Studies of COVID-19 Patients Treated With Oral Bismuth Subsalicylate (Pepto-Bismol) (SABER-C)

Pilot and Randomized, Controlled Studies to Assess Stool Frequency of COVID + Patients Treated With Oral Bismuth Subsalicylate (Pepto-Bismol): SABER-C and Lite-SABER-C (Specific Administration of Bismuth for Early Recovery of COVID-19)

The Center for Disease Control (CDC) and World Health Organization (WHO) have deemed the COVID-19 virus a global pandemic of unprecedented severity in modern times. In 2019, this novel Coronavirus (COVID-19) emerged from the Asian continent and has now caused upwards of 1million deaths and over 6 million infections globally. Currently, the estimated global economic impact is over 5 Trillion dollars. Understanding the host response to pathogens, specifically the cellular and humoral responses, has played an important role in new non-antibiotic therapies. Bismuth subsalicylate (Pepto-Bismol) has a potential role in the clearance and/or recurrence of enteric viral infections.

Study Overview

• Status: Completed
• Conditions: COVID-19; Diarrhea
• Intervention / Treatment: Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable; Other: Placebo oral tablet without BSS

Detailed Description

Readily available over-the-counter (OTC) medication for symptomatic relief and appropriate oral hydration can be health saving measures of great convenience for those affected by enteric bacterial and viral infections. BSS is a non-proprietary monograph product that is available in the USA and abroad, over-the-counter (OTC). Of all OTC medications for traveller's diarrhea (TD), bismuth subsalicylate (BSS) has the greatest antimicrobial activity against pathogenic bacteria .BSS has also exhibited significant inhibition on viral invasion of host cells and viral efficacy. Both BSS and bismuth oxychloride (BiOCl, which is formed in the stomach after ingestion of BSS) at low concentration (0.004-0.13mg/mL) significantly reduced norovirus (NoV) RNA levels, suggesting an in vivo antiviral mechanism. BSS has also been shown to have antiviral activity since it inhibited replication of 4 strains of rotavirus in tissue culture cells and caused a dose-dependent reduction in the growth of several enteric viruses.

Historically, BSS has been indicated and effectively used for the treatment of TD or enteric infection, mainly when vomiting occurs. Although the safety and efficacy of BSS is well known, some of the research done with BSS resides within the industry and have not been published. We have recently completed an extensive meta-analysis using unpublished clinical studies regarding BSS safety and efficacy. Meta-analyses of randomized controlled clinical trials were performed with studies specifically designed to capture prevention of manifestation and relief of diarrhea.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be eligible to participate in the study, patients must meet the following criteria: Ability to provide written or remote informed consent (telephone and DocuSign) Ability to comply with study requirements, Men or women 18 to 85 years of age, inclusive Current diagnosis of an initial occurrence of non-severe, non-complicated COV+ infection as defined by:

• Presence COVID-19 in the saliva using point of care (POC) Qualitative real time - polymerase chain reaction (QRT- PCR) assay.
• Management in an outpatient (i.e., non-hospital) or inpatient setting NOT on a ventilator.
• Alert and awake
• Able to chew the study drug completely.
• Women should fulfill one of the following criteria:
• Answer in the affirmative that "they are not or could not be pregnant"
• Post-menopausal; either amenorrhea ≥12 months or follicle stimulating hormone >20 mIU/mL (milli-International units)
• Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation.
• Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from Screening through the 21 Day visit, per Section 10.2.

Standard of care COVID-19 treatment is acceptable.

Exclusion Criteria:

Patients with any of the following will be excluded from admission into the study:

• Existence of an intra-abdominal abscess, enteric fistula, or symptomatic bowel obstruction
• History of allergy to salicylates.
• History of short gut syndrome, active ulcer or recent history of GI bleeding or melena.
• Systemic chemotherapy for the treatment of cancer during the 60 days prior to consent or planned during the study
• Active use of remdesivir.
• vaccination for COVID within 30 days.
• Current use of drugs that control diarrhea or affect peristalsis (e.g., loperamide. Opiates can be used in hospitalized patients and with outpatients if they are prescribed to a patient), or any anticipated use during the study
• Active drug, chemical, or alcohol dependency as determined by Investigator through history or urine toxicology screen
• Enrollment in any other investigational drug or device study known to interfere with Pepto bismol (bismuth subsalicylate) within the GI tract, within 30 days prior to Randomization (Day 1) or within 5 half-lives of the last dose of the previous investigational compound, whichever is longer. Vaccines are not exclusionary as they do not interfere with the mechanism of the study drug.
• Severe acute illness unrelated to COVID-19
• Pregnant, breast-feeding, or considering becoming pregnant during the study
• Planned hospitalization or surgery during the study
• Any medical, psychiatric, social, or other circumstances that may interfere with study compliance, completion, or accurate assessment of study outcomes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label BSS; All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS.	Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable; Pepto bismol (bismuth subsalicylate); Other Names: Pepto Bismol
Placebo Comparator: Randomized BSS or Placebo; The Subsequent 50 patients will be randomized to either placebo or BSS. The patients will be assigned by envelope containing a symbol for either active drug or placebo (or other suitable randomization event) by a member of the research team not directly involved in the clinical trial.	Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable; Pepto bismol (bismuth subsalicylate); Other Names: Pepto Bismol; Other: Placebo oral tablet without BSS; Placebo Tablet made by P & G to contain everything except active ingredient ( BSS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Daily Stool Frequency for Patients With COVID Treated With Bismuth	Number of bowel movements recorded over the 3 day study. Baseline (BL) /day1 + Day 2 + Day 3	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary SARS-CoV2 Day 3 Status Using Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP)	Salivary SARS-CoV2 measured daily. The final outcome is SARS-CoV2 status on day 3. Clearance of SARS-CoV2 ( a negative salivary SARS-CoV2 RT-LAMP test). or Remained SARS-CoV2+ ( a positive salivary SARS-CoV2. RT-LAMP test)	Day 3 - or 48 hours after starting BSS

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Procter and Gamble
• Investigators: Principal Investigator: Bruce Yacyshyn, MD, Adjunct Professor Systems Physiology and Pharmacology University of Cincinnati

Publications and helpful links

General Publications

• Yacyshyn MB, Collins J, Chua M, Siegwald A, Yacyshyn S, Briones-Pryor V, Yacyshyn B. Feasibility study of Bismuth Subsalicylate (BSS) as an addition to standard of care for COVID-19 therapy. Curr Ther Res Clin Exp. 2022;96:100667. doi: 10.1016/j.curtheres.2022.100667. Epub 2022 Mar 30. No abstract available.
• Brum JM, Gibb RD, Ramsey DL, Balan G, Yacyshyn BR. Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea. Dig Dis Sci. 2021 Jul;66(7):2323-2335. doi: 10.1007/s10620-020-06509-7. Epub 2020 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Actual): August 15, 2021
• Study Completion (Actual): August 15, 2021

Study Registration Dates

• First Submitted: March 20, 2021
• First Submitted That Met QC Criteria: March 21, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Signs and Symptoms, Digestive; COVID-19; Diarrhea; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Antidiarrheals; Bismuth; Bismuth subsalicylate
• Other Study ID Numbers: SABER-C 20.0636

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.: Yes