Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea (TrEAT TD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Uniformed Services University of the Health Sciences
Sponsor:
Collaborators:
Navy Bureau of Medicine and Surgery
United Kingdom Ministry of Defence
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
Information provided by (Responsible Party):
Mark Riddle, CDR, MC, USN, Naval Medical Research Center
ClinicalTrials.gov Identifier:
NCT01618591
First received: June 1, 2012
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention
Acute Watery Diarrhea
Dysentery/Febrile Diarrhea
Drug: Single dose rifaximin 1650 mg
Drug: Single dose azithromycin 500 mg
Drug: Single dose levofloxacin 500 mg
Drug: Single dose azithromycin 1000 mg plus loperamide
Drug: Single dose azithromycin 1000 mg plus placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Uniformed Services University of the Health Sciences:

Primary Outcome Measures:
  • Clinical Cure - Acute Watery Diarrhea group [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    • 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


Secondary Outcome Measures:
  • Time to Last Unformed Stool [ Time Frame: 24, 48, 72 hours ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 510
Study Start Date: September 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acute Watery Diarrhea Drug: Single dose rifaximin 1650 mg
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
Drug: Single dose azithromycin 500 mg
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
Drug: Single dose levofloxacin 500 mg
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
Experimental: Acute Dysentery/Febrile Drug: Single dose azithromycin 1000 mg plus loperamide
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
Drug: Single dose azithromycin 1000 mg plus placebo
Azithromycin 1000 mg as a single dose and placebo in lieu of loperamide

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01618591

Contacts
Contact: Mark Riddle, MD, DrPH 301-319-7686 mark.riddle@med.navy.mil
Contact: David Tribble, MD, DrPH 301-295-1422 dtribble@idcrp.org

Locations
Afghanistan
UK Role 3 Joint Force Hospital Completed
Camp Bastion, Afghanistan
Djibouti
U.S. Naval Expeditionary Base Suspended
Camp Lemonnier, Djibouti
Honduras
Joint Task Force - Bravo Recruiting
Soto Cano Air Base, Honduras
Contact: Ricardo Aviles, MD    +505 9992 3491    ricardo.aviles.hn@jtfb.southcom.mil   
Kenya
British Army Training Unit Kenya Recruiting
Nanyuki, Kenya
Contact: Patrick Connor, FRCP, MCGI, AGAF, MIHM    +447515397082    pconnor@nhs.net   
Principal Investigator: Patrick Connor, FRCP, MCGI, AGAF, MIHM         
Sponsors and Collaborators
Uniformed Services University of the Health Sciences
Navy Bureau of Medicine and Surgery
United Kingdom Ministry of Defence
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
Investigators
Principal Investigator: Mark Riddle, MD, DrPH Naval Medical Research Center
  More Information

No publications provided

Responsible Party: Mark Riddle, CDR, MC, USN, Head, Enteric Diseases Department, Naval Medical Research Center
ClinicalTrials.gov Identifier: NCT01618591     History of Changes
Other Study ID Numbers: IDCRP-065
Study First Received: June 1, 2012
Last Updated: October 9, 2014
Health Authority: United States: Uniformed Services Infectious Disease Institutional Review Board
United Kingdom: Ministry of Defence Ethics and Review Committee
Kenya: Kenya Medical Research Institute Institutional Review Board
United States: Federal Government

Keywords provided by Uniformed Services University of the Health Sciences:
diarrhea
travelers' diarrhea
watery diarrhea
enteric illness
dysentery
gastrointestinal

Additional relevant MeSH terms:
Diarrhea
Dysentery
Signs and Symptoms, Digestive
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Azithromycin
Levofloxacin
Ofloxacin
Rifaximin
Loperamide
Antidiarrheals
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 19, 2014