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

Official title

A Randomized Controlled Trial Evaluating Single-dose Rifaximin Versus Azithromycin With Loperamide Adjunct for Treatment of Acute Watery Diarrhea

Overview

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.

Interventions

• Drug Rifaximin 550 MG
  Rifaximin 550 mg as a single dose administered orally.
• Drug Azithromycin 500 MG
  Azithromycin 500 mg as a single dose administered orally.
• Drug Loperamide
  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).

Primary outcome measures

• 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 frame: Up to 1 week (up to 168 hours)]

Secondary outcome measures (4)

• Proportion of participants no longer meeting TD illness criteria at 24 hours [Time frame: 24 hours]
• Proportion of participants no longer meeting TD illness criteria at 72 hours [Time frame: 72 hours]
• Proportion of participants with recurrence of TD illness after previous resolution of TD illness [Time frame: 7 days]
• Proportions of serious adverse events (SAE) at 21 days [Time frame: 21 days]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Djibouti · 1 center

• Camp Lemonnier Djibouti — Djibouti

Honduras · 1 center

• JTF-Bravo, Soto Cano AB — Comayagua

Kenya · 1 center

• British Army Training Site UK — Nanyuki

Philippines · 1 center

• Fort Magsaysay & Camp Aguinaldo — Santa Rosa

Identifiers

NCT: NCT05677282 · IDCRP-115

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗