Trial Evaluating Ambulatory Treatment of Travelers' Diarrhea
Trial Evaluating Ambulatory Treatment of Travelers' 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.
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.
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.