Daré Bioscience, Inc., San Diego, California; the University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, Pennsylvania; Gendreau Consulting, LLC, Poway, California; Health Decisions, Inc., Durham, North Carolina; Segal Trials and the University of Miami Miller School of Medicine, Miami, Florida; Precision Trials AZ, LLC, Phoenix, Arizona; Praetorian Pharmaceutical Research and West Jefferson Medical Center, Marrero, Louisiana; Southern Clinical Research Associates, LLC, Metairie, Louisiana; and TMC Life Research, Inc., Houston, Texas.
Obstet Gynecol. 2022 Jun 1;139(6):1092-1102. doi: 10.1097/AOG.0000000000004805. Epub 2022 May 2.
To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment.
We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed).
Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis.
A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry.
The study was funded by Daré Bioscience, Inc.
ClinicalTrials.gov, NCT04370548.
评估单剂量阴道克林霉素凝胶治疗细菌性阴道病的疗效和安全性。
我们进行了一项双盲、安慰剂对照、随机研究，比较克林霉素凝胶与安慰剂（2:1 比例）。入组需要细菌性阴道病的临床诊断，即所有四项 Amsel 标准，无其他生殖器感染。根据 2019 年美国食品和药物管理局的最新指导意见，需要 Nugent 评分 7-10 进行疗效评估。患者在筛查、第 7-14 天和第 21-30 天（治疗后评估）进行评估。临床治愈定义为四项 Amsel 标准中的三项得到解决。细菌学治愈定义为 Nugent 评分低于 4 分。治疗治愈是指临床和细菌学治愈。主要结局是治疗后评估时的临床治愈。次要终点是第 7-14 天的临床治愈，以及第 7-14 天和治疗后评估的细菌学和治疗学治愈。克林霉素组 188 例患者和安慰剂组 94 例患者的样本量具有 90%的统计学效力，可检测到有统计学意义的差异（P=.05，双尾）。
参与者于 2020 年 7 月 9 日至 2020 年 11 月 12 日接受了治疗。在 307 名随机女性中，56.0%为黑人，88.3%报告有一次或多次细菌性阴道病发作。在改良意向治疗人群中，克林霉素组 70.5%和安慰剂组 35.6%的患者在治疗后评估时达到临床治愈（主要结局）（差异为 34.9，95%CI 19.0-50.8），克林霉素组 77.5%和安慰剂组 42.6%的患者在方案人群中达到临床治愈（差异为 34.9，95%CI 17.0-52.7）。所有次要终点均显示组间存在统计学显著差异。克林霉素组中过去一年细菌性阴道病发作次数多于三次的患者临床治愈率为 70.0%。克林霉素组约有 15%（15.3%）的患者出现 1 次或多次与研究治疗相关的治疗中出现的不良事件，安慰剂组中有 9.7%的患者出现这种情况。最常见的与治疗相关的治疗中出现的不良事件是外阴阴道念珠菌病。
新的单剂量克林霉素阴道凝胶在受细菌性阴道病影响不成比例的女性中非常有效，安全性良好，研究入组时 Nugent 评分为 7-10。
该研究由 Daré Bioscience， Inc. 资助。
ClinicalTrials.gov，NCT04370548。
