Hillier Sharon L, Nyirjesy Paul, Waldbaum Arthur S, Schwebke Jane R, Morgan Franklin G, Adetoro Nikki A, Braun Carol J
University of Pittsburgh and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania; Drexel University School of Medicine, Philadelphia, Pennsylvania; Downtown Women's Health Care, Denver, Colorado; the University of Alabama at Birmingham, Birmingham, Alabama; Tidewater Clinical Research, Inc, Virginia Beach, Virginia; and Symbiomix Therapeutics, LLC, and SAJE Consulting LLC, Baltimore, Maryland.
Obstet Gynecol. 2017 Aug;130(2):379-386. doi: 10.1097/AOG.0000000000002135.
To evaluate secnidazole as a single oral dose treatment for bacterial vaginosis in a phase 2 randomized, double-blind, placebo-controlled study.
In a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study, women with bacterial vaginosis who met all Amsel criteria (discharge; pH 4.7 or greater; 20% or greater clue cells; positive whiff test) were randomized one to one to one at 24 U.S. centers to 1 or 2 g secnidazole compared with placebo. The primary endpoint was clinical cure (normalization of discharge, amine odor, and clue cells) 21-30 days after treatment. Secondary endpoints included microbiologic cure, defined as a Nugent score of 0-3, and therapeutic cure, defined as meeting criteria for both clinical and microbiologic cure. The modified intent to treat was used for efficacy analyses and included all randomized patients who met the enrollment criteria. Assuming a clinical cure rate of 40% in the active groups and 15% in the placebo group, a sample size of 52 patients per group provided approximately 80% power to detect a significant difference between groups (.05 level [two-sided]) using a Cochran-Mantel-Haenszel test.
Between May and September 2014, 215 patients were enrolled. In the intent-to-treat population, the clinical cure rate was 65.3% for the 2-g group, 49.3% for the 1-g group, and 19.4% for the placebo group. The modified intent-to-treat population included 188 women (median age 33 years; 32% with four or more bacterial vaginosis episodes in the previous year; 54% black) with baseline Nugent scores 4 or greater. Clinical, microbiologic, and therapeutic cure rates were 67.7%, 40.3%, and 40.3% for 2 g secnidazole and 51.6%, 23.4%, and 21.9% for 1 g secnidazole compared with 17.7%, 6.5%, and 6.5% for placebo, respectively (P<.05 for secnidazole compared with placebo; all endpoints). Both doses were well-tolerated.
Oral granules containing 1 and 2 g secnidazole were superior to placebo in bacterial vaginosis treatment (P<.001 for both groups). These data support the development of secnidazole for bacterial vaginosis treatment.
ClinicalTrials.gov, NCT02147899.
在一项2期随机、双盲、安慰剂对照研究中评估塞克硝唑单剂量口服治疗细菌性阴道病的效果。
在一项2期随机、双盲、剂量范围研究、安慰剂对照研究中，符合所有阿姆塞尔标准（白带；pH值4.7或更高；线索细胞20%或更多；嗅味试验阳性）的细菌性阴道病女性患者在美国24个中心按1:1:1随机分组，分别给予1或2克塞克硝唑，与安慰剂进行比较。主要终点是治疗后21 - 30天的临床治愈（白带、胺味和线索细胞恢复正常）。次要终点包括微生物学治愈，定义为 Nugent 评分为0 - 3，以及治疗性治愈，定义为符合临床和微生物学治愈标准。改良意向性分析用于疗效分析，包括所有符合入组标准的随机分组患者。假设活性组的临床治愈率为40%，安慰剂组为15%，每组52例患者的样本量使用 Cochr an - Mantel - Haenszel 检验能提供约80%的检验效能来检测组间显著差异（双侧α = 0.05水平）。
2014年5月至9月期间，共纳入215例患者。在意向性分析人群中，2克组临床治愈率为65.3%，1克组为49.3%，安慰剂组为19.4%。改良意向性分析人群包括188名女性（中位年龄33岁；32%在前一年有四次或更多次细菌性阴道病发作；54%为黑人），基线 Nugent 评分4或更高。2克塞克硝唑组的临床、微生物学和治疗性治愈率分别为67.7%、40.3%和40.3%，1克塞克硝唑组分别为51.6%、23.4%和21.9%，而安慰剂组分别为17.7%、6.5%和6.5%（塞克硝唑与安慰剂相比，所有终点P < 0.05）。两种剂量耐受性均良好。
含1克和2克塞克硝唑的口服颗粒剂在治疗细菌性阴道病方面优于安慰剂（两组P < 0.001）。这些数据支持塞克硝唑用于治疗细菌性阴道病的研发。
ClinicalTrials.gov，NCT02147899 。
