1. ABSTRACT

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 US and UK 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 16mg/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 16mg/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 16mg/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 16mg/day for 2 days (75 subjects); or (2) azithromycin 1000 mg as a single dose without loperamide (75 subjects). 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 7days. In addition, microbiological cure will be evaluated at 7days 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-days .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-day visit, and those who opt for the additional follow-up will complete a series of web-based surveys at 3-, 6-, 9-, and 12-months post enrollment. AWD - The primary efficacy end point will be the proportion of patients achieving clinical cure at 24-hrs post-first treatment dose. ADF - The primary efficacy end point will be the proportion of patients achieving clinical cure at 48-hrs post first treatment dose.