Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea (TrEAT TD)

November 24, 2016 updated by: Mark Riddle, CDR, MC, USN, Uniformed Services University of the Health Sciences

A Randomized, Double-Blind, Clinical Trial Evaluating Three Single Dose Regimens With Loperamide for Treatment of Ambulatory Watery Travelers' Diarrhea, and Azithromycin With and Without Loperamide for Treatment of Ambulatory Dysentery/Febrile Diarrhea

The purpose of the trial is to develop the evidence on relative efficacy of 3 available single-dose loperamide adjuncted regimens for watery diarrhea and a single-dose regimen, with and without loperamide, for dysentery/febrile diarrhea required for informing decisions among these regimens. Information from this study will be used to develop management guidelines for the diagnosis and management of travelers' diarrhea (TD) among deployed United States and United Kingdom military personnel.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The study will be a multi-site, randomized, double-blind, controlled clinical trial among ambulatory deployed personnel. Patients presenting for care will be clinically assessed and a determination made as to whether they have acute watery diarrhea (AWD) or acute dysentery/febrile diarrhea (ADF). For the AWD arm, patients will be randomized to receive 1 of 3 regimens: (1) rifaximin 1650 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days (120 subjects); (2) azithromycin 500 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days (120 subjects); or (3) levofloxacin 500 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days (120 subjects).

For the ADF arm, patients will be randomized to receive 1 of 2 regimens: (1) azithromycin 1000 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days (75 subjects); or (2) azithromycin 1000 mg as a single dose without loperamide (75 subjects).

Study Procedures (Brief): Baseline exam as well as blood and stool samples will be collected at initial clinic visit. Clinical assessments will be performed at 24 hours, 72 hours, and 7 days. In addition, microbiological cure will be evaluated at 7-d post initiation of treatment. Subjects will have blood drawn to assess for serological conversion to common enteric pathogens, and stool collected at 7- and 21-d . Subjects may also opt in for long-term follow-up at time of enrollment, which will assess for development of post-infectious functional bowel disorders. All subjects will complete a baseline assessment at 7-d visit, and those who opt for the additional follow-up will complete a series of web-based surveys at 3-, 6-, 9-, and 12-m post enrollment.

Study Type

Interventional

Enrollment (Actual)

384

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Afghanistan
      • Camp Bastion, Afghanistan
        • UK Role 3 Joint Force Hospital
  • Djibouti
      • Camp Lemonnier, Djibouti
        • U.S. Naval Expeditionary Base
  • Honduras
      • Soto Cano Air Base, Honduras
        • Joint Task Force - Bravo
  • Kenya
      • Nanyuki, Kenya
        • British Army Training Unit Kenya
  • Thailand
      • Bangkok, Thailand
        • Armed Forces Research Institute of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Active duty military or military beneficiary, 18 years-old or older.
  2. Presence of acute diarrhea (3 or more stools in 24 hours or 2 or more stools in 24 hours and associated symptoms such as nausea, vomiting, abdominal cramps or tenesmus) and <96 hours duration.
  3. Eligible for ambulatory management.
  4. Able to comply with follow-up procedures.
  5. Will remain in country for at least 7 days

Exclusion Criteria:

  1. Allergy to rifamycins, quinolones, macrolides, or loperamide (not including mild gastrointestinal upset).
  2. Antibiotic therapy in the 72 hours prior to presentation (excluding malaria prophylaxis with mefloquine, malarone, chloroquine/proguanil, or doxycycline).
  3. Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, and warfarin).
  4. History of seizures (relative contraindication to quinolones)
  5. Positive pregnancy test at presentation (contraindicated with fluoroquinolone therapy). All female subjects will be administered a urine pregnancy test prior to enrollment.
  6. Presence of symptoms >96 hours prior to initiating treatment.
  7. Use of >4 mg loperamide or use of any amount of loperamide for greater than 24 hours prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acute Watery Diarrhea
Drug: Single dose rifaximin 1650 mg
Rifaximin 1650 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days
Drug: Single dose azithromycin 500 mg
Azithromycin 500 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days
Drug: Single dose levofloxacin 500 mg
Levofloxacin 500 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days
Experimental: Acute Dysentery/Febrile
Drug: Single dose azithromycin 1000 mg plus loperamide
Azithromycin 1000 mg as a single dose plus loperamide 4 mg initially followed by 2 mg after each unformed stool, not to exceed 16 mg/day for 2 days
Drug: Single dose azithromycin 1000 mg plus placebo
Azithromycin 1000 mg as a single dose and placebo in lieu of loperamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Cure - Acute Watery Diarrhea group
Time Frame: 24 hours
  • No grade 3-5 stools beyond 24 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period). All diarrhea associated symptoms present must be no greater than mild in severity and have no impact on activity.

  • AND, no treatment failure events to include the following:

    • Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure
    • Worsening of, or failure to improve, clinical symptoms after 24 hours of therapy
    • Illness continuing after 72 hours
24 hours
Clinical Cure - Acute Dysentery/Febrile Diarrhea group
Time Frame: 48 hours
  • No grade 3-5 stools beyond 48 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period) and resolution of acute dysentery/febrile diarrhea-associated signs/symptoms to include fever and gross blood in stool, as well as report of no impact on activity

  • AND, no treatment failure events to include the following:

    • Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure
    • Worsening of, or failure to improve after 24 hours of therapy
    • Illness continuing after 72 hours
48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Last Unformed Stool
Time Frame: 24, 48, 72 hours
Calculated as the time from taking the first dose of study medication until passage of the last unformed stool that meets diarrhea definition (grade 3-5 stool associated with 2 other loose stools in 24 hours or 1 other loose stool and associated symptoms in that same 24 hour block) after which subjects are declared well. Where, last unformed stool = last grade 3-5 stool occurring in a 24-hr period meeting the diarrhea definition.
24, 48, 72 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Uniformed Services University of the Health Sciences

Collaborators

Naval Medical Research Center
Navy Bureau of Medicine and Surgery
Ministry of Defence, United Kingdom
Naval Medical Research Unit- 3
United States Army Medical Unit - Kenya
United States Naval Medical Center, Portsmouth
Naval Medical Research Unit- 6

Investigators

  • Principal Investigator: Mark Riddle, MD, DrPH, Naval Medical Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

June 1, 2012

First Submitted That Met QC Criteria

June 12, 2012

First Posted (Estimate)

June 13, 2012

Study Record Updates

Last Update Posted (Estimate)

November 28, 2016

Last Update Submitted That Met QC Criteria

November 24, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDCRP-065

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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