A Randomized, Placebo-Controlled, Double-Blind, Clinical Trial Evaluating Two Dose Regimens of Rifaximin (550 mg Daily or 550 mg Twice Daily) for Chemoprophylaxis Against Travelers' Diarrhea (TD) Among Active Duty Deployed U.S. and British Military Personnel
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 449
- 试验地点
- 6
- 主要终点
- Efficacy - Risk of travelers diarrhea during chemoprophylaxis as measured by self-report via use of a memory aid
研究概览
简要总结
The purpose of this study is to develop evidence on the relative efficacy of 2 rifaximin chemoprophylaxis regimens for the prevention of Travelers' Diarrhea (TD) in a deployed setting. An additional purpose is to explore the effect of chemoprophylaxis on microbial flora and antimicrobial resistance, and obtain parameter estimates to inform a cost-effectiveness model of chemoprophylaxis in prevention of TD. Information from this study will be used to develop management guidelines for the prevention of TD among deployed (United States (US) and United Kingdom (UK) military personnel.
The study will be a multi-site, randomized, placebo-controlled, double-blind, clinical trial among deployed military personnel. The study will test 2 TD chemoprophylaxis regimens (once daily versus twice daily) of the same antibiotic, rifaximin, compared to a placebo.
For the proposed chemoprophylaxis study described herein, cohorts of military personnel (US and UK) deploying/traveling overseas will be recruited prior to travel to participate and will undergo enrollment procedures as outlined in study appendices. Subjects who are eligible and agree to participate will be randomized to receive one of 3 regimens: (1) rifaximin 550 mg daily; (2) rifaximin 550 mg twice a day; or (3) placebo, to be taken while deployed. Chemoprophylaxis will be maintained for duration of travel or a predetermined period of up to 6 weeks and at least 2 weeks, which may include a period of up to 5 days of use after return to COO for deployments less than 6 weeks in duration. Clinical and laboratory data will be obtained before, during if available and after deployment/chemoprophylaxis.
详细描述
The primary efficacy outcome will be assessed by review of the symptom memory aid (TravMil diary). Subjects will follow a symptom memory aid from the onset of a disease episode and record relevant symptomatology (date/time and number of diarrheal episodes, associated symptoms such as fever, vomiting, nausea, bloody stools and cramps, severity of symptoms, functional activity). Use of antibiotics and/or Imodium (loperamide) for each episode will also be recorded). An additional memory aid to capture occurrence of solicited adverse events, use of new prescription medications, as well as adherence to study medication regimen will be utilized by subjects during deployment and returned (or re-created with study personnel if lost or incomplete) at follow-up Memory aid data will be actively sought from all subjects via required in-person follow-up.
Secondary efficacy outcomes will also largely be derived from the self-report of subjects via use of the memory aid data. Secondary safety evaluation will be performed at the end of study visit based on history obtained from the subject regarding medical treatment requiring events while deployed.
Individuals will be enrolled prior to travel/deployment. At the time of enrollment they will undergo eligibility criteria review, informed consent process, baseline assessment (demographics, medical history, others), sample collection (blood and stool), and blinded randomization into a study arm.
Episodes of diarrhea are expected to occur while on study drug. Subjects will be instructed and expected to seek care for these episodes from medical assets available to them at COD.
Subjects will be instructed to discontinue study drug if they develop diarrhea and are given antibiotic therapy. It is not expected that study drug will impact the choice or effectiveness of antibiotics used to treat travelers' diarrhea. Some subjects will be eligible to restart (only once restart) study drug once they are cured of a travelers' diarrhea episode. See US and UK addenda for details.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •An Institutional Review Board (IRB) / Ethics Committee (EC)-approved informed consent form is signed and dated.
- •Subject is at least 18 years of age
- •Subject's duration of prophylaxis will be least 2 weeks.
- •Subject is capable of and willing to comply with all study procedures and available for the end of study visits and sample collection at COO (within 6 months from start of prophylaxis).
- •Women: Non-nursing and negative urine/serum pregnancy test with understanding (through informed consent process) to avoid pregnancy while on study drug. Sole reliance on oral contraceptives (OCPs) for birth control will not be recommended (see section 6.3.2.1.) Should an individual have a documented surgical sterilization in her medical record, a pregnancy test will not be required. If a volunteer becomes pregnant during the study, the principal investigator will notify the study research monitor and the IRBs. The pregnancy outcome will be followed per IRB and other regulatory requirements for US and UK personnel.
- •(For US Personnel Only). Have consented to participate in TravMil protocol.
排除标准
- •Subject received any systemic or gastrointestinal antibiotic in the 7 days prior to enrollment (except anti-malarial prophylaxis agents).
- •Subject has hypersensitivity or allergy to rifaximin or rifampicin.
- •Subject has acute diarrhea within 7 days prior to enrollment
- •Subject has a concomitant disease or condition that could interfere with, or for which treatment could interfere with, the conduct of the study, or could in the opinion of the investigator increase the risk of AEs during the subject's participation in the study
- •Subject is currently taking or plans to take during deployment at least one of the following medications: theophylline or warfarin (Coumadin).
研究组 & 干预措施
Rifaximin 550 mg once/day
rifaximin, 550 mg, once daily, by mouth
干预措施: Rifaximin (Drug)
Rifaximin 550 mg twice/day
rifaximin, 550 mg, twice daily, by mouth
干预措施: Rifaximin (Drug)
Rifaximin 550 mg twice/day
rifaximin, 550 mg, twice daily, by mouth
干预措施: Placebo (Drug)
Placebo
Placebo pills, twice daily, by mouth
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy - Risk of travelers diarrhea during chemoprophylaxis as measured by self-report via use of a memory aid
时间窗: 24hr
次要结局
- Solicited adverse events as collected from the subject and using a memory aid(For the duration of prophylaxis which will be on average 3-4 weeks or a maximum of 6 weeks.)
- Efficacy as determined by use of a symptom memory aid.(For a duration of prophylaxis which will be on average 3-4 weeks or a maximum of 6 weeks)