators in phorbol 12-myristate 13-acetate with A23187-induced HMC-1 cells. Drug Des Devel Ther. 2018;12:2897–903. Mączka W, Wińska K, Grabarczyk M. One Hundred Faces of Geraniol. Molecules. 2020 Jan;25(14):3303. Ye CJ, Li SA, Zhang Y, Lee WH. Geraniol targets KV1.3 ion channel and exhibits anti-inflammatory activity in vitro and in vivo . Fitoterapia. 2019 Nov 1;139:104394. Bard M, Albrecht MR, Gupta N, Guynn CJ, Stillwell W. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids. 1988 Jun 1;23(6):534–8. Christoph F, Kaulfers PM, Stahl-Biskup E. A comparative study of the in vitro antimicrobial activity of tea tree oils s.l. with special reference to the activity of beta-triketones. Planta Med. 2000 Aug;66(6):556–60. van Klink JW, Larsen L, Perry NB, Weavers RT, Cook GM, Bremer PJ, et al. Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action. Bioorg Med Chem. 2005 Dec 15;13(24):6651–62. Shortt G, Shortt N, Bird G, Kerse K, Lieffering N, Martin A, et al. Mānuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand. BMC Complement Med Ther. 2024 Jan 29;24(1):61. Spuls P i., Gerbens L a. a., Simpson E, Apfelbacher C j., Chalmers J r., Thomas K s., et al. Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement. British Journal of Dermatology. 2017;176(4):979–84. Semprini A, Singer J, Braithwaite I, Shortt N, Thayabaran D, McConnell M, et al. Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial. BMJ Open. 2019 14;9(5):e026201. Semprini A, Singer J, Shortt N, Braithwaite I, Beasley R. Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting. BMJ Open. 2017 Aug 1;7(8):e017766. Schmitt J, Spuls PI, Thomas KS, Simpson E, Furue M, Deckert S, et al. The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials. J Allergy Clin Immunol. 2014 Oct;134(4):800–7. Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients’ perspective. Arch Dermatol. 2004 Dec;140(12):1513–9. Howells L, Ratib S, Chalmers JR, Bradshaw L, Thomas KS, CLOTHES trial team. How should minimally important change scores for the Patient-Oriented Eczema Measure be interpreted? A validation using varied methods. Br J Dermatol. 2018 May;178(5):1135–42. Stalder JF, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, et al. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy. 2011 Aug;66(8):1114–21. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210–6. Ali FM, Johns N, Finlay AY, Salek MS, Piguet V. Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index: evidence of equivalence. Br J Dermatol. 2017 Nov;177(5):1306–15. Atkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health. 2005 Dec;8 Suppl 1:S9–24. Kunz B, Oranje AP, Labrèze L, Stalder JF, Ring J, Taïeb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1997;195(1):10–9. Schram ME, Spuls PI, Leeflang MMG, Lindeboom R, Bos JD, Schmitt J. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy. 2012 Jan;67(1):99–106. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics. 2009;42(2):377–81. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. Basra MKA, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230(1):27–33. van Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BW. Emollients and moisturisers for eczema. Cochrane Database Syst Rev. 2017 Feb 6;2:CD012119. Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol. 2015;172(5):1353–7. Glover M, Kira A, Johnston V, Walker N, Thomas D, Chang AB, et al. A systematic review of barriers and facilitators to participation in randomized controlled trials by Indigenous people from New Zealand, Australia, Canada and the United States. Glob Health Promot. 2015 Mar;22(1):21–31. Schmotzer GL. Barriers and facilitators to participation of minorities in clinical trials. Ethn Dis. 2012;22(2):226–30. Stats NZ. 2023 Census population counts (by ethnic group, age, and Māori descent) and dwelling counts [Internet]. 2024 May [cited 2025 Apr 4]. Available from: https://www.stats.govt.nz/information-releases/2023-census-population-counts-by-ethnic-group-age-and-maori-descent-and-dwelling-counts/ Essien SO, Baroutian S, Dell K, Young B. Value-added potential of New Zealand mānuka and kānuka products: A review. Industrial Crops and Products. 2019 Apr 1;130:198–207. Porter NG, Wilkins AL. Chemical, physical and antimicrobial properties of essential oils of Leptospermum scoparium and Kunzea ericoides . Phytochemistry. 1999 Feb 10;50(3):407–15. Medicines Act 1981 [Internet]. New Zealand Legislation; 2021 Dec [cited 2022 Jun 20]. Report No.: 118. Available from: https://www.legislation.govt.nz/act/public/1981/0118/latest/whole.html#DLM55429 Additional Declarations Competing interest reported. SH is the inventor of ECMT-154 (as described in International Publication Number WO2022/234340 A1) and a shareholder of Manuka Bioscience. SH was also a contractor (R&D Strategist) at Manuka Bioscience. SH had input into protocol development but was not involved in study conduct or data analysis. AS and GS declare funding from Manuka Bioscience to the MRINZ for the submitted work. There are no other conflicts of interest to declare. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7124892","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":510550641,"identity":"3c649ea3-363b-4fd9-b7ea-067a7f8d28d8","order_by":0,"name":"Gabrielle 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00:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7124892/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7124892/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90981461,"identity":"156a082c-1dff-463e-b1eb-930c5e71ac88","added_by":"auto","created_at":"2025-09-10 09:24:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":235327,"visible":true,"origin":"","legend":"\u003cp\u003eStudy CONSORT diagram\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7124892/v1/1fd5d98b2856a5130754109b.png"},{"id":90981501,"identity":"73156f85-74f1-4656-ab1d-a015db60e39e","added_by":"auto","created_at":"2025-09-10 09:24:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":28541,"visible":true,"origin":"","legend":"\u003cp\u003eWeekly mean POEM scores for treatment groups. ECMT-154 group represented by solid line; vehicle control group represented by dashed line. Error bars represent standard error\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7124892/v1/9bc08c0d5741bac06709e55d.png"},{"id":90982909,"identity":"91a5285c-6482-4e0f-a1a0-982a6fadd5f1","added_by":"auto","created_at":"2025-09-10 09:32:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1085152,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7124892/v1/a73874cd-b9ff-4928-a47e-46be7b739c7c.pdf"}],"financialInterests":"Competing interest reported. SH is the inventor of ECMT-154 (as described in International Publication Number WO2022/234340 A1) and a shareholder of Manuka Bioscience. SH was also a contractor (R\u0026D Strategist) at Manuka Bioscience. SH had input into protocol development but was not involved in study conduct or data analysis. AS and GS declare funding from Manuka Bioscience to the MRINZ for the submitted work. There are no other conflicts of interest to declare.","formattedTitle":"Randomised controlled trial of mānuka oil-based ECMT-154™ vs vehicle control for the topical treatment of eczema, conducted in community pharmacies in New Zealand","fulltext":[{"header":"Background","content":"\u003cp\u003eEczema is a term encompassing a collection of chronic inflammatory skin conditions with similar clinical characteristics\u0026nbsp;(1,2).\u0026nbsp;Eczema is primarily characterised by xerosis and pruritis, and associated scratching may result in skin damage and secondary infections\u0026nbsp;(3).\u0026nbsp;The disease burden in New Zealand is high, with Māori and Pacific populations disproportionally affected\u0026nbsp;(4,5).\u0026nbsp;In addition to physical symptoms, there may be significant social stigma and psychological sequalae\u0026nbsp;(6).\u003c/p\u003e\n\u003cp\u003eEczema results from a complex interplay of genetic factors, environmental influences and immune system activation\u0026nbsp;(7,8).\u0026nbsp;Pathogenic manifestations of eczema include impaired skin barrier, systemic type 2 immune response and secondary infections\u0026nbsp;(9\u0026ndash;11).\u0026nbsp;The immune dysregulation in patients with eczema is associated with CD4+ T cells (Th) and upregulated expression of Th2 and Th22 cytokines, resulting in chronic inflammation\u0026nbsp;(8,12\u0026ndash;14).\u003c/p\u003e\n\u003cp\u003eThere is no available cure for eczema, with treatment focused on the management of symptoms, maintaining skin integrity, and disease\u0026nbsp;control (15,16). Standard treatment approaches include moisturisers and emollients to maintain skin integrity and topical corticosteroids to treat the inflammation that occurs during symptom flares (15\u0026ndash;17). While the efficacy of topical corticosteroids is well established in the management of eczema exacerbations, compliance is low due to patient anxiety around their use (15,16). Side effects can be localised or systemic, including impaired wound healing, skin atrophy, pigmentary change, adrenal insufficiency, osteoporosis and many others (18). Consequently, alternative treatment modalities are attractive, with 62% of patients surveyed responded that they would prefer a nonsteroidal treatment when given multiple treatment options (19).\u003c/p\u003e\n\u003cp\u003eMānuka (\u003cem\u003eLeptospermium scoparium\u003c/em\u003e) is a plant native to New Zealand and South-East Australia long used in traditional medicine to treat skin infections, pruritus, fever and cough\u0026nbsp;(20). Modern usage of mānuka centres around the extracted essential oil, the composition of which can be highly variable depending on source and season of harvest. For example Mānuka harvested from the East Coast of New Zealand\u0026rsquo;s north island is particularly rich in\u0026nbsp;\u0026beta;-triketones which form the basis of the triketone class of herbicides, considered ecologically friendly and safe (21).\u0026nbsp;\u0026nbsp;A recent randomised controlled trial (RCT) undertaken by our group has demonstrate the efficacy of an essential oil extract from the closely related kānuka oil in adult eczema\u0026nbsp;(22). Although similar topical formulations are available containing mānuka oil, no clinical trials have been conducted supporting use in eczema. ECMT-154 (Manuka Bioscience Ltd, Auckland, NZ) is a topical formulation comprised of\u0026nbsp;mānuka oil \u0026beta;-triketones and palmarosa oil, both of which have demonstrated antimicrobial and anti-inflammatory activity in vitro\u0026nbsp;(23\u0026ndash;25). Mānuka oil inhibits the release of inflammatory cytokine tumour necrosis factor \u0026alpha; (TNF- \u0026alpha;)\u0026nbsp;(23,26). Geraniol, a palmarosa oil bioactive, modulates inflammatory pathways by downregulating the expression of TNF-\u0026alpha;, interleukin-6, and interleukin-1\u0026beta;\u0026nbsp;(24,27\u0026ndash;29). Mānuka and palmarosa oils have also exhibited antimicrobial activity against gram-positive \u003cem\u003eStaphylococcus aureus\u0026nbsp;\u003c/em\u003e(25,30\u0026ndash;32). These properties may provide therapeutic and prophylactic benefits, to alleviate inflamed lesions during exacerbations, and reducing the risk of secondary infection development.\u003c/p\u003e\n\u003cp\u003eWe report a 118-participant randomised controlled trial comparing mānuka-oil triketones based 2% ECMT-154 compared with vehicle control cream, within a nationwide community Pharmacy Research Network. \u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eTrial Design\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was a single blind, parallel group, superiority RCT in a community setting. Participants were assigned 1:1 to ECMT-154 in emollient base or vehicle control for the treatment of eczema. The primary outcome variable was the difference in Patient Oriented Eczema Measure (POEM) score at week six. The trial design and methods have been previously reported\u0026nbsp;(33). The study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12622000684729) on 18\u003csup\u003eth\u003c/sup\u003e of August 2021.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eParticipants\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAdults aged between 18 and 65 years, with a doctor\u0026rsquo;s diagnosis of eczema and a baseline POEM score\u0026nbsp;\u0026ge;8 and\u0026nbsp;\u0026le;24 were recruited, representing moderate to severe eczema\u0026nbsp;(34). Exclusion criteria included use of any antibiotics, corticosteroids, or antihistamines within the last two weeks; use of immunomodulatory medications within the last four weeks; currently pregnant or breastfeeding; cutaneous mycotic or bacterial disease; and any skin condition which may have affected the assessment of eczema.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSetting and location\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted using the Medical Research Institute of New Zealand (MRINZ) Pharmacy research Network (PRN), an established network of research trained community pharmacies in New Zealand, coordinated centrally by researchers at the MRINZ\u0026nbsp;(35,36). This trial was conducted in 11 community pharmacies nationwide. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInterventions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStudy interventions were 2% ECMT-154 and vehicle control cream, compounded by Optimus Healthcare, Auckland, New Zealand, in accordance with Good Manufacturing Practice standards. Both intervention groups were instructed to apply their treatment twice daily, for six weeks. The study treatment replaced all moisturisers and barrier creams. Usual soap and body wash was replaced by supplied sodium laurel sulphate (SLS) free aqueous cream (Boucher \u0026amp; Muir Pty Ltd, Auckland NZ or Home Essentials, Auckland NZ).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Harmonising Outcome Measures for Eczema (HOME) initiative has established a core set of outcome measures for studies in eczema (37). Patient oriented eczema measure (POEM) has been established as the preferred instrument to measure patients symptoms (38), so was selected as primary outcome to assess patient reported symptoms of eczema. Secondary outcomes for the study included the proportion of participants with \u0026ge;4 reduction in POEM score (termed responders (39)); difference in Patient Oriented SCORing Atopic Dermatitis (PO-SCORAD) (40) at week six; difference in Dermatology Life Quality Index (DLQI) (41,42) at week six. Participant acceptability was assessed using Treatment Satisfaction Questionnaire for Medication (TSQM) Version II (43) and Numerical Rating Scale (NRS) of the acceptability of the treatment. Treatment safety was assessed by comparing withdrawals due to eczema exacerbations; requirement for treatment escalation between groups; and proportion of cutaneous and systemic events between treatment groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn exploratory outcome for this study compared the difference in pharmacist-assessed SCORing Atopic Dermatitis (SCORAD) score (part B only) (44). The difference in SCORAD scores was compared between blinded pharmacists, and between blinded pharmacists and remote assessment by a blinded dermatologist.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSample size\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBased on a minimum clinically important difference (MCID) of 3.4\u0026nbsp;(45)\u0026nbsp;and pooled standard deviation (SD) of 6.0\u0026nbsp;(22)\u0026nbsp;for the change in POEM score, each treatment group required 50 participants for 80% power, 5% two-sided alpha. Allowing 15% dropout, 59 participants were required per arm (118 total).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePrimary outcome analysis, and analysis of secondary POEM, PO-SCORAD, and DLQI outcomes were conducted by ANCOVA with baseline scores as continuous covariates, and randomised treatment as a categorical variable of interest. Analysis of TSQM effectiveness dimension was by simple t-test. Due to normality assumptions not being well met (checked by residual distributions and plots of residuals versus predicted values) TSQM side effects, convenience, and global satisfaction dimensions and NRS acceptability were analysed by a Mann-Whitney U test with the Hodges-Lehmann estimator for location difference and appropriate confidence intervals.\u003c/p\u003e\n\u003cp\u003eAnalysis of proportions were by estimation of relative risk and associated confidence intervals. Agreement between pharmacist and dermatologist SCORAD was by linear mixed model, with participant treated as a random effect, and an odds ratio estimating the probability of a higher versus lower rating. Analysis was separated by intention to treat (ITT) and per protocol set (PPS), with ITT as primary analysis. ITT population included all participants randomized. PPS included all participants with at least 80% completed data, including primary outcome, with no significant protocol deviations influencing POEM. For inclusion is PPS, participants were required to adhere to treatment instruction, measured by \u0026gt;80% daily adherence. Missing outcome data were not imputed. SAS software version 9.4 was used for analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRandomisation and masking \u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStudy participants were electronically randomized 1:1 using a block size four, according to a randomisation schedule generated by a blinded biostatistician. Randomisation took place at the pharmacy, and study investigators had no access to the randomisation schedule. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInterventional treatments were labelled by an external compounding pharmacist as \u0026ldquo;Treatment G\u0026rdquo; and \u0026ldquo;Treatment H\u0026rdquo; in non-descript packaging for the purpose of blinding. Study investigators at the pharmacies and MRINZ were blinded. Participants were not told if they received the active or control cream, however the distinctive smell of ECMT-154 was unable to be matched. Therefore, this study will conservatively be classified as single blind rather than double blind, due to high risk for participant unblinding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData Capture\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll study related data, including informed consent, was captured using direct electronic data capture via REDCap electronic data capture tools hosted at MRINZ\u0026nbsp;(46,47). At pharmacy sites, study data was entered using supplied tablet devices. Online study diaries and questionnaires were completed by study participants on their personal devise, accessed through unique links assigned for each time point. Direct electronic data capture enabled real-time data validation through entry range limits, required fields, and logic checks. Study data was securely stored on password-protected servers, accessible only to trial staff and study monitors. Investigators will retain access to the final trial dataset.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMonitoring\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAn independent study monitoring plan was in place to ensure compliance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Good Clinical Practice, and New Zealand ethical guidelines. Any substantial protocol deviations or violations were reported to the New Zealand ethics committee in accordance with approval requirements.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eParticipants were recruited from 20 January 2022 to 22 May 2023 across 11 pharmacies in New Zealand. The final participant follow-up was complete by 19 July 2023. Out of 153 individuals assessed for eligibility, 118 were randomized to 2% ECMT-154 (n=59) or vehicle control (n=59)(Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe participants are described in \u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eBoth groups were well matched in characteristics according to age, sex, and baseline measurements. The study population was primarily female (72%), with a mean (SD) age of 30.35 (11.3). \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"562\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll, n=118\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eECMT-154, n=59\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVehicle control, n=59\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContinuous variables \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 422px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (SD) [range]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eAge (years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e30.4 (11.3)\u003c/p\u003e\n \u003cp\u003e[18-64]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e27.9 (9.8)\u003c/p\u003e\n \u003cp\u003e[18-63]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e32.8 (12.3)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e[18-64]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003ePOEM at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e16.6 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e16.3 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e16.9 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategorical variables\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN/118 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN/59 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN/59 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eFemale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e85 (72.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e40 (67.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e45 (76.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eEthnicity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eAsian\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e12 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e7 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eEuropean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e67 (56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e32 (54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e35 (59.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eMāori\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e26 (22.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e10 (16.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e16 (27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eMELAA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e1 (0.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1 (1.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003ePacific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e4 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e4 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 1. Participant characteristics\u003c/p\u003e\n\u003cp\u003eThere was no evidence of a difference in POEM score at week six between ECMT-154 and vehicle control (p=0.74) (Table 2). Both groups showed mean improvement in POEM score between baseline and week six greater than the pre-defined MCID of 3.4 (8.2 points for EMT-154 and 8.1 points for vehicle control) (Figure 2). Positive \u0026lsquo;responder\u0026rsquo; participants were defined as having an improvement in POEM score of four or more points over the six weeks of study. Both groups had a high proportion of responders to treatment (ECMT-154 = 77.2%, vehicle = 77.4%), however there was no difference between groups (p=0.98). \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eECMT-154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 190px;\"\u003e\n \u003cp\u003eVehicle control\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eMean difference (95% CI) p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eBaseline (n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eWeek 6 ITT\u003c/p\u003e\n \u003cp\u003e(n=57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eWeek 6 PPS\u003c/p\u003e\n \u003cp\u003e(n=24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eBaseline (n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003eWeek 6 ITT\u003c/p\u003e\n \u003cp\u003e(n=53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eWeek 6 PPS\u003c/p\u003e\n \u003cp\u003e(n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eIntention to treat analysis \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003ePer protocol analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePOEM\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e16.3 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e8.1 (6.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e6.75 (5.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e16.9 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e8.8 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e8.40 (6.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e-0.38 (-2.58 to 1.82) p=0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e-0.49 (-3.70 to 2.72) p=0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Data reported as mean (SD) unless otherwise specified. ITT= Intention to treat analysis group. PP = Per protocol analysis group\u003c/p\u003e\n\u003cp\u003eThere was no significant difference in PO-SCORAD between treatment groups at week six (Table 3). The mean (SD) was 23.9 (15.6) for ECMT-154 group and 23.2 (13.7) for the vehicle control group. The mean difference between treatment groups was 0.31 (95% CI -5.05 to 5.67), p=0.91.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mean (SD) change in DLQI scores at week six from baseline was -4.28 for ECMT-154 group and -3.68 for the vehicle control group (Table 3). The mean difference between treatment groups was -0.14 (95% CI -1.74 to 1.47). Although this difference was not significant between groups (p=0.87), the change in DLQI score was larger than the suggested MCID of 4.0 for the ECMT-154 group (48). \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no difference in TSQM-II scores between groups (p=0.66) (Table 3). Both treatment groups had high satisfaction scores in all domains, with particularly high scores in convenience and side effects domains. For overall acceptability NRS, both groups rated study treatment as largely acceptable (Table 3). Median (IQR) for ECMT-154 group was 7 (4 to 9) and 7 (5 to 10) for vehicle control group, p=0.27. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eECMT-154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003eVehicle Control\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eRelative risk (95% CI) p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eBaseline (n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eWeek 6\u003cbr\u003e\u0026nbsp;(n=57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eBaseline (n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWeek 6\u003c/p\u003e\n \u003cp\u003e(n=53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003ePOEM number of responders (N[%])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e44 (77.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e41 (77.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e1.00 (0.81 to 1.22) P=0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 496px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eMean difference (95% CI) p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eSCORAD Part B Dermatologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e4.9 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e3.5 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e4.6 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e3.8 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e-0.50 (-1.30 to 0.31) p=0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003ePO-SCORAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;39.2 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e23.9 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e37.1 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e23.2 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.31 (-5.05 to 5.67) p=0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eDLQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e8.9 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e4.7 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e8.3 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e4.4 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e-0.14 (-1.74 to 1.47) p=0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eTSQM Effectiveness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e55 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e57.7 (27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e-2.73 (-12.24 to 6.78) p=0.57\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 496px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eHodges Lehmann estimator (95% CI) p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eAcceptability NRS (Median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e7 (4 to 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e7 (5 to 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e-1.00 (-2.00 to 0.00) p=0.27\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eTSQM (Median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSide effects\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e100 (100 to 100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e100 (100 to 100)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.00 (0.00 to 0.00) p=0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eConvenience\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e72.2 (61.1 to 83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e72.2 (66.7 to 83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e-5.50 (-11.10 to 0.00) p=0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eGlobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e58.3 (50 to 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e66.7 (33.3 to 83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.00 (-16.60 to 8.30) p=0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. Efficacy and acceptability outcomes. Reported in mean (SD) unless otherwise specified. \u0026nbsp;POEM = Patient Orientated Outcome Measure. PO-SCORAD = Patient Orientated Scoring Atopic Dermatitis. DLQI = Dermatology Life Quality Index. NRS = Numerical Rating Scale. TSQM vII= Treatment Satisfaction Questionnaire for Medication version II.\u003c/p\u003e\n\u003cp\u003eTen total participants discontinued the study intervention due to worsening eczema, treatment side effects, or related adverse events (Table 4). There was no significant difference in the number of withdrawals for worsening eczema between groups; four (6.8%) participants in the ECMT-154 group, and one (1.7%) participant in the vehicle control group (relative risk 3.00, 95% CI 0.32 to 28.02, p=0.31.) There were 18 instances of escalated eczema treatment in the ECMT-154 group (30.5%), and 12 (20.3%) in the vehicle control group (p=0.20). In the ECMT-154 there were 23 related adverse events, compared to 21 in vehicle control group (relative rate 1.10, 95% CI 0.61 to 1.98, p=0.76). Throughout the study only three cases of infective eczema were reported, with two in the ECMT-154 treatment group and one in the vehicle control group. This study provides no evidence to suggest that one treatment group may provide protective effect against infection over the other. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eECMT-154\u003c/p\u003e\n \u003cp\u003e(n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVehicle Control (n=59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eRelative Risk (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eProportion of withdrawal for worsening eczema N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e3 (5.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e3.00 (0.32 to 28.02)\u003c/p\u003e\n \u003cp\u003eP=0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eProportion of treatment escalation* N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e18 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e12 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e1.50 (0.79 to 2.83)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep=0.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eAt least one adverse event N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e45 (76.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e36 (61.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e1.25 (0.97 to 1.60) p=0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eAt least one related adverse event N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e22 (37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e18 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e1.22 (0.74 to 2.03) p=0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003eRelative Rate (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eTotal count of adverse events (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e1.23 (0.87 to 1.75) p=0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eTotal count of related adverse events (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 217px;\"\u003e\n \u003cp\u003e1.10 (0.61 to 1.98 p=0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 4. Safety outcomes. Reported as total count unless otherwise specified. * Experienced an adverse event of worsening eczema that required the use of corticosteroids or antibiotics during the treatment period\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;An exploratory analysis compared the in-person pharmacist and remote dermatologist scoring of eczema severity using SCORAD Part B. Pharmacists were significantly more likely to assign higher scores for oozing, excoriation, lichenification, and ichthyosis at baseline than the dermatologist (p\u0026lt;0.001), and more likely to assign lower baseline scores for swelling (p\u0026lt;0.001) \u0026nbsp;(Table 5). At week six, pharmacists were more likely to assign higher scores for oozing (p=0.002), excoriation, and ichthyosis (p\u0026lt;0.001), and lower scores for erythema and swelling (p\u0026lt;0.001). Acceptability of lesion photographs for scoring judged by the study dermatologist, had a median score of 7 on a 10-point scale. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 481px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePharmacist versus Dermatologist Odds ratio of higher score (95% CI)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eErythema (Redness)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.90 (0.53 to 1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.24 (0.11 to 0.48)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003ePapulation/Oedema (Swelling)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.16 (0.09 to 0.29)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.10 (0.04 to 0.24)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eOozing/crusting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e6.49 (3.21 to 13.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4.92 (1.79 to 13.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eExcoriation (Scratch marks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e16.92 (7.49 to 36.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e9.85 (3.84 to 25.23)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eLichenification (Leathery)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2.93 (1.73 to 4.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1.55 (0.85 to 2.83)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eIchthyosis (Dryness)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e51.57 (17.71 to 150.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e38.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 5. SCORAD (Part B) \u0026nbsp;Inter-rater variability. Pharmacist scoring was conducted in-person. Dermatologist scoring was conducted remotely on a photo of the representative lesion.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis randomised controlled trial has shown no difference in efficacy between\u0026nbsp;2% ECMT-154 and vehicle control cream\u0026nbsp;for the treatment of moderate to severe eczema.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough there was no difference in any outcome measures between groups,\u0026nbsp;both treatment groups reported an improvement in eczema symtpoms, quality of life with positive treatment acceptability ratings. This suggests the vehicle cream to be an effective emollient and demonstrates the benefit of regular emollient use over six weeks (49). There was no statistically significant difference in the rates of adverse events, withdrawals, escalated eczema treatment and study withdrawals for worsening eczema between groups, although a trend in favour of vehicle control was suggested.\u003c/p\u003e\n\u003cp\u003eOutcome measures were selected for this study as recommended by the HOME, which sets recommended outcome measures for clinical trials in eczema (34,37). Some outcomes, such as Eczema Area and Severity Index (EASI)(50) were not able to be implemented for this study due to requirement for full body assessment and limitations to conduct this within a community pharmacy setting.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study had reasonably high external validity as the decentralised study design allowed for recruitment of a generalisable population from diverse ethnic and socioeconomic backgrounds, and various geographical locations throughout New Zealand.\u0026nbsp;Worldwide, there are well documented barriers which impact participation of indigenous populations in clinical trials, contributing to underrepresentation in clinical research (51,52).\u0026nbsp;In this study,\u0026nbsp;22% of participants self-identified as Māori, higher than the 2023 census estimate of 19.6%\u0026nbsp;(53), indicating success of leveraging community-based study sites, and provision of multi-lingual information and consent forms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDue to supply issues in New Zealand, the aqueous cream supplier was changed during the study. Both aqueous creams used were SLS-free. To limit confounding effects, the same number of participants in each treatment group received aqueous cream from\u0026nbsp;Boucher \u0026amp; Muiror (ECMT-154: 24 participants, 40.7%; vehicle control: 24 participants, 40.7%) and Home Essentials (ECMT-154: 35 participants, 59.3%; Vehicle control: 35 participants, 59.3%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was conducted as a double-blind study, and participants were not informed of treatment allocation. However, the distinctive scent of mānuka and palmarosa oil was unable to be matched in the vehicle control.\u0026nbsp;As a result, participants may have been able to infer their treatment allocation, introducing a potential source of bias. For this reason, the study is conservatively reported as single-blind.\u003c/p\u003e\n\u003cp\u003eThe treatment period was limited to six weeks, which is shorter than usual eczema clinical trials. Study duration was selected due to the moderate-to-severe POEM score required by participants, and to minimise the likelihood of participants requiring rescue topical corticosteroids, due to the large impact of these on outcome measures. Assessment over a longer time frame may be beneficial for future research, to evaluate any longer-term remission with use of\u0026nbsp;ECMT-154.\u003c/p\u003e\n\u003cp\u003eThis study also explored the feasibility of pharmacist-led eczema severity scoring with remote dermatologist verification via clinical photographs. There was significant disagreement across most domains (Table 5) and quality of photograph was reported as acceptable in only 72.4%, with 16.3% identified as out of focus, 3.4% with poor lighting, 11.3% too far away from the subject, 1.5% of low image resolution, and 1% poor colour balance. Consistency and quality of clinical photographs is required for remote dermatologist SCORAD scoring, potentially contributing to disagreement in assessment between pharmacists and dermatologist. Furthermore, lack of dermatological expertise appeared to result in higher scoring form most pharmacies assessed domains in SCORAD, similar to finding in our groups previous community-based study of eczema (22). Whilst this teledermatology model has significant potential to facilitate pragmatic trials in the community setting, improved pharmacist training and standardised photography protocols are required for future studies to ensure reliable remote assessment.\u003c/p\u003e\n\u003cp\u003ePrevious research has supported the use of a topical emollient containing 3% kānuka oil for eczema. (22) Mānuka and kānuka are both members of the \u003cem\u003eMyrtaceae\u003c/em\u003e family (54) and have demonstrated similar anti-inflammatory mechanisms in vitro by reducing the production of inflammatory cytokine TNF-\u0026alpha; (23). However, this study identified 2% ECMT-154 does not have similar efficacy in vivo.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe composition and percentage of ECMT-154 used for the study treatment was based on minimum inhibitory concentrations from in vitro experiments. A 2% concentration of ECMT-154 may have been insufficient to achieve an anti-inflammatory effect in vivo, and higher dose may be necessary for potential clinical benefit. However, there was no data trend towards a significant difference, providing no evidence from this study to support this. Only three cases of infective eczema were reported in this study,\u0026nbsp;two in ECMT-154 treatment group and one in vehicle control group. Therefore, whilst both interventions appear to not increase susceptibility toward infection, no analysis was possible to assess antibacterial actions specifically. ECMT-154 is a purified extract comprising primarily the triketone constituents of mānuka oil, excluding other potentially bioactive metabolites. Mānuka oil comprises numerous active compounds, including sesquiterpenes and flavonoids\u0026nbsp;(21,31,55). These other metabolites may contribute the anti-inflammatory effects of mānuka oil\u0026nbsp;(23). The exclusion of non-triketone components in ECMT-154 may disrupt potential synergistic effects necessary for in vivo efficacy.\u003c/p\u003e\n\u003cp\u003eFuture research on optimal concentration of ECMT-154, longer treatment duration or the inclusion of additional bioactive compounds from mānuka could confer any clinical benefit.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion ECMT-154 provided no clinical benefit over vehicle control for the topical treatment of eczema.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eAE Adverse Event\u003cbr\u003eDLQI Dermatology Life Quality Index\u003c/p\u003e\n\u003cp\u003eDSMC Data and Safety Monitoring Committee\u003c/p\u003e\n\u003cp\u003eHDEC Health and Disability Ethics Committee\u003c/p\u003e\n\u003cp\u003eITT Intention-to-treat\u003c/p\u003e\n\u003cp\u003eMCID Minimal Clinically Important Difference\u003c/p\u003e\n\u003cp\u003eNRS Numerical Rating Scale\u003c/p\u003e\n\u003cp\u003ePO-SCORAD Patient-Oriented SCORing Atopic Dermatitis\u003c/p\u003e\n\u003cp\u003ePOEM Patient-Oriented Eczema Measure\u003c/p\u003e\n\u003cp\u003ePPS Per Protocol Set\u003c/p\u003e\n\u003cp\u003eRCT Randomised Controlled Trial\u003c/p\u003e\n\u003cp\u003eSAE Serious Adverse Event\u003c/p\u003e\n\u003cp\u003eSCORAD SCORing Atopic Dermatitis\u003c/p\u003e\n\u003cp\u003eSCOTT Standing Committee on Therapeutic Trials\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by Central Health and Disability Ethics Committee (HDEC reference: 2021 EXP 11490). National Standing Committee on Therapeutic Trials (SCOTT ) approval was obtained (21/SCOTT/118), as required for all clinical trials investigating a new medicine under New Zealand legislation.(56)\u0026nbsp;Electronic written informed consent to participate was obtained from all participants. Conduct of the study was in accordance with guidelines and regulations set forth by HDEC and SCOTT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNarrative feedback obtained from participants who took part in a previous community pharmacy-based study at MRINZ(22,35)\u0026nbsp;informed development of the study protocol and data collection tools.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSH is the inventor of ECMT-154 (as described in International Publication Number WO2022/234340 A1) and a shareholder of Manuka Bioscience. SH was also a contractor (R\u0026amp;D Strategist) at Manuka Bioscience. SH had input into protocol development but was not involved in study conduct or data analysis. AS and GS declare funding from Manuka Bioscience to the MRINZ for the submitted work. There are no other conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial is sponsored and funded by Manuka Biosciences Ltd, who received a Callaghan Innovation Project Grant (MBIOS2003) and R\u0026amp;D Loan (MBIOS2001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was designed by GS, AS, NS, KK, and AE. With later input from MR, and LR. GS and AS are co-chief investigators with overall responsibility for the trial. GS, GB, RB, AM, and AL managed the study participants and data. MR performed remote dermatologist assessment. AE provided statistical analysis. NS built the REDCap trial database. This manuscript was drafted by GS, all authors were involved in manuscript revision and final approval.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all members of the Pharmacy Research Network; Alexander Pharmacy: Angela Liu; Anderson\u0026rsquo;s Exchange Pharmacy: Bob Kim; Castle Chemists: Shahlaa Al Salih; Tamatea Pharmacy: Delwyn Simes and Jenny Motley; Ranolf Pharmacy: Carina Soeteman, Kate Milne, and Manawa Cox; Life Pharmacy Te Puke: Hannah Search and Sally Kim; Life Pharmacy Papakura: Chau Ly and Louise Kim; Life Pharmacy New Plymouth: Nai Yeat; Clive\u0026rsquo;s Chemist: Clive Cannons and Mark Albert\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics and dissemination:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained from Central Health and Disability Ethics Committee on 3\u003csup\u003erd\u003c/sup\u003e December 2021 (reference: 2021 EXP 11490. The Standing Committee on Therapeutic Trails (SCOTT) granted study approval on 20\u003csup\u003eth\u003c/sup\u003e September 2021 (reference: 21/SCOTT/118)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAustralian New Zealand Clinical Trials Registry (ANZCTR)\u0026nbsp;ACTRN12622000684729, the study was registered on 18\u003csup\u003eth\u003c/sup\u003e of August 2021.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eProtocol Version:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e2.1 (Dated 18/05/2022)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJohansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004 May;113(5):832\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eWeidinger S, Novak N. Atopic dermatitis. The Lancet. 2016 Mar 12;387(10023):1109\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eL\u0026uuml;bbe J. Secondary infections in patients with atopic dermatitis. Am J Clin Dermatol. 2003;4(9):641\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eClayton T, Asher MI, Crane J, Ellwood P, Mackay R, Mitchell EA, et al. Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC Phase Three. Asia Pac Allergy. 2013 Jul;3(3):161\u0026ndash;78. \u003c/li\u003e\n\u003cli\u003eOdhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI, ISAAC Phase Three Study Group. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009 Dec;124(6):1251-1258.e23. \u003c/li\u003e\n\u003cli\u003eBuske-Kirschbaum A, Geiben A, Hellhammer D. Psychobiological aspects of atopic dermatitis: an overview. Psychother Psychosom. 2001 Feb;70(1):6\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eKantor R, Silverberg JI. Environmental risk factors and their role in the management of atopic dermatitis. Expert Rev Clin Immunol. 2017 Jan;13(1):15\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eDe Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA. Atopic Dermatitis: A Disease Caused by Innate Immune Defects? Journal of Investigative Dermatology. 2009 Jan 1;129(1):14\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eGeoghegan JA, Irvine AD, Foster TJ. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e and Atopic Dermatitis: A Complex and Evolving Relationship. Trends in Microbiology. 2018 Jun 1;26(6):484\u0026ndash;97. \u003c/li\u003e\n\u003cli\u003eCork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, et al. Epidermal Barrier Dysfunction in Atopic Dermatitis. Journal of Investigative Dermatology. 2009 Aug 1;129(8):1892\u0026ndash;908. \u003c/li\u003e\n\u003cli\u003eLeung DYM. New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation. Allergology International. 2013 Jan 1;62(2):151\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eBos JD, Wierenga EA, Sillevis Smitt JH, van der Heijden FL, Kapsenberg ML. Immune dysregulation in atopic eczema. Arch Dermatol. 1992 Nov;128(11):1509\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eGittler JK, Shemer A, Su\u0026aacute;rez-Fari\u0026ntilde;as M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012 Dec;130(6):1344\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eDubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Review of Clinical Immunology. 2021 Aug 3;17(8):835\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eSimpson EL. Atopic dermatitis: a review of topical treatment options. Current Medical Research and Opinion. 2010;26(3):633\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eChong M, Fonacier L. Treatment of Eczema: Corticosteroids and Beyond. Clinical Reviews in Allergy and Immunology. 2016;51(3):249\u0026ndash;62. \u003c/li\u003e\n\u003cli\u003eLee JH, Son SW, Cho SH. A Comprehensive Review of the Treatment of Atopic Eczema. 2016;8(3):181\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eDiRuggiero D, DiRuggiero M. Beyond Skin Deep: The Systemic Impact of Topical Corticosteroids in Dermatology. J Clin Aesthet Dermatol. 2025;18(1-2 Suppl 1):S16\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eAubert-Wastiaux H, Moret L, Le Rhun A, Fontenoy AM, Nguyen JM, Leux C, et al. Topical corticosteroid phobia in atopic dermatitis: A study of its nature, origins and frequency. British Journal of Dermatology. 2011;165(4):808\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eMathew C, Tesfaye W, Rasmussen P, Peterson GM, Bartholomaeus A, Sharma M, et al. 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Journal of Microbiology, Immunology and Infection. 2016 Feb 1;49(1):104\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eWang J, Su B, Zhu H, Chen C, Zhao G. Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-\u0026kappa;B and p38 MAPK. Exp Ther Med. 2016 Dec;12(6):3607\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003ePrashar A, Hili P, Veness RG, Evans CS. Antimicrobial action of palmarosa oil (Cymbopogon martinii) on Saccharomyces cerevisiae. Phytochemistry. 2003 Jul;63(5):569\u0026ndash;75. \u003c/li\u003e\n\u003cli\u003eDanso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, et al. TNF-\u0026alpha; and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol. 2014 Jul;134(7):1941\u0026ndash;50. \u003c/li\u003e\n\u003cli\u003eHuang Y, Yang XL, Ni YH, Xu ZM. Geraniol suppresses proinflammatory mediators in phorbol 12-myristate 13-acetate with A23187-induced HMC-1 cells. Drug Des Devel Ther. 2018;12:2897\u0026ndash;903. \u003c/li\u003e\n\u003cli\u003eMączka W, Wińska K, Grabarczyk M. One Hundred Faces of Geraniol. Molecules. 2020 Jan;25(14):3303. \u003c/li\u003e\n\u003cli\u003eYe CJ, Li SA, Zhang Y, Lee WH. Geraniol targets KV1.3 ion channel and exhibits anti-inflammatory activity \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e. Fitoterapia. 2019 Nov 1;139:104394. \u003c/li\u003e\n\u003cli\u003eBard M, Albrecht MR, Gupta N, Guynn CJ, Stillwell W. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids. 1988 Jun 1;23(6):534\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eChristoph F, Kaulfers PM, Stahl-Biskup E. A comparative study of the \u003cem\u003ein vitro\u003c/em\u003e antimicrobial activity of tea tree oils s.l. with special reference to the activity of beta-triketones. Planta Med. 2000 Aug;66(6):556\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003evan Klink JW, Larsen L, Perry NB, Weavers RT, Cook GM, Bremer PJ, et al. Triketones active against antibiotic-resistant bacteria: synthesis, structure-activity relationships, and mode of action. Bioorg Med Chem. 2005 Dec 15;13(24):6651\u0026ndash;62. \u003c/li\u003e\n\u003cli\u003eShortt G, Shortt N, Bird G, Kerse K, Lieffering N, Martin A, et al. Mānuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand. BMC Complement Med Ther. 2024 Jan 29;24(1):61. \u003c/li\u003e\n\u003cli\u003eSpuls P i., Gerbens L a. a., Simpson E, Apfelbacher C j., Chalmers J r., Thomas K s., et al. Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement. British Journal of Dermatology. 2017;176(4):979\u0026ndash;84. \u003c/li\u003e\n\u003cli\u003eSemprini A, Singer J, Braithwaite I, Shortt N, Thayabaran D, McConnell M, et al. Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial. BMJ Open. 2019 14;9(5):e026201. \u003c/li\u003e\n\u003cli\u003eSemprini A, Singer J, Shortt N, Braithwaite I, Beasley R. Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting. BMJ Open. 2017 Aug 1;7(8):e017766. \u003c/li\u003e\n\u003cli\u003eSchmitt J, Spuls PI, Thomas KS, Simpson E, Furue M, Deckert S, et al. The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials. J Allergy Clin Immunol. 2014 Oct;134(4):800\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eCharman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients\u0026rsquo; perspective. Arch Dermatol. 2004 Dec;140(12):1513\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eHowells L, Ratib S, Chalmers JR, Bradshaw L, Thomas KS, CLOTHES trial team. How should minimally important change scores for the Patient-Oriented Eczema Measure be interpreted? A validation using varied methods. Br J Dermatol. 2018 May;178(5):1135\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eStalder JF, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, et al. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy. 2011 Aug;66(8):1114\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eFinlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eAli FM, Johns N, Finlay AY, Salek MS, Piguet V. Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index: evidence of equivalence. Br J Dermatol. 2017 Nov;177(5):1306\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eAtkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health. 2005 Dec;8 Suppl 1:S9\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eKunz B, Oranje AP, Labr\u0026egrave;ze L, Stalder JF, Ring J, Ta\u0026iuml;eb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1997;195(1):10\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eSchram ME, Spuls PI, Leeflang MMG, Lindeboom R, Bos JD, Schmitt J. EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important difference. Allergy. 2012 Jan;67(1):99\u0026ndash;106. \u003c/li\u003e\n\u003cli\u003eHarris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics. 2009;42(2):377\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eHarris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O\u0026rsquo;Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019 Jul;95:103208. \u003c/li\u003e\n\u003cli\u003eBasra MKA, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230(1):27\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003evan Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BW. Emollients and moisturisers for eczema. Cochrane Database Syst Rev. 2017 Feb 6;2:CD012119. \u003c/li\u003e\n\u003cli\u003eLeshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol. 2015;172(5):1353\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eGlover M, Kira A, Johnston V, Walker N, Thomas D, Chang AB, et al. A systematic review of barriers and facilitators to participation in randomized controlled trials by Indigenous people from New Zealand, Australia, Canada and the United States. Glob Health Promot. 2015 Mar;22(1):21\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eSchmotzer GL. Barriers and facilitators to participation of minorities in clinical trials. Ethn Dis. 2012;22(2):226\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eStats NZ. 2023 Census population counts (by ethnic group, age, and Māori descent) and dwelling counts [Internet]. 2024 May [cited 2025 Apr 4]. Available from: https://www.stats.govt.nz/information-releases/2023-census-population-counts-by-ethnic-group-age-and-maori-descent-and-dwelling-counts/\u003c/li\u003e\n\u003cli\u003eEssien SO, Baroutian S, Dell K, Young B. Value-added potential of New Zealand mānuka and kānuka products: A review. Industrial Crops and Products. 2019 Apr 1;130:198\u0026ndash;207. \u003c/li\u003e\n\u003cli\u003ePorter NG, Wilkins AL. Chemical, physical and antimicrobial properties of essential oils of \u003cem\u003eLeptospermum scoparium\u003c/em\u003e and \u003cem\u003eKunzea ericoides\u003c/em\u003e. Phytochemistry. 1999 Feb 10;50(3):407\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eMedicines Act 1981 [Internet]. New Zealand Legislation; 2021 Dec [cited 2022 Jun 20]. Report No.: 118. Available from: https://www.legislation.govt.nz/act/public/1981/0118/latest/whole.html#DLM55429\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Eczema, Emollient, Botanical therapy, pharmacy-based research network, Decentralised, Paediatrics, atopic dermatitis","lastPublishedDoi":"10.21203/rs.3.rs-7124892/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7124892/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEczema is a chronic skin condition, characterised by inflammation, erythema, and pruritis. Usage of topical therapies containing botanical extracts is common, however evidence of efficacy is often lacking. This trial investigated the safety and efficacy of a mānuka-oil based cream, 2% ECMT-154, versus vehicle control (VC) for the topical treatment of eczema.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-blind, parallel group randomised controlled trial was undertaken in 11 community pharmacies across New Zealand. Adults with moderate-to-severe eczema (Patient Oriented Eczema Measure [POEM] ≥ 8 to ≤ 24) were randomized 1:1 to topical 2% ECMT-154 or VC cream, applied twice daily for six weeks. The primary outcome was POEM at week six. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e118 participants were recruited between 20\u003csup\u003eth\u003c/sup\u003e January 2022 and 22\u003csup\u003end\u003c/sup\u003e May 2023. Between baseline and week six mean POEM score (standard deviation) improved from 16.3 (4.2) to 8.8 (5.7) in the ECMT-154 group, and from 16.9 (3.8) to 8.8 (5.7) in the VC group, a between group difference of -0.38 (95% CI: -2.58 to 1.82, p=0.74). No statistically significant differences were observed across all secondary outcome measures, and no serious adverse events were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhilst symptoms of eczema improved in both treatment groups, there was no evidence of a difference in efficacy between ECMT-154 and VC cream in the treatment of eczema.\u003c/p\u003e","manuscriptTitle":"Randomised controlled trial of mānuka oil-based ECMT-154™ vs vehicle control for the topical treatment of eczema, conducted in community pharmacies in New Zealand","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-10 09:23:46","doi":"10.21203/rs.3.rs-7124892/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-28T17:21:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-02T09:32:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"142203729185956505048292432881845838858","date":"2025-10-24T14:52:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-20T16:49:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"129827560326324085982715814465597819804","date":"2025-10-19T12:43:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222954355152706178039033840717136296536","date":"2025-09-25T11:22:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-03T02:09:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-07T08:39:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-27T11:54:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-27T11:53:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Complementary Medicine and Therapies","date":"2025-07-15T00:20:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb751530-5e1a-420d-b8ea-0a0c0d3a67ea","owner":[],"postedDate":"September 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-23T09:26:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-10 09:23:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7124892","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7124892","identity":"rs-7124892","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}