DiarrheaPhase 4SABER-CNCT04811339

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

A Phase 4 study testing Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable in people with Diarrhea and COVID-19, run by University of Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Diarrhea, COVID-19
What is being tested?: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 60 participants
Where: 1 siteUnited States
Study dates: 27 Oct 2020to 15 Aug 2021
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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.

Show all 14Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Louisville
Louisville, Kentucky, 40202

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Diarrhea, COVID-19
Being tested: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable, Placebo oral tablet without BSS
Medical subject headings: Diarrhea, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, ChewableDrug
Also called Pepto Bismol
Pepto bismol (bismuth subsalicylate)
Placebo oral tablet without BSSOther
Placebo Tablet made by P \& G to contain everything except active ingredient ( BSS)

Study groups in NCT04811339
Study group	Role	What they receive
Open label BSS	Experimental	All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. Receives: Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable
Randomized BSS or Placebo	Placebo comparator	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. Receives: Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable; Other: Placebo oral tablet without BSS

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 3 days

Secondary outcomes (1)

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)
Measured: Day 3 - or 48 hours after starting BSS

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Oct 202015 Aug 2021

First posted23 Mar 2021
Study start27 Oct 2020
Primary completion15 Aug 2021
Study completion15 Aug 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DiarrheaStudies of the same condition, open and under way.
More trials run by University of CincinnatiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Open label trial of Bismuth subsalicylate (10 patients) followed by a second, placebo controlled study (50 patients) for mild to moderate COVID-19+ patients.
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04811339
Sponsor's protocol ID: SABER-C 20.0636
Acronym: SABER-C
Status last verified: Feb 2023
First submitted: 20 Mar 2021
Last updated: 1 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 35370296
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.
PubMed 32772204

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT04811339
Acronym / sponsor ID: SABER-C / SABER-C 20.0636
Conditions: Diarrhea, COVID-19
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: University of CincinnatiUniversity, hospital or other
Collaborators: Procter and Gamble
Study start: 27 Oct 2020 (actual)
Primary completion: 15 Aug 2021 (actual)
Study completion: 15 Aug 2021 (actual)
First posted: 23 Mar 2021 (actual)
Results: Posted 1 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: Open label trial of Bismuth subsalicylate (10 patients) followed by a second, placebo controlled study (50 patients) for mild to moderate COVID-19+ patients.

Arm	Type	Receives
Open label BSS	Experimental	Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, ChewableAll patients will be assigned to the treatment group for the first 10 patients treated with open label BSS.
Randomized BSS or Placebo	Placebo comparator	Drug: Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable, Other: Placebo oral tablet without BSSThe 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.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, ChewableAlso: Pepto BismolPepto bismol (bismuth subsalicylate)	Drug	Open label BSS, Randomized BSS or Placebo
Placebo oral tablet without BSSPlacebo Tablet made by P \& G to contain everything except active ingredient ( BSS)	Other	Randomized BSS or Placebo

Primary outcome

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

1 secondary outcome

Salivary SARS-CoV2 Day 3 Status Using Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP)
Time frame: Day 3 - or 48 hours after starting BSS

Results and safety

Results posted to the registry on 1 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BSS Open Label	19	10
Consented Only No Drug	25	0
SOC Control Group - Cancelled	0	0

Primary outcome: Measure of Daily Stool Frequency for Patients With COVID Treated With Bismuth

Time frame: 3 days. Mean (Standard Error). Unit: bowel movements

Measure	Open Label BSS Completed Patients n = 10	SOC Control Group n = 0
Value	3 (0.5)	–

Population analysed: Data from 10 completed patients.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected during the 3 days of the BSS study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Open Label BSS Therapy -Completed	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Open Label BSS Therapy - Those Who DID NOT Complete	0 of 9 (0%)	3 of 9 (33.3%)	0 of 9
Cancelled SOC Control Group	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): 1. Changing Standard of Care. 2. Patients, floor nurses and coordinators did not always keep track of number of pills taken. 3. For better compliance, we needed to decrease number of pills/day from 24 or 8 per day. 4. Transportation after discharge and sample collection needed to be optimized. 5. There was surprising difficulty in recruiting and maintaining patients in the trial during the first year, prior to general vaccine availability. 25 patients consented and never received drug.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 35370296Yacyshyn 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.
Background: PubMed 32772204Brum 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.
Individual participant dataSharing planned: No

Related trials for Diarrhea

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bruce Yacyshyn, MD principal investigator

Adjunct Professor Systems Physiology and Pharmacology University of Cincinnati

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Bismuth Subsalicylate 262 milligram (mg) Oral Tablet, Chewable in people with Diarrhea and COVID-19, run by University of Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measure of Daily Stool Frequency for Patients With COVID Treated With Bismuth (time frame: 3 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04811339, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.