Randomized trial of multi-strain Lactobacillus crispatus vaginal live biotherapeutic products after antibiotic therapy for bacterial vaginosis: study protocol for VIBRANT (vaginal lIve biotherapeutic RANdomized trial)

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary Clinical Trials Communications Pub Date : 2025-09-16 DOI:10.1016/j.conctc.2025.101554

Callin Chetty , Nomfuneko Mafunda , Anna-Ursula Happel , Anam Khan , Briah Cooley Demidkina , Nonhlanhla Yende-Zuma , Yusra Saidi , Asthu Mahabeer Polliah , Lara Lewis , Farzana Osman , Precious Radebe , Jo-Ann S. Passmore , Doug Kwon , Jacques Ravel , Sinaye Ngcapu , Lenine Liebenberg , Laura Symul , Susan Holmes , Caroline M. Mitchell , Disebo Potloane

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引用次数: 0

Abstract

Background

Globally, approximately 30 % of women have bacterial vaginosis (BV). Antibiotic treatment is frequently followed by recurrence, likely due to lack of colonization with beneficial lactobacilli.

Methods

This is a Phase 1, randomized, placebo-controlled trial of vaginal live biotherapeutic products (LBP) after antibiotic treatment for BV to establish Lactobacillus colonization. The LBP are vaginal tablets containing 6 L. crispatus strains (LC106) or 15 L. crispatus strains (LC115), at 2 x 10⁹ colony forming units (CFU) per dose. Participants with BV in the United States and South Africa will receive seven days of oral metronidazole twice daily and will be randomized 1:1:1:1:1 to: seven days placebo; seven days LC106; three days LC106/four days placebo; seven days LC106 starting day 3 of the metronidazole course; or seven days LC115. Safety will be assessed by the number and percentage of ≥ Grade 2 related adverse events during or after product use. The primary outcome is LBP colonization defined as relative abundance ≥5 % of any LBP strain or ≥10 % of a combination of LBP strains by metagenomic sequencing any time in the 5 weeks after randomization. A generalized linear model will measure the association between treatment group and colonization, adjusting for site.

Conclusions

This study seeks to establish proof of concept for a multi-strain LBP to promote vaginal L. crispatus colonization in two geographically distinct populations.

Trial registration

South African National Clinical Trials Registry (SANCTR DOH-27-102023-8342; October 27, 2023) and ClinicalTrials.gov (NCT06135974; November 11, 2023).

Protocol version

2.0 dated October 03, 2023.

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细菌性阴道病抗生素治疗后多菌种crispr乳杆菌阴道活生物治疗产品的随机试验：研究方案（阴道活生物治疗随机试验）

在全球范围内，大约30%的女性患有细菌性阴道病（BV）。抗生素治疗后经常复发，可能是由于缺乏有益的乳酸菌定植。方法：这是一项随机、安慰剂对照的i期临床试验，研究阴道活生物治疗产品（LBP）在抗生素治疗细菌性阴道炎后建立乳杆菌定植。LBP是阴道片剂，含有6株葡萄球菌（LC106）或15株葡萄球菌（LC115），每剂量2 × 109菌落形成单位（CFU）。美国和南非的BV患者将接受为期7天的甲硝唑口服治疗，每日两次，并将按1:1:1:1:1随机分配至：7天安慰剂；7天LC106；3天LC106/ 4天安慰剂；7天LC106，甲硝唑疗程第3天开始；或7天LC115。安全性将通过产品使用期间或使用后≥2级相关不良事件的数量和百分比进行评估。主要终点是LBP定殖，定义为随机分组后5周内任何时间任何LBP菌株的相对丰度≥5%或LBP菌株组合的相对丰度≥10%。一个广义的线性模型将测量治疗组和定植之间的关系，调整地点。结论本研究旨在建立多菌株LBP在两个地理上不同的人群中促进阴道crispatus定植的概念证明。试验注册：南非国家临床试验注册中心（SANCTR DOH-27-102023-8342； 2023年10月27日）和ClinicalTrials.gov （NCT06135974； 2023年11月11日）。协议版本2.0，日期为2023年10月3日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Contemporary Clinical Trials Communications Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

2.70

自引率

6.70%

发文量

146

审稿时长

20 weeks

期刊介绍： Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.