Diarrhoea;AcutePhase 4TrEAT_TD2NCT05677282
Single Dose Antibiotic Treatment of Acute Watery Diarrhea, Rifaximin Versus Azithromycin, With Loperamide Adjunct
A Phase 4 study testing Rifaximin 550 MG, Azithromycin 500 MG and Loperamide in people with Diarrhoea;Acute and Diarrhea Travelers, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 4 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diarrhoea;Acute, Diarrhea Travelers
- What is being tested?
- Rifaximin 550 MG, Azithromycin 500 MG and Loperamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 28 Oct 2022to Dec 2025
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 4 countries
Djibouti1 site, 1 recruiting
- Recruiting
Camp Lemonnier Djibouti
Djibouti
Principal Investigator, 233 54 011 5776, elizabeth.s.cooper5.mil@health.mil
Honduras1 site, 1 recruiting
- Recruiting
JTF-Bravo, Soto Cano AB
Comayagua
Principal Investigator, 51 996 830 701, danielle.l.pannebaker.mil@health.mil
Kenya1 site, 1 recruiting
- Recruiting
British Army Training Site UK
Nanyuki
Principal Investigator, 07713 630916, richard.makins@nhs.net
Philippines1 site
- Active, not recruiting
Fort Magsaysay & Camp Aguinaldo
Santa Rosa, Nueva Ecija
About this study
Official title: A Randomized Controlled Trial Evaluating Single-dose Rifaximin Versus Azithromycin With Loperamide Adjunct for Treatment of Acute Watery Diarrhea
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
- Being tested
- Rifaximin 550 MG, Azithromycin 500 MG, Loperamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifaximin 550 MGDrug
Rifaximin 550 mg as a single dose administered orally.
Azithromycin 500 MGDrug
Azithromycin 500 mg as a single dose administered orally.
LoperamideDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin with loperamide | Experimental | Not described Receives: Drug: Rifaximin 550 MG; Drug: Loperamide |
| Azithromycin mg with loperamide | Active comparator | Not described Receives: Drug: Azithromycin 500 MG; Drug: Loperamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 1 week (up to 168 hours)
Secondary outcomes (4)
Proportion of participants no longer meeting TD illness criteria at 24 hours
The clinical efficacy cure rate at 24h is the proportion of participants at the 24h follow up after the initial treatment who met the end point of not meeting TD illness.
Measured: 24 hours
Proportion of participants no longer meeting TD illness criteria at 72 hours
For the clinical efficacy cure rate at 72h is the proportions of participants who met the end point
- no report of unformed/diarrheal/loose/liquid stool (LLS) that meet TD illness >24h after initial treatment and
- TD-associated symptoms present at 24h were not reported as moderate or greater
Measured: 72 hours
Proportion of participants with recurrence of TD illness after previous resolution of TD illness
TD recurrence at 7d follow up if participants meet TD illness and had the previous cure resolution at 24h or 72h
Measured: 7 days
Proportions of serious adverse events (SAE) at 21 days
Proportions of serious adverse events (SAE)
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2023
- Study start28 Oct 2022
- Primary completionSep 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diarrhoea;AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05677282
- Sponsor's protocol ID
- IDCRP-115
- Acronym
- TrEAT_TD2
- Status last verified
- May 2025
- First submitted
- 4 Nov 2022
- Last updated
- 31 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Evaluating Single-dose Rifaximin Versus Azithromycin With Loperamide Adjunct for Treatment of Acute Watery Diarrhea
- ClinicalTrials.gov ID
- NCT05677282
- Acronym / sponsor ID
- TrEAT_TD2 / IDCRP-115
- Conditions
- Diarrhoea;Acute, Diarrhea Travelers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military MedicineUniversity, hospital or other
- Collaborators
- Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences
- Study start
- 28 Oct 2022 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 10 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Rifaximin with loperamide | Experimental | Drug: Rifaximin 550 MG, Drug: Loperamide |
| Azithromycin mg with loperamide | Active comparator | Drug: Azithromycin 500 MG, Drug: Loperamide |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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]).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rifaximin 550 MGRifaximin 550 mg as a single dose administered orally. | Drug | Rifaximin with loperamide |
| Azithromycin 500 MGAzithromycin 500 mg as a single dose administered orally. | Drug | Azithromycin mg with loperamide |
| Loperamide4 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). | Drug | Azithromycin mg with loperamide, Rifaximin with loperamide |
Primary outcome
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)
Time to last unformed stool (TLUS), in hours, is calculated from the time of antibiotic dose to last unformed (diarrheal) stool (TLUS).
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifaximin 550 MG, Azithromycin 500 MG and Loperamide in people with Diarrhoea;Acute and Diarrhea Travelers, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Djibouti, Honduras, Kenya, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Principal Investigator (240-855-6584, dtribble@idcrp.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.