Pharmacy and Poisons Board
Protocol No: ECCT/19/03/02 Date of Protocol: 14-11-2016
Study Title:

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 Travellers’ Diarrhoea (TD) Among Active Duty Deployed U.S. and British Military Personnel (PREVENT TD)
Study Objectives:

OBJECTIVES AND SPECIFIC AIMS

  1. Primary: To assess the efficacy of 550 mg rifaximin compared with placebo when taken twice daily (BID) or once-daily, by healthy subjects, to prevent TD.
  2. Secondary:
    1. Safety of rifaximin when compared to placebo when taken to prevent TD.
    2. As a secondary objective, the efficacy of rifaximin vs. placebo will be evaluated in terms of an expanded series of endpoints (See secondary efficacy endpoints).
  3. Exploratory:
    1. Quantify the occurrence of rifaximin resistance (primary and acquired) among enteropathogens and commensal flora.
    2. Evaluate effect of rifaximin prophylaxis on the enteric microbiome.
    3. Evaluate the risk and biomarkers of a functional gastrointestinal disorder among subjects with TD compared to those with no TD during surveillance period.
    4. Estimate the efficacy of chemoprophylaxis in preventing TD-associated long-term health outcomes, specifically functional gastrointestinal disorders (FGD) and Reactive Arthritis (ReA).
    5. Evaluate the onset of TD after cessation of prophylaxis among subjects who remain at Country of Deployment (COD) beyond maximal prophylaxis period.
    6. Obtain parameter estimates to inform a cost-effectiveness model of chemoprophylaxis strategy.
    7. Evaluate comparative efficacy of rifaximin in various geographic regions.

 

  1. Secondary Endpoints (Efficacy):
    1. Secondary efficacy endpoints over the period of prophylaxis will include the proportion of subjects in each treatment group:
      1. With TD
      2. With mild diarrhea
      3. With treated diarrhoea (TD and mild diarrhoea)
      4. With TD associated with isolation of a pathogen and pathogen type (invasive vs. enterotoxigenic Escherichia coli (ETEC) or other non-invasive pathogen-(only among subjects with appropriate samples to perform evaluation)
      5. Total diarrhoeal days
      6. Work days and performance loss due to diarrhoea, and
      7. Comparison of incidence of TD (TD event number and person-time risk)

 
Laymans Summary:

The purpose of this study is to develop proof on the ability of 2 rifaximin medicines used for the prevention of Travellers’ Diarrhoea (TD) for military personnel sent to outer stations for different operations. In addition the study will try to find out the effect of the study medications on intestinal system's composition and antimicrobial resistance, and obtain any new information to help come up with a cost-effective use of medications used in prevention of TD. Information from this study will be used to develop management guidelines for the prevention of TD among military personnel from the United States (US) and United Kingdom (UK).

 
Abstract of Study:

The purpose of this study is to develop evidence on the relative efficacy of 2 rifaximin chemoprophylaxis regimens for the prevention of Travellers’ Diarrhoea (TD) in a deployed setting. In addition the study will 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.