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

Uniformed Services University (USU)

Status: Terminated

Conditions: Acute Watery Diarrhea; Dysentery/Febrile Diarrhea

Treatments: Drug: Single dose azithromycin 500 mg; Drug: Single dose levofloxacin 500 mg; Drug: Single dose azithromycin 1000 mg plus placebo; Drug: Single dose azithromycin 1000 mg plus loperamide; Drug: Single dose rifaximin 1650 mg

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01618591

IDCRP-065

Details and patient eligibility

About

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.

Full 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.

Enrollment: 384 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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384 participants in 2 patient groups

Acute Watery Diarrhea

Experimental group

Treatment:

Drug: Single dose azithromycin 500 mg

Drug: Single dose rifaximin 1650 mg

Drug: Single dose levofloxacin 500 mg

Acute Dysentery/Febrile

Experimental group

Treatment:

Drug: Single dose azithromycin 1000 mg plus loperamide

Drug: Single dose azithromycin 1000 mg plus placebo