Efficacy of Ibuprofen Gargle for Postoperative Pain After Mandibular Third Molar Extraction: A Phase II, Placebo-Controlled, Double-Blind, Randomized Crossover Trial

Abstract BackgroundExtraction of mandibular third molars is one of the most commonly performed oral surgical procedures, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management. Oral administration of NSAIDs produces various adverse events such as gastrointestinal disorders, renal and hepatic dysfunction, and platelet dysfunction. Topical use of analgesics has been proposed as an alternative to oral and injectable medications to safely improve postoperative pain relief. We will conduct a single-center, placebo-controlled, double-blind, randomized crossover trial to assess the pain-relieving effect of an ibuprofen-containing gargle in patients undergoing extraction of mandibular third molars in comparison with a placebo gargle.MethodsThis study will be performed at Kobe University Hospital. Participants (n = 40) will be randomized equally to one of two groups. The IP group will receive ibuprofen gargle on postoperative day (POD) 1 and placebo gargle on POD 2. The PI group will receive placebo gargle on POD 1 and ibuprofen gargle on POD 2. Both groups will receive ibuprofen gargle on PODs 3 to 5 at least once daily. The primary objective is to estimate the within-subject difference in a visual analogue scale (VAS) before and 5 minutes after use of ibuprofen or placebo gargle on PODs 1 and 2. The secondary objectives are to estimate the within-subject difference in ΔVAS before and 15 minutes after use of ibuprofen or placebo gargle on PODs 1 and 2, the ΔVAS before and after 5 or 15 minutes of use of ibuprofen gargle on PODs 3 to 5, the overall effectiveness (self-completion, five scales) on PODs 1 to 5, the daily frequency of use (ibuprofen or placebo gargle and analgesics) on PODs 1 to 7, and the occurrence of adverse events.DiscussionThis will be the first well-designed clinical study to evaluate the efficacy of ibuprofen gargle for relieving postoperative pain after extraction of mandibular third molars. This trial will provide exploratory evidence of the efficacy and safety of ibuprofen gargle for pain reduction after mandibular third molar extraction.Trial registrationJapan Registry of Clinical Trials (jRCT) identifier: jRCTs051210022. Registered on 10 May 2021.