Single Dose Antibiotic Treatment of Acute Watery Diarrhea, Rifaximin Versus Azithromycin, With Loperamide Adjunct

NCT05677282 | Recruiting Phase 4 FDA Drug

• 1 other identifier: IDCRP-115
• Study Type: interventional
• Target: 150
• Locations: 4 countries
• Sites: 4

Brief Summary

The purpose of this study is to compare a single dose of rifaximin with loperamide to the current standard approach of single dose azithromycin with loperamide for the treatment of acute watery traveler's diarrhea (TD). The study requires 1) taking a single dose antibiotic plus loperamide to treat TD, 2) providing blood and stool samples at different time points to evaluate infection and immune responses, 3) completing a daily symptom diary following treatment, 4) being seen by the study doctor to monitor illness and recovery, and 5) completing a brief electronic questionnaire at 3 months. Participants will be randomly assigned to one of the two treatment groups. The two groups are 1) rifaximin 550 mg as a single dose with loperamide 4 mg initially followed by 2 mg after each unformed stool or 2) azithromycin 500 mg as a single dose with loperamide 4 mg initially followed by 2 mg after each unformed stool. Both groups will take the antibiotic dose and 4 mg of loperamide.

Conditions

Diarrhoea;Acute; Diarrhea Travelers

Outcome Measures

Primary Outcomes (1)

• Therapeutic efficacy of single-dose rifaximin (550 mg) with loperamide in treating acute watery diarrhea compared to single-dose azithromycin (500 mg) with loperamide.

  Time to last unformed stool (TLUS), in hours, is calculated from the time of antibiotic dose to last unformed (diarrheal) stool (TLUS).

  Up to 1 week (up to 168 hours)

Secondary Outcomes (4)

• Proportion of participants no longer meeting TD illness criteria at 24 hours

  24 hours

• Proportion of participants no longer meeting TD illness criteria at 72 hours

  72 hours

• Proportion of participants with recurrence of TD illness after previous resolution of TD illness

  7 days

• Proportions of serious adverse events (SAE) at 21 days

  21 days

Study Arms (2)

Rifaximin with loperamide

EXPERIMENTAL

Drug: Rifaximin 550 MG; Drug: Loperamide

Azithromycin mg with loperamide

ACTIVE COMPARATOR

Drug: Azithromycin 500 MG; Drug: Loperamide

Interventions

Rifaximin 550 MG DRUG

Rifaximin 550 mg as a single dose administered orally.

Rifaximin with loperamide

Azithromycin 500 MG DRUG

Azithromycin 500 mg as a single dose administered orally.

Azithromycin mg with loperamide

Loperamide DRUG

4 mg loperamide administered orally with study antibiotic (rifaximin or azithromycin). Additional loperamide to use as needed, but not to exceed 16 mg/day for 2 days as per licensed use (one 2 mg capsule after each looses stool).

Azithromycin mg with loperamide; Rifaximin with loperamide

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Active duty military, 18-60 years old
• Presence of acute watery diarrhea (3 or more loose/liquid stools in 24 hours or 2 loose/liquid stools in 24 hours and associated symptoms such as nausea, vomiting, abdominal cramps or tenesmus) lasting \<96 hours in duration that impacts function in activities and/or performance of primary duties. Refer to recruitment decision tree below.
• Eligible for ambulatory management. (Note: Ambulatory management in this study means that the patient can be treated on an outpatient basis to include up to 23 hours of medical observation and IV therapies.)
• Able to comply with follow-up procedures.
• Will remain in country for at least 7 days or an assurance that follow-up can be arranged elsewhere.

You may not qualify if:

• Allergy to rifamycins, macrolides, or loperamide (not including mild gastrointestinal upset).
• Antibiotic therapy in the 72 hours prior to presentation (excluding malaria prophylaxis with mefloquine, malarone, chloroquine/proguanil, tafenoquine, or doxycycline).
• Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, warfarin, chloroquine and hydroxychloroquine).
• Current or history of liver disease or other serious health conditions based on review by study physician.
• Acute dysentery and/or febrile illness (temperature \> 100.4°F \[38.1°C\]).
• Presence of symptoms \>96 hours prior to initiating treatment.
• Use of \>4 mg loperamide or use of any amount of loperamide for greater than 24 hours prior to enrollment. Prior use of bismuth subsalicylate or other anti-diarrheal, non-antibiotic therapy in the 48 hours prior to enrollment.
• Positive pregnancy test at presentation (unknown effects with rifaximin). All female participants will be administered a urine pregnancy test prior to enrollment.
• Previously screened or randomized in this study.

Sponsors & Collaborators

• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• Infectious Diseases Clinical Research Program: collaborator
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (4)

Camp Lemonnier Djibouti

Djibouti, Djibouti

RECRUITING

JTF-Bravo, Soto Cano AB

Comayagua, Honduras

RECRUITING

British Army Training Site UK

Nanyuki, Kenya

RECRUITING

Fort Magsaysay & Camp Aguinaldo

Santa Rosa, Nueva Ecija, Philippines

ACTIVE NOT RECRUITING

MeSH Terms

Interventions

Rifaximin; Azithromycin; Loperamide

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Principal Investigator

CONTACT

240-855-6584; dtribble@idcrp.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, active-controlled, treatment trial of Travelers Diarrhea (TD) in an outpatient setting enrolling deployed United States (US) service members assigned to Joint Task Force (JTF)-Bravo, Soto Cano Air Base, Honduras and Camp Lemonnier, Djibouti (CLDJ) and United Kingdom (UK) military personnel to British Army Training Unit, Kenya (BATUK) who present for medical care with acute TD.

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: January 10, 2023
• Study Start: October 28, 2022
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Locations

HO (1); DJ (1); KE (1); PH (1)