Bismuth Subsalicylate's Role in the Prevention of Travelers' Diarrhea

Bismuth Subsalicylate's Role in the Prevention of Travelers' Diarrhea and Impact on Acquisition of Gut Antimicrobial Resistance Genes

The purpose of this study is to determine if the use of prophylactic bismuth subsalicylate (BSS) has an effect on the acquisition of travelers' diarrhea (TD) or antimicrobial resistance (AMR) genes in fecal samples among international travelers who departed from the United States to South East Asia, South Central Asia, or Africa. Our hypotheses will be tested using a double-blinded, placebo controlled randomized clinical trial with participants from a pre-travel health clinic in the United States.

Study Overview

• Status: Terminated
• Conditions: Antibiotic Resistant Infection; Diarrhea Travelers
• Intervention / Treatment: Drug: Bismuth subsalicylate; Drug: Placebo

Detailed Description

This study is a double-blind, placebo-controlled randomized clinical trial designed to evaluate the effectiveness of bismuth subsalicylate (BSS) in preventing travelers' diarrhea (TD) and its potential impact on the acquisition of antimicrobial resistance (AMR) genes and changes in the gut microbiome among international travelers.

Adult participants (18-69 years) planning travel from the United States to high-risk regions, including South East Asia, South Central Asia, and Africa, will be recruited from a pre-travel health clinic. Eligible participants will be randomized to receive either BSS (4 tablets twice daily; total daily dose approximately 2.1 g) or a matching placebo. Study medication will begin prior to arrival at the destination and continue throughout the duration of travel (up to 21 days).

Participants will complete standardized questionnaires before travel, daily during travel, and after returning to the United States. These questionnaires will capture information on medication adherence, gastrointestinal symptoms, development of TD, healthcare utilization, and adverse events. TD will be defined as three or more unformed stools within a 24-hour period, with or without associated symptoms.

To evaluate secondary objectives, participants will provide stool samples within 7 days prior to departure and within 10 days after return. These samples will be analyzed to assess acquisition of AMR genes using molecular methods and to evaluate changes in the gut microbiome, including the presence of enteric pathogens.

The primary objective is to determine whether prophylactic BSS reduces the incidence of TD among international travelers. Secondary objectives include assessing the impact of BSS on acquisition of AMR genes and evaluating changes in the gut microbiome associated with travel and intervention use.

Participants will be followed from enrollment through completion of post-travel data collection, with a total participation duration of approximately 4-6 weeks. Safety will be monitored through participant-reported adverse events collected during and after travel.

This study aims to provide evidence on a low-cost, widely available preventive strategy for TD and to better understand its potential role in reducing the spread of antimicrobial resistance associated with international travel.

• Study Type: Interventional
• Enrollment (Actual): 482
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10022
      • Marina Rogova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Be ≥ 18 and <70 years of age at the time of enrollment
2. Sign an informed consent stating willingness to participate and comply with the study protocol
3. Plan on leaving for an international trip ≥7 days after their pre-travel consultation
4. Plan on traveling in country for ≥7 days but ≤21 days (21 day limit due to BSS duration recommendations and a lack of data on longer-term BSS use)
5. Traveling to either South East Asia, South Central Asia, North Africa, or Sub-Saharan Africa for at least 7 days of their itinerary
6. Be willing to complete an initial eligibility screening
7. Be willing to complete questionnaires and provide biologic specimens (stool) within 7 days of departure and within 10 days after return
8. Be willing to refrain from taking any pre-biotics, probiotic, synbiotic and/or herbal supplements throughout their study period

Exclusion Criteria:

1. Are <18 years of age or >69 years of age
2. Are traveling in country for <7 or >21 days
3. Have known or suspected contraindications to taking BSS (including, but not limited to, travelers with kidney disease, diabetes, gout, a clotting disorder, or an allergy to any component of BSS)
4. Are pregnant (via self-report), are planning to become pregnant, or may become pregnant during travel (not actively using contraception and are sexually active), or are breastfeeding
5. Routinely take a medication known to interact with BSS (including, but not limited to, insulin, methotrexate, valproic acid, angiotensin-converting enzyme inhibitors, anticoagulants, or other salicylates)
6. Have taken an antibiotic in the 30 days before departure
7. Have taken any medications that may lower one's ability to fight infection (e.g., steroids, monoclonal antibodies, etc.)
8. Have previous diagnoses of immunocompromising conditions such as HIV/AIDS, complement deficiency, immunoglobulin deficiency, or undergoing active chemotherapy or participants with chronic gastrointestinal disorders, such as chronic diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), celiac disease, malabsorption syndromes, pancreatic insufficiency, gallbladder disease, or current gastrointestinal cancer
9. Have had diarrhea anytime in the previous 30 days, have diarrhea at the pre-travel consultation, or develop diarrhea before departure
10. Have been given doxycycline for malaria prophylaxis for the current trip (due to possible drug-drug interactions and decreased absorption of the doxycycline)
11. Have an allergy to any component of the placebo tablets

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention Group; Bismuth subsalicylate 4 tablets po bid (2.1 grams total of BSS)	Drug: Bismuth subsalicylate; Bismuth subsalicylate administered orally as tablets (4 tablets twice daily; total daily dose approximately 2.1 g) beginning prior to arrival at the travel destination and continued throughout the duration of travel (up to 21 days).; Other Names: Pepto Bismol
Placebo Comparator: Placebo; Placebo oral tablet 4 bid	Drug: Placebo; Matching oral placebo tablets administered twice daily, identical in appearance, taste, and packaging to bismuth subsalicylate, given for the duration of travel (up to 21 days).; Other Names: Placebo Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Traveler's Diarrhea	Incidence of travelers' diarrhea, defined as self-reported occurrence of three or more unformed stools within a 24-hour period with or without associated gastrointestinal symptoms during travel or within 10 days after return.	Change from baseline through 10 days post-travel

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut AMR Genes	Pre- and post-travel stools will be tested for the presence/absence of AMR genes. Data for this outcome measure are not yet analyzed. Results will be submitted when analyses are complete.	Once within 7 days (before travel); once within 10 days (after travel)

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: Procter and Gamble; The New York Center for Travel and Tropical Medicine
• Investigators: Principal Investigator: Bradley Connor, MD, The New York Center for Travel and Tropical Medicine

Publications and helpful links

General Publications

• Gibb RD, Brum JM, Sloan KJ, Pitz AM, Circello BT, Grayling RA. Revisiting the efficacy of bismuth subsalicylate for the prevention of traveller's diarrhoea. J Travel Med. 2025 Oct 1;32(6):taaf076. doi: 10.1093/jtm/taaf076.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2018
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): April 29, 2026

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Dicarboxylic Acids; Succinates; Dioctyl Sulfosuccinic Acid; bismuth subsalicylate
• Other Study ID Numbers: 7082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No