632 - A Randomized, Placebo-Controlled, Double-Blind, Clinical Trial Evaluating Two Dose Regimens of Rifaximin (550mg daily or twice-daily) for Chemoprophylaxis Against Travelers’ Diarrhea Among Deployed U.S. and U.K. Military Personnel (PREVENT TD)

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Presenting Author(s)

Ramiro L. Gutierrez

Head, Enteric Diseases Department; Adjunct Faculty Infectious Disease Fellowship, Walter Reed National Military Medical Center
Naval Medical Research Center, Silver Spring, Maryland; Uniformed Services University of the Health Sciences, Bethesda, MD
Gaithersburg, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

DB

Daniel Burns

Dr.
UK Ministry of Defence
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TL

Tahaniyat Lalani

Research Physician, IDCRP Research Area Director, Associate Professor USU
Naval Medical Center Portsmouth
Portsmouth, Virginia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DB

Denise Bennett-Carter

CRC
Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JF

Jamie A. Fraser

Head Clinical Research Manager
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MR

Mark Riddle

Associate Dean for Clinical Research
University of Nevada, Reno School of Medicine
Reno, Nevada
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PC

Patrick Connor

Director
Royal Centre for Defense Medicine
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CP

Chad Porter

Branch Head
Naval Medical Research Center
Silver Spring, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TT

Thomas Troth

Consultant Registrar
Royal Centre for Defense Medicine
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RR

Richard Ruck

DCCS
US Army
Honolulu, Hawaii
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JB

Jerry Barton

Director
US Army
Honolulu, Hawaii
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DT

Drake H. Tilley

Staff Physician
Naval Medical Center San Diego
San Diego, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AK

Anjali Kunz

TY Program Director, Peds ID
Madigan Army Medical Center
Tacoma, WA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MF

Mary P. Fairchok

Clinical Investiagtor
Madigan Army Medical Center
Takoma, Washington
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Heather Yun

Deputy Commander for Medical Services; Professor of Medicine
Infectious Diseases, Brooke Army Medical Center
San Antonio, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BA

Bryan Alvarez

Director
Naval Hospital Camp Lejeune
Jacksonville, North Carolina
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RH

Robert Higgins

Director
Naval Hospital Camp Lejeune
Jacksonville, North Carolina
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
IM

Indrani Mitra

Analyst
Henry M. Jackson Foundation for the Advancement of Military Medicine; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences
Bethesda, MD
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Laveta Stewart

Epidemiologist
Infectious Disease Clinical Research Program, Henry Jackson Foundation
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AR

Azizur Rahman

Statistitian
Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JR

JoAnna Rimmer

Director
Royal Centre for Defense Medicine
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
EH

Emma Hutley

Director
Royal Centre for Defense Medicine
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BS

Brett Swierczewski

Director
Walter Reed Army Institute of Research
Silver Spring, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BT

Bethany Tabberer

CRC
Royal Centre for Defense Medicine
Birmingham, England, United Kingdom
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DT

David R. Tribble

Science Director, Infectious Disease Clinical Research Program
Uniformed Services University of the Health Sciences
Bethesda, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: Travelers’ diarrhea (TD) is a leading threat to military readiness. Most trials of rifaximin chemoprophylaxis involve civilians or short-duration travel, whereas military travelers are exposed for longer periods at austere locations and are often physically taxed. We sought to assess efficacy of two regimens among military personnel deployed overseas.

Methods: This was a multi-site, double-blind, placebo-controlled trial of deployed military, randomized to placebo, rifaximin 550 mg daily, or rifaximin 550 mg twice-daily, for up to 42 days (1:1:1; 6 randomizations/block). Diaries were reviewed with subjects on return. Primary endpoint was time to first unformed stool (TFUS) in a TD episode. Other endpoints were assessed by intention to treat (ITT) and subgroups included incidence of any loose stool, meeting criteria for TD, safety, efficacy, adherence and impact to activity endpoints.

Results: 343 subjects were included in the ITT population. All UK travelers deployed to a single-site in Kenya; US travelers mostly deployed to various Asia-Pacific locations. Of 73 (21.2%) subjects reporting diarrhea, 42 (57.5%) met TD criteria. Among rifaximin-treated subjects, 15.9% (n=17) reported diarrhea in the twice-daily arm, 20.7% (n=25) in the daily arm, vs. 27.0% (n=31) of placebo recipients; p=.04 and 0.26 respectively. TD was reported by 10.3% (n=11) and 10.7% (n=13) in the daily and twice-daily arms, vs. 15.7% (n=18) among placebo recipients; p=0.24 vs. 0.26 respectively. Among UK personnel, a twice-daily regimen vs. placebo resulted in significantly fewer TD episodes (1.6% vs. 11.9%; p=0.03). Adverse events were similar between groups.Table 1: Demographics, endpoints, and adverse events (Comparisons are across placebo vs. each dosing regimen. Intent-to-treat [ITT] population defined as subjects enrolled into the study, randomized, travelled and had follow-up. p-values calculated from chi-square or Fisher’s exact test [categorical variables] and Wilcoxon-Mann-Whitney test [continuous variables]. Analyses performed on SAS v9.4. BID: twice-daily)

Conclusion: This is the first trial comparing two high-dose regimens of rifaximin prophylaxis in deployed personnel. Unlike prior reports, neither regimen was associated with an overall significant decrease in TD, potentially due to low overall TD incidence. However, the twice-daily regimen was associated with a numerically lower incidence of diarrheal stool, and in the UK subject group, there was a significant decrease of both TD and diarrheal stool. The impact of variability in regional TD risk, pathogen distribution and adherence in austere deployment environments on efficacy will be reviewed.