Clinical trial NCT01618591: Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Watery Diarrhea
Dysentery/Febrile Diarrhea
Keywords: diarrhea
travelers' diarrhea
watery diarrhea
enteric illness
dysentery
gastrointestinal
Lead sponsor: Uniformed Services University of the Health Sciences
Sponsor class: FED
Collaborators: name: Navy Bureau of Medicine and Surgery
name: Ministry of Defence, United Kingdom
name: Naval Medical Research Center
name: Naval Medical Research Unit- 3
name: United States Army Medical Unit - Kenya
name: United States Naval Medical Center, Portsmouth
name: Naval Medical Research Unit- 6
First posted: 2012-06-13
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Active duty military or military beneficiary, 18 years-old or older.
2. 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.
3. Eligible for ambulatory management.
4. Able to comply with follow-up procedures.
5. Will remain in country for at least 7 days

Exclusion Criteria:

1. Allergy to rifamycins, quinolones, macrolides, or loperamide (not including mild gastrointestinal upset).
2. Antibiotic therapy in the 72 hours prior to presentation (excluding malaria prophylaxis with mefloquine, malarone, chloroquine/proguanil, or doxycycline).
3. Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, and warfarin).
4. History of seizures (relative contraindication to quinolones)
5. Positive pregnancy test at presentation (contraindicated with fluoroquinolone therapy). All female subjects will be administered a urine pregnancy test prior to enrollment.
6. Presence of symptoms \>96 hours prior to initiating treatment.
7. Use of \>4 mg loperamide or use of any amount of loperamide for greater than 24 hours prior to enrollment.

Primary outcomes:
measure: Clinical Cure - Acute Watery Diarrhea group
timeFrame: 24 hours
measure: Clinical Cure - Acute Dysentery/Febrile Diarrhea group
timeFrame: 48 hours
Secondary outcomes:
measure: Time to Last Unformed Stool
timeFrame: 24, 48, 72 hours
Other outcomes:
Locations:
city: Camp Bastion
country: Afghanistan
facility: UK Role 3 Joint Force Hospital
city: Camp Lemonnier
country: Djibouti
facility: U.S. Naval Expeditionary Base
city: Soto Cano Air Base
country: Honduras
facility: Joint Task Force - Bravo
city: Nanyuki
country: Kenya
facility: British Army Training Unit Kenya
city: Bangkok
country: Thailand
facility: Armed Forces Research Institute of Medical Sciences
Study officials:
affiliation: Naval Medical Research Center
name: Mark Riddle, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.