Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea

NCT01618591 | Terminated DMC

• 1 other identifier: IDCRP-065
• Study Type: interventional
• Target: 384
• Locations: 5 countries
• Sites: 5

Brief 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. 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.

Conditions

Acute Watery Diarrhea; Dysentery/Febrile Diarrhea

Keywords

diarrhea; travelers' diarrhea; watery diarrhea; enteric illness; dysentery; gastrointestinal

Outcome Measures

Primary Outcomes (2)

• 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

  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

  48 hours

Secondary Outcomes (1)

• Time to Last Unformed Stool

  24, 48, 72 hours

Study Arms (2)

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

Interventions

Single dose rifaximin 1650 mg DRUG

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

Acute Watery Diarrhea

Single dose azithromycin 500 mg DRUG

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

Acute Watery Diarrhea

Single dose levofloxacin 500 mg DRUG

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

Acute Watery Diarrhea

Single dose azithromycin 1000 mg plus loperamide DRUG

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

Acute Dysentery/Febrile

Single dose azithromycin 1000 mg plus placebo DRUG

Azithromycin 1000 mg as a single dose and placebo in lieu of loperamide

Acute Dysentery/Febrile

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uniformed Services University of the Health Sciences: lead
• Navy Bureau of Medicine and Surgery: collaborator
• Ministry of Defence, United Kingdom: collaborator
• Naval Medical Research Center: collaborator
• Naval Medical Research Unit- 3: collaborator
• United States Army Medical Unit - Kenya: collaborator
• United States Naval Medical Center, Portsmouth: collaborator
• Naval Medical Research Unit- 6: collaborator

Study Sites (5)

UK Role 3 Joint Force Hospital

Camp Bastion Air Base, Afghanistan

Location

U.S. Naval Expeditionary Base

Camp Lemonnier, Djibouti

Location

Joint Task Force - Bravo

Soto Cano Air Base, Honduras

Location

British Army Training Unit Kenya

Nanyuki, Kenya

Location

Armed Forces Research Institute of Medical Sciences

Bangkok, Thailand

Location

Related Publications (2)

• 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.

  PMID: 34189178 DERIVED

• Riddle 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.

  PMID: 29029033 DERIVED

MeSH Terms

Conditions

Dysentery; Diarrhea

Interventions

Rifaximin; Azithromycin; Levofloxacin; Loperamide

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark Riddle, MD, DrPH

  Naval Medical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Enteric Diseases Department

Study Record Dates

• First Submitted: June 1, 2012
• First Posted: June 13, 2012
• Study Start: September 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: November 28, 2016

Record last verified: 2016-11

Locations

KE (1); TH (1); DJ (1); HO (1); AF (1)