The Comparative Effectiveness of Single versus Double Perclose ProGlide Devices in Achieving Transfemoral AortIc Valve Replacement Access Site Closure: A Prospective, Multicenter, Randomized Controlled Trial (Single-Closure)

The Comparative Effectiveness of Single versus Double Perclose ProGlide Devices in Achieving Transfemoral AortIc Valve Replacement Access Site Closure: A Prospective, Multicenter, Randomized Controlled Trial (Single-Closure) | 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 Study protocol The Comparative Effectiveness of Single versus Double Perclose ProGlide Devices in Achieving Transfemoral AortIc Valve Replacement Access Site Closure: A Prospective, Multicenter, Randomized Controlled Trial (Single-Closure) Jubo Jiang, Lihan Wang, Po Hu, Kaida Ren, Xinping Lin, QiFeng Zhu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5800292/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background The Double Perclose ProGlide™ (Abbott Vascular Devices) is widely adopted device for closing the main arterial access in transfemoral transcatheter aortic valve replacement (TF-TAVR),. Prior studies have compared the single device versus double device approach, but yielding controversial results, highlighting a gap in clinical randomized controlled trials. Trial design This is an investigator-initiated, open-label, multicenter, randomized controlled trial designed to compare the clinical outcomes of single versus double Perclose closure devices. Eligible participants will include patients over 65 years ,with severe aortic stenosis and are indicated for TF-TAVR. These patients will be randomly assigned in a 1:1 ratio to either the single Perclose closure group or the double Perclose closure group. The primary end point of the trial is the rate of access site or access-related major and minor vascular complications,as defined by the VARC-3 criteria. Conclusion This trial aims to compare the clinical outcomes of single versus double Perclose closure. We aim to provide valuable insights into the optimal strategy for large-bore vascular closure in TAVR patients. Perclose ProGlide transcatheter aortic valve replacement transfemoral vascular complications Figures Figure 1 Background Transcatheter aortic valve replacement (TAVR) has been an established treatment option for patients with severe aortic stenosis. It has been proven to be a safe and effective alternative o for patients who are at low, intermediate, and prohibitive risk for surgical valve replacement[ 1 – 8 ]. Access site management is crucial for the success of transfemoral TAVR procedures. Severe vascular complications can result in massive bleeding, necessitate emergency intervention or surgical procedures, and significantly increase the 30-day and 1-year mortality rates[ 9 ]. In recent years, the "preclosure" technique using the Perclose ProGlide system (Abbott Vascular) has emerged as a common approach for vascular closure, deploying sutures prior to arterial site dilation to facilitate post-procedure closure of the large bore arteriotomy site. This technique has been shown to achieve effective hemostasis following a TAVR sheath dilation[ 10 ]. Previous studies have indicated the use of two Perclose devices, or double Perclose closure may reduce vascular complications at the main access site for TAVR patients[ 11 ]. At present, a large number of TAVR centers have adopted this approach for large-bore vascular closure. However, recent clinical practice observations suggest that the use of a single vascular closure device can also effectively achieve vascular closure at the main access site for transfemoral TAVR patients. At the same time, a limited number of studies have compared the efficacy of double versus single Perclose closure through matching analysis[ 12 – 17 ], while the conclusions are controversial. What’s more, these studies are all observational nonrandomized studies, so a direct comparison with one or double vascular closure device is lacking, and potential confounding factors might have influenced the results cannot be ruled out. The single ProGlide approach offers clear advantages, such as lower cost compared to the double ProGlide, and may also result in a shorter procedure time, fewer procedure steps ,reduced stenosis of femoral artery stenosis or a lower risk of failure. This randomized controlled trial aims to compare the clinical outcomes of single versus double Perclose closure. Study objectives and hypotheses This objective of this randomized controlled trial is to assess wether the single Perclose closure is non- inferior to the double Perclose closure for large-bore vascular closure. The primary end point of the trial is the incidence of access site or access-related major and minor vascular complications as defined by the Valve Academic Research Consortium-3 criteria (VARC-3)[ 18 ]. Study design This is an investigator-initiated, open-label, multicenter, randomized controlled trial. The complete clinical trial sites are listed in the protocol Appendix. Patients scheduled to undergo transfemoral TAVR will be randomly assigned to either the single Perclose closure group or the double Perclose closure group at a 1:1 ratio. The Perclose ProGlide system will be used in both groups. Safety and efficacy assessments will be conducted at discharge and 1 month post procedure. An overview of the study flow can be found in Figure 1. The steering committee will be responsible for study design and execution. An independent data and safety monitoring board will review ultimate analysis and safety results. This study will be conducted in compliance with the latest version of the Declaration of Helsinki, the Clinical Trial Agreement and the Clinical Investigation Plan, as well as relevant laws and regulations of China, to ensure the safeguarding of participants’ rights and well-being. Prior to initiation of any protocol beyond standard of care, informed consent will be obtained from each patient, and study participants will have the right to withdraw from the study at any time without cause. Study population and inclusion criteria Eligibility for the study is contingent upon meeting the following criteria: patients must be over 65 years; have severe aortic stenosis; and are indicated for transfemoral TAVR. The primary exclusion criteria include unsuitable vascular access site anatomy for percutaneous vascular closure and any prior the occurrence of vascular access site complications before the TAVR procedure. The selection of potential candidates will be based on the criteria outlined in Table 1. Only those who meet all inclusion criteria and meet none of the exclusion criteria will be enrolled in the study after providing their written informed consent. The CT core laboratory (The Second Affiliated Hospital Zhejiang University School of Medicine) will analyze the CT imaging data of all patients undergoing screening across paticipating centers. Subsequently, the screening committee will evalutate the data to determine the patient eligibility for the study. All symptomatic severe aortic stenosis patients who do not meet the inclusion criteria or decline to participate in the trial will be offered alternative TAVR prostheses or surgical treatment options ,selected to maximize clinical benefit. Blinding and randomization Statistician and participants are blinded to the grouping assignment. Participants under anesthesia during the procedure, and are unaware of the treatment method they received. The statistician responsible for interim analysis and outcome assessment are also blinded,with no access to randomization code nor intraoperative records. Furthermore, the site investigators and follow-up personnel responsible are committed to limiting their involvement in data measurement and analysis, for they are not blind to the treatment allocation. Patients will be randomly assigned to either the single Perclose closure group or the double Perclose closure group in a 1:1 ratio. A stratified block randomization method with a block size of four is utilized, stratified by site. The actual therapeutic plan that patients receive is determined using an interactive voice response system/interactive web response system (IVRS/IWRS). Study device description The Perclose ProGlide™ Suture-Mediated Closure (SMC) System approved for use in China, claims the broadest arterial and venous indication. It can be utilized for 5-21F (Max. 26F OD) arterial sheaths and 5-24F (Max. 29F OD venous sheaths. This Perclose ProStyle Device is composed of a plunger, handle, guide, and sheath. The Perclose™ ProStyle™ Device includes the Perclose™ Suture Trimmer and Perclose™ Snared Knot Pusher ,which are designed to position the pre-tied suture knot at the top of the access site.Additionally, the Perclose ProStyle Suture Trimmer is also designed to trim the trailing limbs of suture beneath the skin. Study procedures In this study, a standardized procedural workflow has been implemented across all participating centers, with comprehensive training provided to minimize outcome variations due to center and operator differences. Each subject will undergo a preoperative MDCT examination to confirm the indication for transfemoral TAVR and to assess the anatomy of the transfemoral access route. The MDCT assessment includes measuring theminimal lumen diameter of the ilio-femoral arteries in two dimensions, identifying the location of the femoral artery bifurcation and evaluating the presence and degree of calcification and tortuosity of the ilio- femoral arteries. The participants will undergo standard TAVR procedure, with puncture of both femoral arteries will be guilded by ultrasound or DSA. Based on the randomization results, each subject will be assigned to either single or double Perclose closure group. After the close of the arteriotomy site, femoral artery angiography will be performed to identify any arterial dissection, arterial stenosis or arterial rupture. Study outcomes The primary end point of the trial is the incidence of access site or access-related major and minor vascular complications as defined by the VARC-3 criteria.(Table2)The secondary end points included the rate of the primary end point at 30 days; components of the primary end point in-hospital and at 30 days; in-hospital and 30-day major and minor vascular complications; unplanned vascular surgery or endovascular interventions at the puncture site; in-hospital and 30-day access site- or access-related bleeding; blood transfusion for access site- or access-related bleeding or vascular complications;the rate of vascular closure devices (VCDs) failure; in-hospital and 30-day all-cause mortality; in-hospital and 30-day mortality attributed to access site or access-related complications; additional unplanned VCDs; time to hemostasis and the length of postprocedural hospital stay. (Table2) Participant follow-up Clinical follow-ups will be performed at one month post-procedure. All efforts will be undertaken to ensure patients’ adherence to the established protocol and attend all scheduled follow-up appointments. The follow-up data from the study participants will be utilized for further subgroup analysis. The timetable for data collection is presented in Table 3. Sample size calculation The primary efficacy endpoint of the study is the rate of access site or access-related major and minor vascular complications as defined by the VARC-3 criteria. Based on the TORCH study (NCT02803294, 2023-10-30) , the composite event rate is estimated to be 9.1% in the double Perclose closure group and 7.1% in the single Perclose closure group. We estimated that a sample of 876 patients (438 patients on each arm) would provide the trial with 80% power to demonstrate the superiority with a superior margin (δ = 0) at a one-sided significance level of 0.025, accounting for an expected 1% dropout rate. The sample size calculation is performed utilizing the SAS® software version 9.4. Planned statistical analyses Continuous variables will be presented as means with standard deviations, medians with inter-quartile ranges or minimum and maximum values. Categorical variables will be reported as frequencies and percentages. The efficacy analysis will be conducted based on the basis of Modified Intention-to-Treat (mITT) and Per Protocol Set (PPS). The mITT set excludes patients who do not undergo the Perclose ProGlide system. The analysis is carried out by the randomized groups, regardless of the actually accepted procedural. All baseline demographic data analysis will be performed on the mITT set. The safety evaluation will be conducted on the Safety Set (SS), including procedural complications, adverse events, and severe adverse events. All summaries and statistical analyses will be generated using SAS® version 9.4 or later. Discussion TAVR is increasingly adopted as a treatment option for patients with severe symptomatic aortic valve stenosis[ 1 , 2 ]. According to the STS-ACC TVT registry[ 19 ], the majority of TAVR procedures are performed via transfemoral (TF) access, which has been associated with reduced bleeding risk, reduced length of stay (LOS), and better rates of discharge to home compared with other access sites. Vascular complications are the most common complications of TF-TAVR and remain a major concern[ 20 ]. Despite advancements in valve design, sheath technology, and VCDs are advancing, vascular complications persist [ 21 , 22 ], with major vascular complications ranging from 15% in high-risk patients[ 9 ] to 2.8%-6% in low- and intermediate- risk patients[ 3 , 5 ]. Vascular complications significantly contribute to both short and long‐term clinical outcomes, including hospital LOS, readmission, need for blood transfusion and all‐cause mortality[ 23 , 24 ]. The suture-mediated percutaneous closure device (PCD) Perclose ProGlide is widely used to achieve hemostasis after TF‐TAVR. A single Perclose closure is indicated to close femoral puncture sites after using up to 8 F sheaths, however, for large‐bore access closure, the double Perclose closure is commonly adopted. The “off‐label” use of a single Perclose closure has already been proposed as possible strategy to achieve hemostasis after TF‐TAVR, and there is scarcityof available data regarding the use of only one Perclose closure[ 12 – 17 ]. In these studies, overall rate of vascular complicationswas 17%[ 16 ], 5%[ 12 ], 8.7%[ 13 , 17 ] and 13.7%[ 14 ]. In the most recent study[ 14 ], the single Perclose closure failure rate was 3.2%, which was consistent with the definitions provided in the last consensus documents[ 18 ], and lower than in previous studies (11%[ 16 ], 5.1%[ 12 ], 75.6%[ 17 ], and 3.9%[ 13 ]). In two studies, the addition of a collagen‐based PCD was the most commonly used immediate “provisional” strategy in the single Perclose closure population in the event of device failure[ 14 , 17 ]. The aforementioned studies are “real-world” and observational nonrandomized studies. Although data of each study was obtained from a prospectively collected database, this represents unspecified single‐arm post hoc analysis: a direct comparison with one or more PCDs is lacking, thus limiting the evaluation of the impact of a single Perclose closure on outcomes. Therefore, potential confounding factors cannot be excluded and may influence the results. To facilitate a comprehensive comparison, we have designed this randomized controlled trial to confirm whether single Perclose closure is non-inferior to double Perclose closure for large bore vascular access following TAVR with regard to safety and efficacy. Our focus will be directed towards meticulous monitoring of access site or access-related major and minor vascular complications. Conclusion This trial aims to compare the clinical effects of single and double Perclose closure. By comparing the outcomes of the single Perclose closure group with those of the double Perclose closure group, this study seeks to provide valuable insights into the optimal strategy for large-bore vascular closure in TAVR patients. The findings of this investigation are anticipated to contribute to clinical outcomes improvement and enhance vascular access management in patients undergoing TAVR. Trial status This trial was initiated on January 23, 2024. And as of November 30, 2024, the study has been initiated at 18 centers, with a total enrollment of 154 patients. Declarations Authors ’ contribution J.J, L.W., P.H. ,and K.R. contributed to the conception and design of the work; X.L., Q.Z., J.F., Y.H., Y.G., Q.L., J.L., H.L., and H.Y. contributed to the acquisition, analysis, and interpretation of data; J.J. drafted the manuscript; J.F., X.L., and J.W. critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy. Funding Not Applicable Data availability statements The data underlying this article will be shared on reasonable request to the corresponding author. Ethical approval and consent to participate All methods were carried out in accordance with the Declaration of Helsinki. The Ethics Review Committee of the Second Affiliated Hospital of Zhejiang University approved the study and written informed consents were obtained from all participants. Consent for publication Not Applicable. Competing interests The authors declare no competing interests. Disclosure All authors declare that there is no conflict of interest relevant to the submitted work. References Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JR, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C et al : 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines . CIRCULATION 2021, 143 (5):e72-e227. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R et al : 2021 ESC/EACTS Guidelines for the management of valvular heart disease . EUR HEART J 2022, 43 (7):561-632. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H et al : Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients . NEW ENGL J MED 2017, 376 (14):1321-1331. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR et al : Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery . NEW ENGL J MED 2010, 363 (17):1597-1607. Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Pibarot P et al : Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients . NEW ENGL J MED 2019, 380 (18):1695-1705. Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O Hair D, Bajwa T, Heiser JC, Merhi W, Kleiman NS et al : Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients . NEW ENGL J MED 2019, 380 (18):1706-1715. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR et al : Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients . NEW ENGL J MED 2011, 364 (23):2187-2198. Yap J, Hayashida K, Lee MKY, Stub D, Hon JKF, Ho KW, Lo S, Seth A, Kim H, Wongpraparut N et al : Asian Pacific Society of Cardiology Position Statement on the Use of Transcatheter Aortic Valve Implantation in the Management of Aortic Stenosis . JACC Asia 2024, 4 (12):885-897. Genereux P, Webb JG, Svensson LG, Kodali SK, Satler LF, Fearon WF, Davidson CJ, Eisenhauer AC, Makkar RR, Bergman GW et al : Vascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial . J AM COLL CARDIOL 2012, 60 (12):1043-1052. Agarwal S, Tuzcu EM, Stewart W, Bajaj NS, Svensson LG, Kapadia SR: Comparison of multicenter registries and randomized control trials for transcatheter aortic valve replacement (TAVR) . INDIAN HEART J 2013, 65 (4):400-411. Griese DP, Reents W, Diegeler A, Kerber S, Babin-Ebell J: Simple, effective and safe vascular access site closure with the double-ProGlide preclose technique in 162 patients receiving transfemoral transcatheter aortic valve implantation . CATHETER CARDIO INTE 2013, 82 (5):E734-E741. Kodama A, Yamamoto M, Shimura T, Kagase A, Koyama Y, Tada N, Takagi K, Araki M, Yamanaka F, Shirai S et al : Comparative data of single versus double proglide vascular preclose technique after percutaneous transfemoral transcatheter aortic valve implantation from the optimized catheter valvular intervention (OCEAN-TAVI) japanese multicenter registry . CATHETER CARDIO INTE 2017, 90 (3):E55-E62. Phan DQ, Qattan M, Lee M, Zadegan R, Mansukhani P, Brar SS, Aharonian V, Moore N: Comparison of a Single Versus Double Perclose Technique for Percutaneous Transfemoral Transcatheter Aortic Valve Replacement . J INVASIVE CARDIOL 2021, 33 (7):E540-E548. Iacovelli F, Burattini O, Sturda F, Branca M, Stabile E, Fimiani L, Salemme L, Cioppa A, Pucciarelli A, Cafaro A et al : Single suture-mediated closure system after transfemoral transcatheter aortic valve implantation: A single-center real-world experience . CATHETER CARDIO INTE 2024, 103 (7):1125-1137. Hollowed J, Akhondi A, Rabbani A, Oncel D, Suh W, Rafique A, Kwon M, Benharash P, Shemin R, Aksoy O: Single versus double Perclose techniques for vascular closure during transfemoral transcatheter aortic valve replacement . CATHETER CARDIO INTE 2022, 99 (7):2125-2130. Kahlert P, Al-Rashid F, Plicht B, Konorza T, Neumann T, Thielmann M, Wendt D, Erbel R, Eggebrecht H: Suture-mediated arterial access site closure after transfemoral aortic valve implantation . CATHETER CARDIO INTE 2013, 81 (2):E139-E150. Bazarbashi N, Ahuja K, Gad MM, Sammour YM, Kaur M, Karrthik A, Saad AM, Khubber S, Dhaliwal K, Mick SL et al : The utilization of single versus double Perclose devices for transfemoral aortic valve replacement access site closure: Insights from Cleveland Clinic Aortic Valve Center . CATHETER CARDIO INTE 2020, 96 (2):442-447. Genereux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, Bax JJ, Leipsic JA, Blanke P, Blackstone EH et al : Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research . EUR HEART J 2021, 42 (19):1825-1857. Carroll JD, Mack MJ, Vemulapalli S, Herrmann HC, Gleason TG, Hanzel G, Deeb GM, Thourani VH, Cohen DJ, Desai N et al : STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement . J AM COLL CARDIOL 2020, 76 (21):2492-2516. Sherwood MW, Xiang K, Matsouaka R, Li Z, Vemulapalli S, Vora AN, Fanaroff A, Harrison JK, Thourani VH, Holmes D et al : Incidence, Temporal Trends, and Associated Outcomes of Vascular and Bleeding Complications in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry . CIRC-CARDIOVASC INTE 2020, 13 (1):e008227. Barbash IM, Barbanti M, Webb J, Molina-Martin De Nicolas J, Abramowitz Y, Latib A, Nguyen C, Deuschl F, Segev A, Sideris K et al : Comparison of vascular closure devices for access site closure after transfemoral aortic valve implantation . EUR HEART J 2015, 36 (47):3370-3379. Sardar MR, Goldsweig AM, Abbott JD, Sharaf BL, Gordon PC, Ehsan A, Aronow HD: Vascular complications associated with transcatheter aortic valve replacement . VASC MED 2017, 22 (3):234-244. Sherwood MW, Xiang K, Matsouaka R, Li Z, Vemulapalli S, Vora AN, Fanaroff A, Harrison JK, Thourani VH, Holmes D et al : Incidence, Temporal Trends, and Associated Outcomes of Vascular and Bleeding Complications in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry . CIRC-CARDIOVASC INTE 2020, 13 (1):e008227. Kawsara A, Sulaiman S, Linderbaum J, Coffey SR, Alqahtani F, Nkomo VT, Crestanello JA, Alkhouli M: Temporal Trends in Resource Use, Cost, and Outcomes of Transcatheter Aortic Valve Replacement in the United States . MAYO CLIN PROC 2020, 95 (12):2665-2673. Tables Table 1. Inclusion and exclusion criteria Inclusion criteria 1. The patient provides consent to participate in the study and commits to the subsequent follow-up assessments. 2. The patient is either aged 65 years or older . 3. The patient has severe aortic stenosis, defined as follows † : Mean gradient across aortic valve ≥40 mm/Hg Or peak aortic jet velocity ≥4.0 m/s Or aortic valve area (AVA) ≤1.0 cm² Or AVA index ≤0.6 cm2 /m2 4. The patient is scheduled to undergo transcatheter aortic valve replacement via transfemoral approach. Exclusion criteria 1. Contraindications to TAVR are present. 2. Surgical aortic valve bioprosthetic valve or TAVR valve degeneration and proposed valve-in-valve 3. Abnormal blood routine: Leukopenia (WBC < 3,000/mm3 ) Or acute anemia (hemoglobin < 9 g/dL) Or thrombocytopenia (PLT < 50,000/mm3 ) Or history of bleeding diathesis or coagulopathy Or hypercoagulable states 4. Active sepsis, including active infective endocarditis, is present. 5. Acute myocardial infarction (AMI) within 1 month prior to the procedure. 6. Stroke or transient ischemic attack (TIA) within 3 months prior to the procedure. 7. Estimated life expectancy of less than 12 months (365 d) due to non-cardiac diseases (such as carcinomas, chronic liver disease, chronic renal disease, or chronic end stage pulmonary disease). 8. Need for emergency surgery for any reason prior to TAVR. 9. Any known hypersensitivity or contraindication to any of the following drugs: aspirin or heparin and bivalirudin; clopidogrel; nitinol; contrast media. 10. Digestive tract bleeding that will limit the use of antithrombotic drugs. 11. Patient refusal of blood transfusion. 12. Severe dementia resulting in the patient’s inability to understand and sign the informed consent form, inability to live independently from care facilities, or inability to complete follow-up visits. 13. The investigator’s conclusion based on other medical, social, and psychological aspects that the patient is not eligible to participate in the study or complete the protocol-specified follow-up visits. 14. Current participation in an investigational drug or device study (excluding registries). Anatomical exclusion criteria 15. Hypertrophic obstructive cardiomyopathy, characterized by myocardial hypertrophy exceeding 1.5 cm without apparent cause. 16. Echocardiographic evidence of intracardiac mass, thrombus, or vegetation. 17. Severe mitral stenosis requiring surgical valve replacement or repair due to organic causes. 18. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick > 5 mm, protruding, or ulcerated), or narrowing of the abdominal or thoracic aorta (especially with calcification and surface irregularities), severe aortic dilatation (ascending aorta > 50 mm), and horizontal ascending aorta (AA > 70°). 19. The vascular characteristics of the main artery and iliofemoral artery that hinder the safe placement of the delivery system include small vascular inner diameter ( 20F. 21. Vascular access site anatomy not suitable for percutaneous vascular closure device. † A low-dose dobutamine stress test is required if the stroke volume index (SVI) is found to be less than 35 mL/m2 . Table 2. Study endpoints of Single-Closure trial Endpoints Content Interpretation Primary endpoint access site or access-related vascular complications in hospital 1. Major vascular complications 2. Minor vascular complications VARC-3 defined Secondary endpoints 1. Incidence of the primary endpoint at 30 days VARC-3 defined 2. Components of the primary end point in-hospital and at 30 days VARC-3 defined 3. Major and minor vascular complications in-hospital and at 30 days VARC-3 defined 4. Unplanned surgery, stent or covered stent implantation, or other endovascular interventional treatments on the main access vessel 5. Access site- or access-related minor, major, disabling or life- threatening bleeding in-hospital and at 30 days VARC-3 defined 6. Blood transfusion for access site or access related bleeding or vascular complications 7. VCD failure The inability to complete hemostasis through manual compression or endovascular balloon compression after the use of vascular closure devices 8. All-cause mortality in-hospital and at 30 days VARC-3 defined 9. Mortality due to access site or access-related complications 10. Unplanned use of additional VCDs 11. Time from VCD application to complete hemostasis 12. Length of post-procedural hospital stay Table 3. Summary of visit schedule and required evaluations Trial process Baseline Procedure Postprocedure 1m follow-up Informed Consent X Demographic data, risk factors/previous medical history X Previous surgical history X Important clinical symptoms X X X Vital signs † X X X Medication record ‡ X X X NYHA classification X X X Surgical risk assessment§ X Blood test# X X X 12-lead ECG∗ X X X Doppler echocardiogram (TTE/TEE)∗ , ∗∗ X X X X Contrast-enhanced CT∗ , †† X X Inclusion and exclusion criteria X Randomized enrollment X Primary endpoints X X Secondary endpoints X X X (Serious) adverse event monitoring and results X X X ∗ The ECG, Doppler echocardiogram and contrast-enhanced CT of the patient at each window should be uploaded to the core laboratory. † Height and weight data should be collected as part of the preoperative vital signs assessment. ‡ The primary cardiovascular medications for patients will be documented in the medication records. Preoperative long-term medical advice will be recorded during the preoperative window period. The drugs prescribed at discharge will be recorded in the window period of discharge or within 7 days post-procedure. Long-term medication for patients on the day of follow-up will be documented in the follow-up window period. § All study participants should undergo evaluation for the Society of Thoracic Surgeons (STS) score, and those between the ages of < 65 and ≥60 years should also be evaluated for other potential contraindications to surgical intervention. # The last preoperative test result is recorded in the baseline window period of blood tests. The last test results during hospitalization are obtained in the window period of discharge or 7 days post procedure. At least one test is required in the other window periods. Baseline test needs to include blood routine (white blood cell count, platelet count, hemoglobin), blood biochemistry (aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, blood creatinine, troponin I/T (preferred) or creatine kinase isoenzyme CK-MB, NTproBNP (preferred) or BNP), coagulation function (prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR)). ∗∗ The CRC is responsible for copying the data source for all ultrasound examinations and uploading them to the core laboratory. The primary endpoint involves data collected 30 days after the procedure, and analysis of the data and issue of the report will be done by the third-party core laboratory. The report from each site will be used for other ultrasound examinations. Prior to the start of the study, there will be uniform training provided. †† All participants should undergo screening with thoracic and abdominal arteriography images or thoracoabdominal artery CT angiography with complete observation of bilateral iliac and femoral arteries up to the aorta. The examination should be performed within 180 days prior to the procedure. A cardiac contrast-enhanced CT reexamination is required 30 days post-procedure to assess valve function. The CRC must copy the data source, upload it to the core laboratory, and issue a report. Additional Declarations No competing interests reported. Supplementary Files SingleClosureprotocol.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 20 Jan, 2025 Editor assigned by journal 17 Jan, 2025 Submission checks completed at journal 17 Jan, 2025 First submitted to journal 09 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5800292","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":403481477,"identity":"be2c79df-3ca2-43f9-b699-ea5bb3cbc5ad","order_by":0,"name":"Jubo Jiang","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jubo","middleName":"","lastName":"Jiang","suffix":""},{"id":403481478,"identity":"c8a798c2-31ca-4579-aad2-9f1a011efb4e","order_by":1,"name":"Lihan Wang","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Lihan","middleName":"","lastName":"Wang","suffix":""},{"id":403481479,"identity":"4b30f9cf-37ee-4860-a993-b5a3d5c6447e","order_by":2,"name":"Po Hu","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Po","middleName":"","lastName":"Hu","suffix":""},{"id":403481480,"identity":"a5551de2-9737-451f-bf1a-e018d361f8b6","order_by":3,"name":"Kaida Ren","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Kaida","middleName":"","lastName":"Ren","suffix":""},{"id":403481481,"identity":"7e307881-a2e0-4dd3-8e1d-34a93a4ccd5e","order_by":4,"name":"Xinping Lin","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xinping","middleName":"","lastName":"Lin","suffix":""},{"id":403481482,"identity":"2b999ee7-56db-488a-9db5-53154cd381ec","order_by":5,"name":"QiFeng Zhu","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"QiFeng","middleName":"","lastName":"Zhu","suffix":""},{"id":403481483,"identity":"e3e16aa8-c632-427c-9465-7d30d85b5ec2","order_by":6,"name":"Jiaqi Fan","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jiaqi","middleName":"","lastName":"Fan","suffix":""},{"id":403481484,"identity":"748f346a-2916-4d33-9ac3-d74425e2bf8e","order_by":7,"name":"Yuxin He","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yuxin","middleName":"","lastName":"He","suffix":""},{"id":403481485,"identity":"5a0ae2a9-454d-4fdf-9843-d06439836f1c","order_by":8,"name":"Yuchao Guo","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yuchao","middleName":"","lastName":"Guo","suffix":""},{"id":403481486,"identity":"0698b490-ceae-4f3c-8d9f-afb2b8677369","order_by":9,"name":"Qiong Liu","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Qiong","middleName":"","lastName":"Liu","suffix":""},{"id":403481487,"identity":"6239d5a2-070d-4c3e-8d29-63585d9f461b","order_by":10,"name":"Jie Liang","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Liang","suffix":""},{"id":403481488,"identity":"88d2858d-46a2-4243-8a2e-620b964255a3","order_by":11,"name":"Huajun Li","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Huajun","middleName":"","lastName":"Li","suffix":""},{"id":403481489,"identity":"fce8d395-f72e-433b-8797-3f677c8eafa2","order_by":12,"name":"Huixiang Yan","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Huixiang","middleName":"","lastName":"Yan","suffix":""},{"id":403481490,"identity":"fe12d08d-2bd0-4f66-a03b-d770a82b6bd2","order_by":13,"name":"Xianbao Liu","email":"","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xianbao","middleName":"","lastName":"Liu","suffix":""},{"id":403481491,"identity":"ed30ae25-e26b-46e6-b120-3f2f35aacb21","order_by":14,"name":"Jian’an Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYLACCQMQydhwIKGCgRksQKQW5sYDD84QqwUC2JsPPmyDmoFPncHxs4dfWBTY5fHPbmw4kDivjt3gAPPB2zwMdnk4tZzJS7OQMEgulrhzEKhlGxuzwQG2ZGsehuRiXFrMDuSYGUgYMCc23EgEaeEBauExk+ZhOJDYgEvL+TcgLfWJ88Fa5kgAtfB/w6/lRo7xAwmDw4kbwFoaDEC2sOHVYn/jjRkwkI8nbgRpSTiWwCx5mM3Yco5BMk4tkv05xp8l/lQnzruR/vjjj5q6ZL7jzQ9vvKmww6kFCNikkaMhGRKZBrjVAwHzxw9IPDu8akfBKBgFo2BEAgCPFlys1IbnPQAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Jian’an","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-01-10 03:53:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5800292/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5800292/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74243446,"identity":"cdf5a7d4-d548-4b05-b733-0348538c3620","added_by":"auto","created_at":"2025-01-20 09:44:13","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241698,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5800292/v1/7e2fd3bbf6de825139419f5a.jpg"},{"id":74247921,"identity":"f47a19ed-0205-43a1-9e6d-928ef34c217f","added_by":"auto","created_at":"2025-01-20 10:08:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2356681,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5800292/v1/52890357-332e-44df-afcf-37de2cb1bdc4.pdf"},{"id":74243448,"identity":"40bb9e6f-9ae6-4377-b21e-c89172a01cc6","added_by":"auto","created_at":"2025-01-20 09:44:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":266498,"visible":true,"origin":"","legend":"","description":"","filename":"SingleClosureprotocol.docx","url":"https://assets-eu.researchsquare.com/files/rs-5800292/v1/1f495ab707e1d84ee4ed3085.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Comparative Effectiveness of Single versus Double Perclose ProGlide Devices in Achieving Transfemoral AortIc Valve Replacement Access Site Closure: A Prospective, Multicenter, Randomized Controlled Trial (Single-Closure)","fulltext":[{"header":"Background","content":"\u003cp\u003eTranscatheter aortic valve replacement (TAVR) has been an established treatment option for patients with severe aortic stenosis. It has been proven to be a safe and effective alternative o for patients who are at low, intermediate, and prohibitive risk for surgical valve replacement[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Access site management is crucial for the success of transfemoral TAVR procedures. Severe vascular complications can result in massive bleeding, necessitate emergency intervention or surgical procedures, and significantly increase the 30-day and 1-year mortality rates[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In recent years, the \"preclosure\" technique using the Perclose ProGlide system (Abbott Vascular) has emerged as a common approach for vascular closure, deploying sutures prior to arterial site dilation to facilitate post-procedure closure of the large bore arteriotomy site. This technique has been shown to achieve effective hemostasis following a TAVR sheath dilation[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Previous studies have indicated the use of two Perclose devices, or double Perclose closure may reduce vascular complications at the main access site for TAVR patients[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. At present, a large number of TAVR centers have adopted this approach for large-bore vascular closure.\u003c/p\u003e \u003cp\u003eHowever, recent clinical practice observations suggest that the use of a single vascular closure device can also effectively achieve vascular closure at the main access site for transfemoral TAVR patients. At the same time, a limited number of studies have compared the efficacy of double versus single Perclose closure through matching analysis[\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], while the conclusions are controversial. What\u0026rsquo;s more, these studies are all observational nonrandomized studies, so a direct comparison with one or double vascular closure device is lacking, and potential confounding factors might have influenced the results cannot be ruled out. The single ProGlide approach offers clear advantages, such as lower cost compared to the double ProGlide, and may also result in a shorter procedure time, fewer procedure steps ,reduced stenosis of femoral artery stenosis or a lower risk of failure. This randomized controlled trial aims to compare the clinical outcomes of single versus double Perclose closure.\u003c/p\u003e\n\u003ch3\u003eStudy objectives and hypotheses\u003c/h3\u003e\n\u003cp\u003eThis objective of this randomized controlled trial is to assess wether the single Perclose closure is non- inferior to the double Perclose closure for large-bore vascular closure. The primary end point of the trial is the incidence of access site or access-related major and minor vascular complications as defined by the Valve Academic Research Consortium-3 criteria (VARC-3)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e "},{"header":"Study design","content":"\u003cp\u003eThis is an investigator-initiated, open-label, multicenter, randomized controlled trial. The complete clinical trial sites are listed in the protocol Appendix. Patients scheduled to undergo transfemoral TAVR will be randomly assigned to either the single Perclose closure group or the double Perclose closure group at a 1:1 ratio. The Perclose ProGlide system will be used in both groups. Safety and efficacy assessments will be conducted at discharge and 1 month post procedure. An overview of the study flow can be found in Figure 1. The steering committee will be responsible for study design and execution. An independent data and safety monitoring board will review ultimate analysis and safety results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study will be conducted in compliance with the latest version of the Declaration of Helsinki, the Clinical Trial Agreement and the Clinical Investigation Plan, as well as relevant laws and regulations of China, to ensure the safeguarding of participants\u0026rsquo; rights and well-being. Prior to initiation of any protocol beyond standard of care, informed consent will be obtained from each patient, and study participants will have the right to withdraw from the study at any time without cause.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population and inclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEligibility for the study is contingent upon meeting the following criteria: patients must be over 65 years; have severe aortic stenosis; and are indicated for transfemoral TAVR. The primary exclusion criteria include unsuitable vascular access site anatomy for percutaneous vascular closure and any prior the occurrence of vascular access site complications before the TAVR procedure. The selection of potential candidates will be based on the criteria outlined in Table 1. Only those who meet all inclusion criteria and meet none of the exclusion criteria will be enrolled in the study after providing their written informed consent.\u003c/p\u003e\n\u003cp\u003eThe CT core laboratory (The Second Affiliated Hospital Zhejiang University School of Medicine) will analyze the CT imaging data of all patients undergoing screening across\u003c/p\u003e\n\u003cp\u003epaticipating centers. Subsequently, the screening committee will evalutate the data to determine the patient eligibility for the study. All symptomatic severe aortic stenosis patients who do not meet the inclusion criteria or decline to participate \u0026nbsp;in the trial will be offered alternative TAVR prostheses or surgical treatment options ,selected to maximize clinical benefit.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlinding and randomization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistician and participants are blinded to the grouping assignment. Participants under anesthesia during the procedure, and are unaware of the treatment method they received. The statistician responsible for interim analysis and outcome assessment are also blinded,with no access to randomization\u003c/p\u003e\n\u003cp\u003ecode nor intraoperative records. Furthermore, the site investigators and follow-up personnel responsible are committed to limiting their involvement in data measurement and analysis, for they are not blind to the treatment allocation.\u003c/p\u003e\n\u003cp\u003ePatients will be randomly assigned to either the single Perclose closure group or the double Perclose closure group in a 1:1 ratio. A stratified block randomization method with a block size of four is utilized, stratified by site. The actual therapeutic plan that patients receive is determined using an interactive voice response system/interactive web response system (IVRS/IWRS).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy device description\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Perclose ProGlide\u0026trade; Suture-Mediated Closure (SMC) System approved for use in China, \u0026nbsp; claims the broadest arterial and venous indication. It can be utilized for 5-21F (Max. 26F OD) arterial sheaths and 5-24F (Max. 29F OD venous sheaths. This Perclose ProStyle Device is composed of a plunger, handle, guide, and sheath. The Perclose\u0026trade; ProStyle\u0026trade; Device includes the Perclose\u0026trade; Suture Trimmer and Perclose\u0026trade; Snared Knot Pusher ,which are designed to position the pre-tied suture knot at the top of the access site.Additionally, the Perclose ProStyle Suture Trimmer is also designed to trim the trailing limbs of suture beneath the skin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy procedures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, a standardized procedural workflow has been implemented across all participating centers, with comprehensive training provided to minimize outcome variations due to center and operator differences. Each subject will undergo a preoperative MDCT examination to confirm the indication for transfemoral TAVR and to assess the anatomy of the transfemoral access route. The MDCT assessment includes measuring theminimal lumen diameter of the ilio-femoral arteries in two dimensions, identifying the location of the femoral artery bifurcation and evaluating the presence and degree of calcification and tortuosity of the ilio- femoral arteries. The participants will undergo standard TAVR procedure, with puncture of both femoral arteries will be guilded by ultrasound or DSA. Based on the randomization results, each subject will be assigned to either single or double Perclose closure group. After the close of the arteriotomy site, femoral artery angiography will be performed to identify any \u0026nbsp;arterial dissection, arterial stenosis or arterial rupture.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary end point of the trial is the incidence of access site or access-related major and minor vascular complications as defined by the VARC-3 criteria.(Table2)The secondary end points included the rate of the primary end point at 30 days; components of the primary end point in-hospital and at 30 days; in-hospital and 30-day major and minor vascular complications; unplanned vascular surgery or endovascular interventions at the puncture site; in-hospital and 30-day access site- or access-related bleeding; blood transfusion for access site- or access-related bleeding or vascular complications;the \u0026nbsp; rate of vascular closure devices (VCDs) failure; in-hospital and 30-day all-cause mortality; in-hospital and 30-day mortality attributed to access site or access-related complications; additional unplanned VCDs; time to hemostasis and the length of postprocedural hospital stay. (Table2)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical follow-ups will be performed at one month post-procedure. All efforts will be undertaken to ensure patients\u0026rsquo; adherence to the established protocol and attend all scheduled follow-up appointments. The follow-up data from the study participants will be utilized for further subgroup analysis. The timetable for data collection is presented in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary efficacy endpoint of the study is the rate of access site or access-related major and minor vascular complications as defined by the VARC-3 criteria. Based on the TORCH study (NCT02803294, 2023-10-30) , the composite event rate is estimated to be 9.1% in the double Perclose closure group and 7.1% in the single Perclose closure group. We estimated that a sample of 876 patients (438 patients on\u003c/p\u003e\n\u003cp\u003eeach arm) would provide the trial with 80% power to demonstrate the superiority with a superior margin (\u0026delta; = 0) at a one-sided significance level of 0.025, accounting for an\u003c/p\u003e\n\u003cp\u003eexpected 1% dropout rate. The sample size calculation is performed utilizing the SAS\u0026reg; software version 9.4.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlanned statistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables will be presented as means with standard deviations, medians with inter-quartile ranges or minimum and maximum values. Categorical variables\u003c/p\u003e\n\u003cp\u003ewill be reported as frequencies and percentages. The efficacy analysis will be conducted \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; based on the basis of Modified Intention-to-Treat (mITT) and Per Protocol Set (PPS). The mITT set excludes patients who do not undergo the Perclose ProGlide system. The analysis is carried out by the randomized groups, regardless of the actually accepted procedural. All baseline demographic data analysis will be performed on the mITT set. The safety evaluation will be conducted on the Safety Set (SS), including procedural complications, adverse events, and severe adverse events. All summaries and statistical analyses will be generated using SAS\u0026reg; version 9.4 or later.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTAVR is increasingly adopted as a treatment option for patients with severe symptomatic aortic valve stenosis[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to the STS-ACC TVT registry[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], the majority of TAVR procedures are performed via transfemoral (TF) access, which has been associated with reduced bleeding risk, reduced length of stay (LOS), and better rates of discharge to home compared with other access sites. Vascular complications are the most common complications of TF-TAVR and remain a major concern[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Despite advancements in valve design, sheath technology, and VCDs are advancing, vascular complications persist [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], with major vascular complications ranging from 15% in high-risk patients[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] to 2.8%-6% in low- and intermediate- risk patients[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Vascular complications significantly contribute to both short and long‐term clinical outcomes, including hospital LOS, readmission, need for blood transfusion and all‐cause mortality[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe suture-mediated percutaneous closure device (PCD) Perclose ProGlide is widely used to achieve hemostasis after TF‐TAVR. A single Perclose closure is indicated to close femoral puncture sites after using up to 8 F sheaths, however, for large‐bore access closure, the double Perclose closure is commonly adopted. The \u0026ldquo;off‐label\u0026rdquo; use of a single Perclose closure has already been proposed as possible strategy to achieve hemostasis after TF‐TAVR, and there is scarcityof available data regarding the use of only one Perclose closure[\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In these studies, overall rate of vascular complicationswas 17%[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], 5%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], 8.7%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and 13.7%[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the most recent study[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], the single Perclose closure failure rate was 3.2%, which was consistent with the definitions provided in the last consensus documents[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and lower than in previous studies (11%[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], 5.1%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], 75.6%[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and 3.9%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]). In two studies, the addition of a collagen‐based PCD was the most commonly used immediate \u0026ldquo;provisional\u0026rdquo; strategy in the single Perclose closure population in the event of device failure[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aforementioned studies are \u0026ldquo;real-world\u0026rdquo; and observational nonrandomized studies. Although data of each study was obtained from a prospectively collected database, this represents unspecified single‐arm post hoc analysis: a direct comparison with one or more PCDs is lacking, thus limiting the evaluation of the impact of a single Perclose closure on outcomes. Therefore, potential confounding factors cannot be excluded and may influence the results. To facilitate a comprehensive comparison, we have designed this randomized controlled trial to confirm whether single Perclose closure is non-inferior to double Perclose closure for large bore vascular access following TAVR with regard to safety and efficacy. Our focus will be directed towards meticulous monitoring of access site or access-related major and minor vascular complications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis trial aims to compare the clinical effects of single and double Perclose closure. By comparing the outcomes of the single Perclose closure group with those of the double Perclose closure group, this study seeks to provide valuable insights into the optimal strategy for large-bore vascular closure in TAVR patients. The findings of this investigation are anticipated to contribute to clinical outcomes improvement and enhance vascular access management in patients undergoing TAVR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial was initiated on January 23, 2024. And as of November 30, 2024, the study has been initiated at 18 centers, with a total enrollment of 154 patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.J, L.W., P.H. ,and K.R. contributed to the conception and design of the work; X.L., Q.Z., J.F., Y.H., Y.G., Q.L., J.L., H.L., and H.Y. contributed to the acquisition, analysis, and interpretation of data; J.J. drafted the manuscript; J.F., X.L., and J.W. critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods were carried out in accordance with the Declaration of Helsinki. The Ethics Review Committee of the Second Affiliated Hospital of Zhejiang University approved the study and written informed consents were obtained from all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there is no conflict of interest relevant to the submitted work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOtto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JR, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003e2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines\u003c/strong\u003e. \u003cem\u003eCIRCULATION\u003c/em\u003e 2021, \u003cstrong\u003e143\u003c/strong\u003e(5):e72-e227.\u003c/li\u003e\n\u003cli\u003eVahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003e2021 ESC/EACTS Guidelines for the management of valvular heart disease\u003c/strong\u003e. \u003cem\u003eEUR HEART J\u003c/em\u003e 2022, \u003cstrong\u003e43\u003c/strong\u003e(7):561-632.\u003c/li\u003e\n\u003cli\u003eReardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, S\u0026oslash;ndergaard L, Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSurgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients\u003c/strong\u003e. \u003cem\u003eNEW ENGL J MED\u003c/em\u003e 2017, \u003cstrong\u003e376\u003c/strong\u003e(14):1321-1331.\u003c/li\u003e\n\u003cli\u003eLeon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eTranscatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery\u003c/strong\u003e. \u003cem\u003eNEW ENGL J MED\u003c/em\u003e 2010, \u003cstrong\u003e363\u003c/strong\u003e(17):1597-1607.\u003c/li\u003e\n\u003cli\u003eMack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Pibarot P\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eTranscatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients\u003c/strong\u003e. \u003cem\u003eNEW ENGL J MED\u003c/em\u003e 2019, \u003cstrong\u003e380\u003c/strong\u003e(18):1695-1705.\u003c/li\u003e\n\u003cli\u003ePopma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O Hair D, Bajwa T, Heiser JC, Merhi W, Kleiman NS\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eTranscatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients\u003c/strong\u003e. \u003cem\u003eNEW ENGL J MED\u003c/em\u003e 2019, \u003cstrong\u003e380\u003c/strong\u003e(18):1706-1715.\u003c/li\u003e\n\u003cli\u003eSmith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eTranscatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients\u003c/strong\u003e. \u003cem\u003eNEW ENGL J MED\u003c/em\u003e 2011, \u003cstrong\u003e364\u003c/strong\u003e(23):2187-2198.\u003c/li\u003e\n\u003cli\u003eYap J, Hayashida K, Lee MKY, Stub D, Hon JKF, Ho KW, Lo S, Seth A, Kim H, Wongpraparut N\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAsian Pacific Society of Cardiology Position Statement on the Use of Transcatheter Aortic Valve Implantation in the Management of Aortic Stenosis\u003c/strong\u003e. \u003cem\u003eJACC Asia\u003c/em\u003e 2024, \u003cstrong\u003e4\u003c/strong\u003e(12):885-897.\u003c/li\u003e\n\u003cli\u003eGenereux P, Webb JG, Svensson LG, Kodali SK, Satler LF, Fearon WF, Davidson CJ, Eisenhauer AC, Makkar RR, Bergman GW\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eVascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial\u003c/strong\u003e. \u003cem\u003eJ AM COLL CARDIOL\u003c/em\u003e 2012, \u003cstrong\u003e60\u003c/strong\u003e(12):1043-1052.\u003c/li\u003e\n\u003cli\u003eAgarwal S, Tuzcu EM, Stewart W, Bajaj NS, Svensson LG, Kapadia SR: \u003cstrong\u003eComparison of multicenter registries and randomized control trials for transcatheter aortic valve replacement (TAVR)\u003c/strong\u003e. \u003cem\u003eINDIAN HEART J\u003c/em\u003e 2013, \u003cstrong\u003e65\u003c/strong\u003e(4):400-411.\u003c/li\u003e\n\u003cli\u003eGriese DP, Reents W, Diegeler A, Kerber S, Babin-Ebell J: \u003cstrong\u003eSimple, effective and safe vascular access site closure with the double-ProGlide preclose technique in 162 patients receiving transfemoral transcatheter aortic valve implantation\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2013, \u003cstrong\u003e82\u003c/strong\u003e(5):E734-E741.\u003c/li\u003e\n\u003cli\u003eKodama A, Yamamoto M, Shimura T, Kagase A, Koyama Y, Tada N, Takagi K, Araki M, Yamanaka F, Shirai S\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eComparative data of single versus double proglide vascular preclose technique after percutaneous transfemoral transcatheter aortic valve implantation from the optimized catheter valvular intervention (OCEAN-TAVI) japanese multicenter registry\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2017, \u003cstrong\u003e90\u003c/strong\u003e(3):E55-E62.\u003c/li\u003e\n\u003cli\u003ePhan DQ, Qattan M, Lee M, Zadegan R, Mansukhani P, Brar SS, Aharonian V, Moore N: \u003cstrong\u003eComparison of a Single Versus Double Perclose Technique for Percutaneous Transfemoral Transcatheter Aortic Valve Replacement\u003c/strong\u003e. \u003cem\u003eJ INVASIVE CARDIOL\u003c/em\u003e 2021, \u003cstrong\u003e33\u003c/strong\u003e(7):E540-E548.\u003c/li\u003e\n\u003cli\u003eIacovelli F, Burattini O, Sturda F, Branca M, Stabile E, Fimiani L, Salemme L, Cioppa A, Pucciarelli A, Cafaro A\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSingle suture-mediated closure system after transfemoral transcatheter aortic valve implantation: A single-center real-world experience\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2024, \u003cstrong\u003e103\u003c/strong\u003e(7):1125-1137.\u003c/li\u003e\n\u003cli\u003eHollowed J, Akhondi A, Rabbani A, Oncel D, Suh W, Rafique A, Kwon M, Benharash P, Shemin R, Aksoy O: \u003cstrong\u003eSingle versus double Perclose techniques for vascular closure during transfemoral transcatheter aortic valve replacement\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2022, \u003cstrong\u003e99\u003c/strong\u003e(7):2125-2130.\u003c/li\u003e\n\u003cli\u003eKahlert P, Al-Rashid F, Plicht B, Konorza T, Neumann T, Thielmann M, Wendt D, Erbel R, Eggebrecht H: \u003cstrong\u003eSuture-mediated arterial access site closure after transfemoral aortic valve implantation\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2013, \u003cstrong\u003e81\u003c/strong\u003e(2):E139-E150.\u003c/li\u003e\n\u003cli\u003eBazarbashi N, Ahuja K, Gad MM, Sammour YM, Kaur M, Karrthik A, Saad AM, Khubber S, Dhaliwal K, Mick SL\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eThe utilization of single versus double Perclose devices for transfemoral aortic valve replacement access site closure: Insights from Cleveland Clinic Aortic Valve Center\u003c/strong\u003e. \u003cem\u003eCATHETER CARDIO INTE\u003c/em\u003e 2020, \u003cstrong\u003e96\u003c/strong\u003e(2):442-447.\u003c/li\u003e\n\u003cli\u003eGenereux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, Bax JJ, Leipsic JA, Blanke P, Blackstone EH\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eValve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research\u003c/strong\u003e. \u003cem\u003eEUR HEART J\u003c/em\u003e 2021, \u003cstrong\u003e42\u003c/strong\u003e(19):1825-1857.\u003c/li\u003e\n\u003cli\u003eCarroll JD, Mack MJ, Vemulapalli S, Herrmann HC, Gleason TG, Hanzel G, Deeb GM, Thourani VH, Cohen DJ, Desai N\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSTS-ACC TVT Registry of Transcatheter Aortic Valve Replacement\u003c/strong\u003e. \u003cem\u003eJ AM COLL CARDIOL\u003c/em\u003e 2020, \u003cstrong\u003e76\u003c/strong\u003e(21):2492-2516.\u003c/li\u003e\n\u003cli\u003eSherwood MW, Xiang K, Matsouaka R, Li Z, Vemulapalli S, Vora AN, Fanaroff A, Harrison JK, Thourani VH, Holmes D\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eIncidence, Temporal Trends, and Associated Outcomes of Vascular and Bleeding Complications in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry\u003c/strong\u003e. \u003cem\u003eCIRC-CARDIOVASC INTE\u003c/em\u003e 2020, \u003cstrong\u003e13\u003c/strong\u003e(1):e008227.\u003c/li\u003e\n\u003cli\u003eBarbash IM, Barbanti M, Webb J, Molina-Martin De Nicolas J, Abramowitz Y, Latib A, Nguyen C, Deuschl F, Segev A, Sideris K\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eComparison of vascular closure devices for access site closure after transfemoral aortic valve implantation\u003c/strong\u003e. \u003cem\u003eEUR HEART J\u003c/em\u003e 2015, \u003cstrong\u003e36\u003c/strong\u003e(47):3370-3379.\u003c/li\u003e\n\u003cli\u003eSardar MR, Goldsweig AM, Abbott JD, Sharaf BL, Gordon PC, Ehsan A, Aronow HD: \u003cstrong\u003eVascular complications associated with transcatheter aortic valve replacement\u003c/strong\u003e. \u003cem\u003eVASC MED\u003c/em\u003e 2017, \u003cstrong\u003e22\u003c/strong\u003e(3):234-244.\u003c/li\u003e\n\u003cli\u003eSherwood MW, Xiang K, Matsouaka R, Li Z, Vemulapalli S, Vora AN, Fanaroff A, Harrison JK, Thourani VH, Holmes D\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eIncidence, Temporal Trends, and Associated Outcomes of Vascular and Bleeding Complications in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Insights From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry\u003c/strong\u003e. \u003cem\u003eCIRC-CARDIOVASC INTE\u003c/em\u003e 2020, \u003cstrong\u003e13\u003c/strong\u003e(1):e008227.\u003c/li\u003e\n\u003cli\u003eKawsara A, Sulaiman S, Linderbaum J, Coffey SR, Alqahtani F, Nkomo VT, Crestanello JA, Alkhouli M: \u003cstrong\u003eTemporal Trends in Resource Use, Cost, and Outcomes of Transcatheter Aortic Valve Replacement in the United States\u003c/strong\u003e. \u003cem\u003eMAYO CLIN PROC\u003c/em\u003e 2020, \u003cstrong\u003e95\u003c/strong\u003e(12):2665-2673.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eInclusion\u0026nbsp;and\u0026nbsp;exclusion\u0026nbsp;criteria\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"638\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInclusion\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ecriteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1.\u0026nbsp;The\u0026nbsp;patient\u0026nbsp;provides\u0026nbsp;consent\u0026nbsp;to\u0026nbsp;participate\u0026nbsp;in\u0026nbsp;the\u0026nbsp;study\u0026nbsp;and\u0026nbsp;commits\u0026nbsp;to\u0026nbsp;the\u0026nbsp;subsequent\u0026nbsp;follow-up assessments.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. The patient is either aged 65 years or older\u0026nbsp;.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e3. The patient has severe aortic stenosis, defined as follows\u003cem\u003e\u0026dagger;\u0026nbsp;\u003c/em\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eMean gradient across aortic valve \u0026ge;40 mm/Hg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr peak aortic jet velocity \u0026ge;4.0 m/s\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr aortic valve area (AVA) \u0026le;1.0 cm\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr AVA index \u0026le;0.6 cm2 /m2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e4. The patient is scheduled to undergo transcatheter aortic valve replacement via transfemoral approach.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExclusion\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;criteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1. Contraindications to TAVR\u0026nbsp;are present.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. Surgical aortic valve bioprosthetic valve or TAVR valve degeneration and proposed valve-in-valve\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e3. Abnormal blood routine:\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eLeukopenia (WBC \u003cem\u003e\u0026lt;\u003c/em\u003e3,000/mm3 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr acute anemia (hemoglobin \u003cem\u003e\u0026lt;\u003c/em\u003e9 g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr thrombocytopenia (PLT \u003cem\u003e\u0026lt;\u003c/em\u003e50,000/mm3 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr\u0026nbsp;history\u0026nbsp;of\u0026nbsp;bleeding\u0026nbsp;diathesis\u0026nbsp;or coagulopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003eOr\u0026nbsp;hypercoagulable states\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e4. Active sepsis, including active infective endocarditis, is present.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e5. Acute myocardial infarction (AMI) within 1 month\u0026nbsp;prior to the procedure.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e6. Stroke or transient ischemic attack (TIA) within 3 months\u0026nbsp;prior to the procedure.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e7. Estimated life expectancy of less than 12 months\u0026nbsp;(365 d) due to non-cardiac diseases (such as carcinomas, chronic liver disease, chronic renal\u003c/p\u003e\n \u003cp\u003edisease,\u0026nbsp;or\u0026nbsp;chronic\u0026nbsp;end\u0026nbsp;stage\u0026nbsp;pulmonary disease).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e8. Need for emergency surgery for any reason prior to TAVR.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e9. Any known hypersensitivity or contraindication to any of the following drugs: aspirin or heparin and bivalirudin; clopidogrel; nitinol; contrast\u003c/p\u003e\n \u003cp\u003emedia.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e10. Digestive tract bleeding that will limit the use of antithrombotic drugs.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e11. Patient refusal of blood transfusion.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e12. Severe dementia resulting in the patient\u0026rsquo;s inability to understand and sign the informed consent form, inability to live independently from care\u003c/p\u003e\n \u003cp\u003efacilities,\u0026nbsp;or\u0026nbsp;inability\u0026nbsp;to\u0026nbsp;complete\u0026nbsp;follow-up visits.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e13. The investigator\u0026rsquo;s conclusion based on other medical, social, and psychological aspects that the patient is not eligible to participate in the\u003c/p\u003e\n \u003cp\u003estudy\u0026nbsp;or\u0026nbsp;complete\u0026nbsp;the\u0026nbsp;protocol-specified\u0026nbsp;follow-up visits.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e14. Current participation in an investigational drug or device study (excluding registries).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnatomical\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eexclusion\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ecriteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e15. Hypertrophic obstructive cardiomyopathy, characterized by myocardial hypertrophy exceeding 1.5 cm without apparent cause.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e16. Echocardiographic evidence of intracardiac mass, thrombus, or vegetation.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e17. Severe mitral stenosis requiring surgical valve replacement or repair due to organic causes.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e18. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick \u003cem\u003e\u0026gt;\u003c/em\u003e5 mm, protruding, or ulcerated), or narrowing of the abdominal or thoracic aorta (especially with calcification and surface irregularities), severe aortic dilatation\u003c/p\u003e\n \u003cp\u003e(ascending aorta \u003cem\u003e\u0026gt;\u003c/em\u003e50 mm), and horizontal ascending aorta (AA \u003cem\u003e\u0026gt;\u003c/em\u003e70\u0026deg;).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e19. The vascular characteristics of the main artery and iliofemoral artery that hinder the safe placement of the delivery system include small vascular inner diameter (\u0026lt; 6mm), vascular dissection, significant vascular distortion, severe calcification, etc.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e20. The main approach of femoral artery implantation with a large sheath inner diameter \u0026gt; 20F.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e21.\u0026nbsp;Vascular access site anatomy not suitable for percutaneous vascular closure device.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026dagger;\u0026nbsp;\u003c/em\u003eA low-dose dobutamine stress test is required if the stroke volume index (SVI) is found to be less than 35 mL/m2 .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eStudy\u0026nbsp;endpoints\u0026nbsp;of\u0026nbsp;Single-Closure trial\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eEndpoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003eContent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eInterpretation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003ePrimary endpoint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\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: 115px;\"\u003e\n \u003cp\u003eaccess site or access-related vascular complications\u0026nbsp;in hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1. Major vascular complications\u003c/p\u003e\n \u003cp\u003e2. Minor vascular complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eSecondary endpoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e1. Incidence of the primary endpoint at 30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e2.\u0026nbsp;Components of the primary end point in-hospital and at 30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e3.\u0026nbsp;Major and minor vascular complications in-hospital and at 30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e4.\u0026nbsp;Unplanned surgery, stent or covered stent implantation, or other endovascular interventional treatments on the main access vessel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e5.\u0026nbsp;Access site- or access-related minor, major, disabling or life- threatening bleeding in-hospital and at 30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e6.\u0026nbsp;Blood transfusion for access site or access related bleeding or vascular complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\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: 265px;\"\u003e\n \u003cp\u003e7. VCD failure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eThe inability to complete hemostasis through manual compression or endovascular balloon compression after the use of vascular closure devices\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e8.\u0026nbsp;All-cause mortality in-hospital and at 30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003eVARC-3 defined\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 265px;\"\u003e\n \u003cp\u003e9. Mortality due to access site or access-related complications\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\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: 265px;\"\u003e\n \u003cp\u003e10. Unplanned use of additional VCDs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\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: 265px;\"\u003e\n \u003cp\u003e11.\u0026nbsp;Time from VCD application to complete hemostasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\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: 265px;\"\u003e\n \u003cp\u003e12.\u0026nbsp;Length of post-procedural hospital stay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 166px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eSummary of visit schedule and required evaluations\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"524\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eTrial process\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eProcedure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003ePostprocedure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e1m follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eInformed Consent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003eDemographic\u0026nbsp;data, risk\u003c/p\u003e\n \u003cp\u003efactors/previous\u0026nbsp;medical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003ePrevious\u0026nbsp;surgical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003eImportant\u0026nbsp;clinical symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eVital signs\u003cem\u003e\u0026dagger;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eMedication record\u003cem\u003e\u0026Dagger;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eNYHA classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eSurgical risk assessment\u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003eBlood test#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e12-lead ECG\u0026lowast;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eDoppler echocardiogram\u003c/p\u003e\n \u003cp\u003e(TTE/TEE)\u0026lowast; , \u0026lowast;\u0026lowast;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eContrast-enhanced CT\u0026lowast; , \u003cem\u003e\u0026dagger;\u0026dagger;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eInclusion and exclusion criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003eRandomized enrollment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\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: 161px;\"\u003e\n \u003cp\u003ePrimary endpoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eSecondary endpoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e(Serious)\u0026nbsp;adverse\u0026nbsp;event monitoring\u003c/p\u003e\n \u003cp\u003eand results\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026lowast;\u0026nbsp;The ECG, Doppler echocardiogram and contrast-enhanced CT of the patient at each window should be uploaded to the core laboratory.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026dagger;\u0026nbsp;\u003c/em\u003eHeight and weight data should be collected as part of the preoperative vital signs assessment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026Dagger;\u0026nbsp;\u003c/em\u003eThe primary cardiovascular medications for patients will be documented in the medication records. Preoperative long-term medical advice will \u0026nbsp;be recorded during the preoperative window period. The drugs prescribed at discharge will be recorded in the window period of discharge or within 7 days post-procedure. Long-term medication for patients on the day of follow-up will be documented in the follow-up window period.\u003c/p\u003e\n\u003cp\u003e\u0026sect; All study participants should undergo evaluation for the Society of Thoracic Surgeons (STS) score, and those between the ages of \u003cem\u003e\u0026lt;\u003c/em\u003e65 and \u0026ge;60 years should also be evaluated for other potential contraindications to surgical intervention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e# The last preoperative test result is recorded in the baseline window period of blood tests. The last test results during hospitalization are obtained in the window period of discharge or 7 days post procedure. At least one test is required in the other window periods. Baseline test needs to include blood routine (white blood cell count, platelet count, hemoglobin), blood biochemistry (aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, blood creatinine, troponin I/T (preferred) or creatine kinase isoenzyme CK-MB, NTproBNP (preferred) or BNP), coagulation function (prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR)).\u003c/p\u003e\n\u003cp\u003e\u0026lowast;\u0026lowast; The CRC is responsible for copying the data source for all ultrasound examinations and uploading them to the core laboratory. The primary endpoint involves data\u0026nbsp;collected 30 days after the procedure, and analysis of the data and issue of the report will be done by the third-party core laboratory. The report from each site will be used for other ultrasound examinations. Prior to the start of the study, there will be uniform training provided.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026dagger;\u0026dagger;\u0026nbsp;\u003c/em\u003eAll participants should undergo screening with thoracic and abdominal arteriography images or thoracoabdominal artery CT angiography with complete observation of bilateral iliac and femoral arteries up to the aorta. The examination should be performed within 180 days prior to the procedure. A cardiac contrast-enhanced CT reexamination is required 30 days post-procedure to assess valve function. The CRC must copy the data source, upload it to the core laboratory, and issue a report.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Perclose ProGlide, transcatheter aortic valve replacement, transfemoral, vascular complications","lastPublishedDoi":"10.21203/rs.3.rs-5800292/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5800292/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe Double Perclose ProGlide\u0026trade; (Abbott Vascular Devices) is widely adopted device for closing the main arterial access in transfemoral transcatheter aortic valve replacement (TF-TAVR),. Prior studies have compared the single device versus double device approach, but yielding controversial results, highlighting a gap in clinical randomized controlled trials.\u003c/p\u003e\u003ch2\u003eTrial design\u003c/h2\u003e \u003cp\u003eThis is an investigator-initiated, open-label, multicenter, randomized controlled trial designed to compare the clinical outcomes of single versus double Perclose closure devices. Eligible participants will include patients over 65 years ,with severe aortic stenosis and are indicated for TF-TAVR. These patients will be randomly assigned in a 1:1 ratio to either the single Perclose closure group or the double Perclose closure group. The primary end point of the trial is the rate of access site or access-related major and minor vascular complications,as defined by the VARC-3 criteria.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis trial aims to compare the clinical outcomes of single versus double Perclose closure. We aim to provide valuable insights into the optimal strategy for large-bore vascular closure in TAVR patients.\u003c/p\u003e","manuscriptTitle":"The Comparative Effectiveness of Single versus Double Perclose ProGlide Devices in Achieving Transfemoral AortIc Valve Replacement Access Site Closure: A Prospective, Multicenter, Randomized Controlled Trial (Single-Closure)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-20 09:44:08","doi":"10.21203/rs.3.rs-5800292/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-20T09:42:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-17T11:10:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-17T11:08:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-01-10T03:42:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e9b77959-c095-435a-a45d-441659c0f9a8","owner":[],"postedDate":"January 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-01-24T01:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-20 09:44:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5800292","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5800292","identity":"rs-5800292","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}