Acute Watery DiarrheaTrEAT TDNCT01618591
Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea
A study testing Single dose rifaximin 1650 mg, Single dose azithromycin 500 mg and Single dose levofloxacin 500 mg in people with Acute Watery Diarrhea and Dysentery/Febrile Diarrhea, run by Uniformed Services University of the Health Sciences at 5 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Watery Diarrhea, Dysentery/Febrile Diarrhea
- What is being tested?
- Single dose rifaximin 1650 mg, Single dose azithromycin 500 mg and Single dose levofloxacin 500 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 384 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Sep 2012to Mar 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active duty military or military beneficiary, 18 years-old or older.
- 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.
- Eligible for ambulatory management.
- Able to comply with follow-up procedures.
- Will remain in country for at least 7 days
Who cannot join
- Allergy to rifamycins, quinolones, 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, or doxycycline).
- Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, and warfarin).
- History of seizures (relative contraindication to quinolones)
- Positive pregnancy test at presentation (contraindicated with fluoroquinolone therapy). All female subjects will be administered a urine pregnancy test prior to enrollment.
- 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.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Djibouti1 site
U.S. Naval Expeditionary Base
Camp Lemonnier
About this study
Official title: A Randomized, Double-Blind, Clinical Trial Evaluating Three Single Dose Regimens With Loperamide for Treatment of Ambulatory Watery Travelers' Diarrhea, and Azithromycin With and Without Loperamide for Treatment of Ambulatory Dysentery/Febrile Diarrhea
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.
Read the detailed 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.
- Conditions
- Acute Watery Diarrhea, Dysentery/Febrile Diarrhea
- Being tested
- Single dose rifaximin 1650 mg, Single dose azithromycin 500 mg, Single dose levofloxacin 500 mg, Single dose azithromycin 1000 mg plus loperamide, Single dose azithromycin 1000 mg plus placebo
- Keywords
- diarrhea, travelers' diarrhea, watery diarrhea, enteric illness, dysentery, gastrointestinal
- Medical subject headings
- Dysentery, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single dose rifaximin 1650 mgDrug
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
Single dose azithromycin 500 mgDrug
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
Single dose levofloxacin 500 mgDrug
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
Single dose azithromycin 1000 mg plus loperamideDrug
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
Single dose azithromycin 1000 mg plus placeboDrug
Azithromycin 1000 mg as a single dose and placebo in lieu of loperamide
| Study group | Role | What they receive |
|---|---|---|
| Acute Watery Diarrhea | Experimental | Not described Receives: Drug: Single dose rifaximin 1650 mg; Drug: Single dose azithromycin 500 mg; Drug: Single dose levofloxacin 500 mg |
| Acute Dysentery/Febrile | Experimental | Not described Receives: Drug: Single dose azithromycin 1000 mg plus loperamide; Drug: Single dose azithromycin 1000 mg plus placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Cure - Acute Watery Diarrhea group
- No grade 3-5 stools beyond 24 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period). All diarrhea associated symptoms present must be no greater than mild in severity and have no impact on activity.
- AND, no treatment failure events to include the following:
- Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure
- Worsening of, or failure to improve, clinical symptoms after 24 hours of therapy
- Illness continuing after 72 hours
Measured: 24 hours
Clinical Cure - Acute Dysentery/Febrile Diarrhea group
- No grade 3-5 stools beyond 48 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period) and resolution of acute dysentery/febrile diarrhea-associated signs/symptoms to include fever and gross blood in stool, as well as report of no impact on activity
- AND, no treatment failure events to include the following:
- Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure
- Worsening of, or failure to improve after 24 hours of therapy
- Illness continuing after 72 hours
Measured: 48 hours
Secondary outcomes (1)
Time to Last Unformed Stool
Calculated as the time from taking the first dose of study medication until passage of the last unformed stool that meets diarrhea definition (grade 3-5 stool associated with 2 other loose stools in 24 hours or 1 other loose stool and associated symptoms in that same 24 hour block) after which subjects are declared well. Where, last unformed stool = last grade 3-5 stool occurring in a 24-hr period meeting the diarrhea definition.
Measured: 24, 48, 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2012 (estimated)
- Study startSep 2012
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: AWD arm was completed. ADF diarrhea arm was unable to fill completely and there are no funds remaining to continue recruiting/enrolling.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Watery DiarrheaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 384 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uniformed Services University of the Health Sciences
- Sponsor type
- US federal agency
- Collaborators
- Navy Bureau of Medicine and Surgery, Ministry of Defence, United Kingdom, Naval Medical Research Center, Naval Medical Research Unit- 3, United States Army Medical Unit - Kenya, United States Naval Medical Center, Portsmouth, Naval Medical Research Unit- 6
- Responsible party
- Principal investigator, Mark Riddle, CDR, MC, USN, Naval Medical Research Center
- Investigators
- Mark Riddle, MD, DrPH, Principal investigator, Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01618591
- Sponsor's protocol ID
- IDCRP-065
- Acronym
- TrEAT TD
- Status last verified
- Nov 2016
- First submitted
- 1 Jun 2012
- Last updated
- 28 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Johnson RC, Van Nostrand JD, Tisdale M, Swierczewski B, Simons MP, Connor P, Fraser J, Melton-Celsa AR, Tribble DR, Riddle MS. Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers' Diarrhea. Open Forum Infect Dis. 2021 May 28;8(6):ofab271. doi: 10.1093/ofid/ofab271. eCollection 2021 Jun.
PubMed 34189178Riddle MS, Connor P, Fraser J, Porter CK, Swierczewski B, Hutley EJ, Danboise B, Simons MP, Hulseberg C, Lalani T, Gutierrez RL, Tribble DR; TrEAT TD Study Team. Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide. Clin Infect Dis. 2017 Nov 29;65(12):2008-2017. doi: 10.1093/cid/cix693.
PubMed 29029033
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Clinical Trial Evaluating Three Single Dose Regimens With Loperamide for Treatment of Ambulatory Watery Travelers' Diarrhea, and Azithromycin With and Without Loperamide for Treatment of Ambulatory Dysentery/Febrile Diarrhea
- ClinicalTrials.gov ID
- NCT01618591
- Acronym / sponsor ID
- TrEAT TD / IDCRP-065
- Conditions
- Acute Watery Diarrhea, Dysentery/Febrile Diarrhea
- Keywords
- diarrhea, travelers' diarrhea, watery diarrhea, enteric illness, dysentery, gastrointestinal
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: AWD arm was completed. ADF diarrhea arm was unable to fill completely and there are no funds remaining to continue recruiting/enrolling.
- Enrolment
- 384 participants (actual)
- Lead sponsor
- Uniformed Services University of the Health SciencesUS federal agency
- Collaborators
- Navy Bureau of Medicine and Surgery, Ministry of Defence, United Kingdom, Naval Medical Research Center, Naval Medical Research Unit- 3, United States Army Medical Unit - Kenya, United States Naval Medical Center, Portsmouth, Naval Medical Research Unit- 6
- Study start
- Sep 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 13 Jun 2012 (estimated)
- 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 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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute Watery Diarrhea | Experimental | Drug: Single dose rifaximin 1650 mg, Drug: Single dose azithromycin 500 mg, Drug: Single dose levofloxacin 500 mg |
| Acute Dysentery/Febrile | Experimental | Drug: Single dose azithromycin 1000 mg plus loperamide, Drug: Single dose azithromycin 1000 mg plus placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Active duty military or military beneficiary, 18 years-old or older.
- 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.
- Eligible for ambulatory management.
- Able to comply with follow-up procedures.
- Will remain in country for at least 7 days
Key exclusion criteria (7 listed)
- Allergy to rifamycins, quinolones, 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, or doxycycline).
- Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, and warfarin).
- History of seizures (relative contraindication to quinolones)
- Positive pregnancy test at presentation (contraindicated with fluoroquinolone therapy). All female subjects will be administered a urine pregnancy test prior to enrollment.
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 |
|---|---|---|
| Single dose rifaximin 1650 mgRifaximin 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 | Drug | Acute Watery Diarrhea |
| Single dose azithromycin 500 mgAzithromycin 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 | Drug | Acute Watery Diarrhea |
| Single dose levofloxacin 500 mgLevofloxacin 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 | Drug | Acute Watery Diarrhea |
| Single dose azithromycin 1000 mg plus loperamideAzithromycin 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 | Drug | Acute Dysentery/Febrile |
| Single dose azithromycin 1000 mg plus placeboAzithromycin 1000 mg as a single dose and placebo in lieu of loperamide | Drug | Acute Dysentery/Febrile |
Primary outcome
Clinical Cure - Acute Watery Diarrhea group
Time frame: 24 hours
* No grade 3-5 stools beyond 24 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period). All diarrhea associated symptoms present must be no greater than mild in severity and have no impact on activity. * AND, no treatment failure events to include the following: * Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure * Worsening of, or failure to improve, clinical symptoms after 24 hours of therapy * Illness continuing after 72 hours
Clinical Cure - Acute Dysentery/Febrile Diarrhea group
Time frame: 48 hours
* No grade 3-5 stools beyond 48 hours after initiation of therapy meeting diarrhea definition (≥3 loose or liquid stools in 24 hour period) and resolution of acute dysentery/febrile diarrhea-associated signs/symptoms to include fever and gross blood in stool, as well as report of no impact on activity * AND, no treatment failure events to include the following: * Recurrence of diarrheal illness meeting case definition of TD occurring within 72 hours after clinical cure * Worsening of, or failure to improve after 24 hours of therapy * Illness continuing after 72 hours
1 secondary outcome
Time to Last Unformed Stool
Time frame: 24, 48, 72 hours
Results and safety
The study was stopped early (reason given: AWD arm was completed. ADF diarrhea arm was unable to fill completely and there are no funds remaining to continue recruiting/enrolling.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Derived from this study: PubMed 34189178Johnson RC, Van Nostrand JD, Tisdale M, Swierczewski B, Simons MP, Connor P, Fraser J, Melton-Celsa AR, Tribble DR, Riddle MS. Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers' Diarrhea. Open Forum Infect Dis. 2021 May 28;8(6):ofab271. doi: 10.1093/ofid/ofab271. eCollection 2021 Jun.
- Derived from this study: PubMed 29029033Riddle MS, Connor P, Fraser J, Porter CK, Swierczewski B, Hutley EJ, Danboise B, Simons MP, Hulseberg C, Lalani T, Gutierrez RL, Tribble DR; TrEAT TD Study Team. Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide. Clin Infect Dis. 2017 Nov 29;65(12):2008-2017. doi: 10.1093/cid/cix693.
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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. This study is not recruiting at the moment.
Mark Riddle, MD, DrPH principal investigator
Naval Medical Research Center
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single dose rifaximin 1650 mg, Single dose azithromycin 500 mg and Single dose levofloxacin 500 mg in people with Acute Watery Diarrhea and Dysentery/Febrile Diarrhea, run by Uniformed Services University of the Health Sciences at 5 sites in 5 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 7 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: stopped early, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Afghanistan, Djibouti, Honduras, Kenya, Thailand. 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.
Are results available for this study?
The study was stopped early (reason given: AWD arm was completed. ADF diarrhea arm was unable to fill completely and there are no funds remaining to continue recruiting/enrolling.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Cure - Acute Watery Diarrhea group (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01618591, which also lists 2 linked publications.
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 28 Nov 2016.