A Phase 4 interventional study of Rifaximin 550 MG and Azithromycin 500 MG in Diarrhoea;Acute and Diarrhea Travelers, sponsored by Henry M. Jackson Foundation for the Advancement of Military Medicine. Active, not recruiting at 4 sites in 4 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Henry M. Jackson Foundation for the Advancement of Military Medicine · Phase 4, Interventional, and Treatment
U.K. Ministry of Defence Research (MoD) · U.S. Naval Medical Research Unit - EURAFCENT (NAMRU-EURAFCENT) · U.S. Naval Medical Research Unit South (NAMRU-SOUTH) · Walter Reed Army Institute of Research - Armed Forces Research Institute of Medical Science (WRAIR-AFRIMS) · Walter Reed Army Institute of Research - Africa (WRAIR-Africa) · Navy Medical Research Command (NMRC)
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 or 2) azithromycin 500 mg as a single dose with loperamide. Both groups will take the antibiotic dose with 4 mg of loperamide. Participants are provided additional loperamide with instructions that they may take a 2 mg after continued diarrheal stools up to a maximum of 8 mg per day as needed.
877 studies on the registry are indexed under Diarrhea; 76 are open to participants now.
This study's enrollment of 128 is close to the median of 137 across 738 interventional studies indexed under Diarrhea.
Browse Diarrhea studies →Henry M. Jackson Foundation for the Advancement of Military Medicine is the lead sponsor of 86 studies on the registry; 18 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 2 (29%) have results posted.
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Drug: Rifaximin 550 MG · Drug: Loperamide
Drug: Azithromycin 500 MG · Drug: Loperamide
Rifaximin 550 mg as a single dose administered orally.
Azithromycin 500 mg as a single dose administered orally.
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).
Therapeutic Efficacy: Time to Last Unformed Stool (TLUS)
The primary efficacy endpoint is the time to last unformed stool (TLUS). TLUS is calculated from the time of antibiotic dose to last unformed stool meeting the pre-defined traveler's diarrhea definition.
Time frame: Up to 1 week (up to 168 hours)
Clinical Cure Rate
The clinical efficacy cure rate is the percentage of participants that met criteria for both diarrhea resolution and symptom resolution within the specified window, at 24, 48, and 72 hours following initial study treatment. To meet criteria for symptom resolution, there must be no traveler's diarrhea (TD) associated symptoms reported as moderate or greater and no impact on activities for last 24 hour period.
Time frame: 24, 48, and 72 hours
Return to Normal Activities
The percentage of participants that reported activities were not impacted at the end of the specified window, at 24, 48, and 72 hours following initial study treatment.
Time frame: 24, 48, and 72 hours
Number of Participants With Recurrence of Traveler's Diarrhea
Participants that experienced a recurrence of traveler's diarrhea after previously meeting criteria for clinical cure resolution.
Time frame: 7 days
Number of Participants Requiring Rescue Treatment
The number of participants whose illness worsened or continued to impact functional capacity at the 72-hour time point requiring their treatment code to be broken so appropriate rescue treatment could be prescribed.
Time frame: 3 days
Deployed United States (U.S.) and United Kingdom (U.K.) active duty military personnel ages 18-60 years that presented with acute watery diarrhea and were deemed suitable for ambulatory therapy were recruited at four locations between October 2022 and June 2025. U.S. military personnel were recruited at JTF-Bravo, Soto Cano Air Base, Honduras; Camp Lemonnier, Djibouti (CLDJ); and Exercise Balikatan 2025. U.K. military personnel were recruited at British Army Training Unit, Kenya (BATUK).
| Milestone | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) ITT | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) ITT |
|---|---|---|
| Started | 61 | 58 |
| Completed | 60 | 58 |
| Not completed | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
The primary efficacy endpoint is the time to last unformed stool (TLUS). TLUS is calculated from the time of antibiotic dose to last unformed stool meeting the pre-defined traveler's diarrhea definition.
| hours | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP |
|---|---|---|
| Therapeutic Efficacy: Time to Last Unformed Stool (TLUS) | 14 (0.4 to 24) | 19 (2 to 30) |
The clinical efficacy cure rate is the percentage of participants that met criteria for both diarrhea resolution and symptom resolution within the specified window, at 24, 48, and 72 hours following initial study treatment. To meet criteria for symptom resolution, there must be no traveler's diarrhea (TD) associated symptoms reported as moderate or greater and no impact on activities for last 24 hour period.
| percentage of participants | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP |
|---|---|---|
| 24 hours | 31.6 (19.9 to 45.2) | 22.4 (12.5 to 35.3) |
| 48 hours | 64.9 (51.1 to 77.1) | 56.9 (43.2 to 69.8) |
| 72 hours | 80.7 (68.1 to 90.0) | 79.3 (66.7 to 88.8) |
The percentage of participants that reported activities were not impacted at the end of the specified window, at 24, 48, and 72 hours following initial study treatment.
| percentage of participants | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP |
|---|---|---|
| 24 hours | 38.6 (26.0 to 52.4) | 29.3 (18.1 to 42.7) |
| 48 hours | 73.7 (60.3 to 84.4) | 62.1 (48.4 to 74.4) |
| 72 hours | 89.4 (78.4 to 96.0) | 79.3 (66.7 to 88.8) |
Participants that experienced a recurrence of traveler's diarrhea after previously meeting criteria for clinical cure resolution.
| Participants | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP |
|---|---|---|
| Number of Participants With Recurrence of Traveler's Diarrhea | 3 | 2 |
The number of participants whose illness worsened or continued to impact functional capacity at the 72-hour time point requiring their treatment code to be broken so appropriate rescue treatment could be prescribed.
| Participants | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP |
|---|---|---|
| Number of Participants Requiring Rescue Treatment | 1 | 0 |
Collected over From enrollment until end of in-person follow-up (21 days). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) ITT | 0/61 (0%) | 0/61 (0%) | 6/61 (9.8%) |
| Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) ITT | 0/58 (0%) | 0/58 (0%) | 6/58 (10.3%) |
| Event | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) ITT | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) ITT |
|---|---|---|
| Nausea (without vomiting) during 30-minute post administration observationGastrointestinal disorders | 2/61 | 6/58 |
| Nausea and vomiting during 30-minute post administration observationGastrointestinal disorders | 1/61 | 0/58 |
| Vasovagal SyncopeVascular disorders | 1/61 | 0/58 |
| Tonsillar AbscessInfections and infestations | 1/61 | 0/58 |
| Vaginal Yeast InfectionInfections and infestations | 1/61 | 0/58 |
Two participants that received study treatment did not meet criteria for documented evidence of diarrhea based on review of submitted stool specimen; this eligibility deviation was identified post-randomization and the participants were excluded from the PP cohort but followed for safety. One participant completed study visits but did not return a study diary was excluded from the PP cohort.
| Age, Continuous(years) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Median | 31 (26 to 37) | 30.5 (25 to 37) | 31 (25 to 37) |
| Sex: Female, Male(Participants) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Female | 9 | 8 | 17 |
| Male | 48 | 50 | 98 |
| Race/Ethnicity, Customized(Participants) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Race — White | 42 | 47 | 89 |
| Race — Black | 10 | 7 | 17 |
| Race — Asian | 1 | 2 | 3 |
| Race — Native Hawaiian/ Pacific Islander | 1 | 1 | 2 |
| Race — Multiple | 3 | 1 | 4 |
| Region of Enrollment(Participants) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Kenya | 18 | 16 | 34 |
| Djibouti | 15 | 18 | 33 |
| Honduras | 18 | 18 | 36 |
| Philippines | 6 | 6 | 12 |
| Duration of Illness Prior to Enrollment(days) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Median | 1 (1 to 2) | 1 (1 to 2) | 1 (1 to 2) |
| Diarrheal Stool Count in 24 hours Pre-Randomization(diarrheal stools) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Median | 8 (4 to 10) | 9 (6 to 12) | 8 (5 to 11) |
| Severe Symptoms the Day of Presentation and Randomization(Participants) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Diarrhea | 15 | 16 | 31 |
| Vomiting | 4 | 1 | 5 |
| Nausea | 3 | 2 | 5 |
| Fever (Subjective) | 1 | 0 | 1 |
| Abdominal Cramps | 5 | 7 | 12 |
| Malaise/Fatigue | 4 | 5 | 9 |
| Any Severe Symptoms | 18 | 22 | 40 |
| Impact of Illness on Activity Level the Day of Presentation and Randomization(Participants) | Single-dose Rifaximin (550 mg) Plus Loperamide (4 mg) PP | Single-dose Azithromycin (500 mg) Plus Loperamide (4 mg) PP | Total |
|---|---|---|---|
| Normal Activity Level | 0 | 0 | 0 |
| Decreased Activity ≤50% | 15 | 19 | 34 |
| Decreased Activity >50% | 39 | 35 | 74 |
| Completely Unable to Function | 3 | 4 | 7 |
PDFs hosted by the registry, ClinicalTrials.gov.
U.K. Ministry of Defence Research (MoD) · U.S. Naval Medical Research Unit - EURAFCENT (NAMRU-EURAFCENT) · U.S. Naval Medical Research Unit South (NAMRU-SOUTH) · Walter Reed Army Institute of Research - Armed Forces Research Institute of Medical Science (WRAIR-AFRIMS) · Walter Reed Army Institute of Research - Africa (WRAIR-Africa) · Navy Medical Research Command (NMRC)
U.K. Ministry of Defence Research (MoD) · U.S. Naval Medical Research Unit - EURAFCENT (NAMRU-EURAFCENT) · U.S. Naval Medical Research Unit South (NAMRU-SOUTH) · Walter Reed Army Institute of Research - Armed Forces Research Institute of Medical Science (WRAIR-AFRIMS) · Walter Reed Army Institute of Research - Africa (WRAIR-Africa) · Navy Medical Research Command (NMRC)
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Studies of the drug tested here: Rifaximin
Henry M. Jackson Foundation for the Advancement of Military Medicine