Trial Outcomes & Findings for Studies of COVID-19 Patients Treated With Oral Bismuth Subsalicylate (Pepto-Bismol) (NCT NCT04811339)

NCT ID: NCT04811339

Last Updated: 2023-03-01

Results Overview

Number of bowel movements recorded over the 3 day study. Baseline (BL) /day1 + Day 2 + Day 3

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

3 days

Results posted on

2023-03-01

Participant Flow

The open label feasibility arm started Oct 2020 and completed Feb 2021 at University of Louisville Hospitals. First patient consented and received drug was on Oct 27 2020, last patient Feb 20 2021. This was pre vaccine environment. Public availability of vaccine in Kentucky was March of 2021. 19 patients received drug with only 10 patients completing therapy. Placebo controlled study (50 patients) was cancelled. If started a new study will be entered in Clinical.Trials.gov

19 patients received drug. 9 patients received some Bismuth Subsalicylate (BSS), 10 patients completed 3 days of BSS therapy. All was done in pre-vaccine environment. 25 patients consented received no drug.

Participant milestones

Participant milestones
Measure	BSS Open Label 10 patients will be treated with open label BSS and complete the 3 day therapy. Open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate) 10 patients need to complete this feasibility arm	Consented Only No Drug 25 consented but received no drug. Most were early on in the recruitment of patients.
Overall Study STARTED	19	25
Overall Study Complete 3 Days of BSS	10	0
Overall Study COMPLETED	10	0
Overall Study NOT COMPLETED	9	25

Reasons for withdrawal

Reasons for withdrawal
Measure	BSS Open Label 10 patients will be treated with open label BSS and complete the 3 day therapy. Open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate) 10 patients need to complete this feasibility arm	Consented Only No Drug 25 consented but received no drug. Most were early on in the recruitment of patients.
Overall Study lack of transportation not wanting to return	4	8
Overall Study Adverse Event	3	0
Overall Study Lost to Follow-up	1	0
Overall Study Inconclusive saliva SARS CoV2 test (3X)	1	0
Overall Study Negative primary or secondary salivary SARS-CoV2 test	0	6
Overall Study Medications. Standard of Care medications were changing rapidly Protocol needed constant amending	0	4
Overall Study Withdrawal by Subject	0	3
Overall Study Transferred to ICU for non-COVID-19 related problem	0	1
Overall Study Early on Nurse/Physician communication issue	0	3

Baseline Characteristics

Only those patients who received any BSS had this parameter collected. Those that were consented but received no drug - only had basic demographic information collected

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label BSS Therapy -Completed n=10 Participants All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate) 10 who completed 3 day therapy and provided all samples	Open Label BSS Therapy - Those Who DID NOT Complete n=9 Participants 9 patients who got some BSS - but did not complete 3 day therapy	Open Label - BSS Therapy No BSS Given n=25 Participants Those 25 patients who consented but received no BSS therapy.	Cancelled Placebo-control & BSS Arm The Subsequent 50 patients would have been 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. We could not recruit due to confiscation and expiration of placebo. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=10 Participants	0 Participants n=9 Participants	0 Participants n=25 Participants	—	0 Participants n=44 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=10 Participants	5 Participants n=9 Participants	15 Participants n=25 Participants	—	26 Participants n=44 Participants
Age, Categorical >=65 years	4 Participants n=10 Participants	4 Participants n=9 Participants	10 Participants n=25 Participants	—	18 Participants n=44 Participants
Age, Continuous	52.70 year STANDARD_DEVIATION 21.79 • n=10 Participants	65.22 year STANDARD_DEVIATION 8.84 • n=9 Participants	60.6 year STANDARD_DEVIATION 14.58 • n=25 Participants	—	59.75 year STANDARD_DEVIATION 15.84 • n=44 Participants
Sex: Female, Male Female	5 Participants n=10 Participants	3 Participants n=9 Participants	11 Participants n=25 Participants	—	19 Participants n=44 Participants
Sex: Female, Male Male	5 Participants n=10 Participants	6 Participants n=9 Participants	14 Participants n=25 Participants	—	25 Participants n=44 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=9 Participants	0 Participants n=25 Participants	—	0 Participants n=44 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants	0 Participants n=9 Participants	0 Participants n=25 Participants	—	0 Participants n=44 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=9 Participants	1 Participants n=25 Participants	—	1 Participants n=44 Participants
Race (NIH/OMB) Black or African American	2 Participants n=10 Participants	2 Participants n=9 Participants	7 Participants n=25 Participants	—	11 Participants n=44 Participants
Race (NIH/OMB) White	8 Participants n=10 Participants	7 Participants n=9 Participants	17 Participants n=25 Participants	—	32 Participants n=44 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=9 Participants	0 Participants n=25 Participants	—	0 Participants n=44 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=9 Participants	0 Participants n=25 Participants	—	0 Participants n=44 Participants
Region of Enrollment United States	10 Participants n=10 Participants	9 Participants n=9 Participants	25 Participants n=25 Participants	—	44 Participants n=44 Participants
Number of pre-existing Comorbidities	3.7 Comorbidities n=10 Participants • Only those patients who received any BSS had this parameter collected. Those that were consented but received no drug - only had basic demographic information collected	4.7 Comorbidities n=9 Participants • Only those patients who received any BSS had this parameter collected. Those that were consented but received no drug - only had basic demographic information collected	—	—	4.2 Comorbidities n=19 Participants • Only those patients who received any BSS had this parameter collected. Those that were consented but received no drug - only had basic demographic information collected
Number of pre-existing home medications	3.8 Home medications n=10 Participants • Only those who received any BSS had this measure collected. Those consented but who received not drug did not have this parameter collected	4.8 Home medications n=9 Participants • Only those who received any BSS had this measure collected. Those consented but who received not drug did not have this parameter collected	—	—	4.4 Home medications n=19 Participants • Only those who received any BSS had this measure collected. Those consented but who received not drug did not have this parameter collected
Number of COVID-19 symptom days prior to study entry	8.5 days n=10 Participants • Only those who received any BSS had this parameter collected. Those consented but had received no BSS did not have this parameter collected	9.1 days n=9 Participants • Only those who received any BSS had this parameter collected. Those consented but had received no BSS did not have this parameter collected	—	—	10.6 days n=19 Participants • Only those who received any BSS had this parameter collected. Those consented but had received no BSS did not have this parameter collected
Number of COVID-19 morbidities	3.5 COVID-19 related morbidities n=10 Participants • Only those patients who received drug had this parameter measured. Those who were consented but received no drug did not have this parameter measured	2.4 COVID-19 related morbidities n=9 Participants • Only those patients who received drug had this parameter measured. Those who were consented but received no drug did not have this parameter measured	—	—	3 COVID-19 related morbidities n=19 Participants • Only those patients who received drug had this parameter measured. Those who were consented but received no drug did not have this parameter measured
Baseline/Day1 5 symptom score	3.8 Scores on a Scale n=10 Participants • Only patients who received any BSS had this parameter measured. Those consented but who did not receive BSS did not have this parameter recorded	3.2 Scores on a Scale n=9 Participants • Only patients who received any BSS had this parameter measured. Those consented but who did not receive BSS did not have this parameter recorded	—	—	3.5 Scores on a Scale n=19 Participants • Only patients who received any BSS had this parameter measured. Those consented but who did not receive BSS did not have this parameter recorded
Baseline/Day1 3 symptom score	2.4 Scores on scale n=10 Participants • Parameter recorded only for those patients who received any BSS. Those patients consented who did not receive BSS did not have this parameter recorded	2.1 Scores on scale n=9 Participants • Parameter recorded only for those patients who received any BSS. Those patients consented who did not receive BSS did not have this parameter recorded	—	—	2.4 Scores on scale n=19 Participants • Parameter recorded only for those patients who received any BSS. Those patients consented who did not receive BSS did not have this parameter recorded
Baseline Health Score	9.3 scores on scale n=10 Participants • This score was calculated for those patients who received any drug. Those patients who consented but did not receive any medication did not have this score calculated.	9.1 scores on scale n=9 Participants • This score was calculated for those patients who received any drug. Those patients who consented but did not receive any medication did not have this score calculated.	—	—	9.2 scores on scale n=19 Participants • This score was calculated for those patients who received any drug. Those patients who consented but did not receive any medication did not have this score calculated.

PRIMARY outcome

Timeframe: 3 days

Population: Data from 10 completed patients.

Number of bowel movements recorded over the 3 day study. Baseline (BL) /day1 + Day 2 + Day 3

Outcome measures

Outcome measures
Measure	Open Label BSS Completed Patients n=10 Participants All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)	SOC Control Group 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. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)
Measure of Daily Stool Frequency for Patients With COVID Treated With Bismuth	3 bowel movements Standard Error 0.5	—

SECONDARY outcome

Timeframe: Day 3 - or 48 hours after starting BSS

Population: These 10 patients completed BSS therapy and provided 3 days of saliva for RT-LAMP testing for presence or absence of SARS-CoV2

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)

Outcome measures

Outcome measures
Measure	Open Label BSS Completed Patients n=10 Participants All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)	SOC Control Group 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. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)
Salivary SARS-CoV2 Day 3 Status Using Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Those who cleared salivary SARS-CoV2	5 Participants	0 Participants
Salivary SARS-CoV2 Day 3 Status Using Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Those who remained salivary SARS-CoV2 positive	5 Participants	0 Participants

POST_HOC outcome

Timeframe: The score was taken at BL (baseline)/day 1, Day 2 ( 24 hours after BSS started ) and Day 3 (48 hours after BSS started). This Outcome is Day 3 score.

Population: Those 10 patients who completed BSS open label therapy

The 5 symptom composite score was generated from 5 symptoms: Cough, Headache, Fatigue, Shortness of Breath, and Anosmia (no smell). Each symptom was scored as such: 0 was not affected, 1 was little affected, 2 moderately affected, 3 severely affected. A composite score was generated using the score given for each individual symptom, ie. the sum of symptomatic score of Cough + symptomatic score of Headache + symptomatic score of Fatigue + symptomatic score of Shortness of Breath + symptomatic score of anosmia. The maximum and most symptomatic composite score could be 15 each day. The minimum score could be 0. This score was calculated calculated for BL/day1, day 2 and day 3 . This outcome is the composite 5 symptom score on day 3.

Outcome measures

Outcome measures
Measure	Open Label BSS Completed Patients n=10 Participants All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)	SOC Control Group 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. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)
Day 3 Composite 5 Symptom Score	2.9 score on a scale Interval 0.0 to 7.0	—

POST_HOC outcome

Timeframe: This is the day 3 composite score

Population: These 10 patients completed the open label BSS study

The 3 symptom composite score was generated from 3 symptoms: Cough, Headache, and Fatigue. Each symptom was scored as such: 0 was not affected, 1 was little affected, 2 moderately affected, 3 severely affected. A composite score was generated using the score given for each individual symptom, ie. the sum of symptomatic score of Cough + symptomatic score of Headache + symptomatic score of Fatigue. The maximum and most symptomatic composite score could be 9 each day. The minimum score could be 0 . This score was calculated calculated for BL/day1, day 2 and day 3 . This outcome is the composite 3 symptom score on day 3.

Outcome measures

Outcome measures
Measure	Open Label BSS Completed Patients n=10 Participants All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)	SOC Control Group 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. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)
Day 3 Composite 3 Symptom Score	1.4 score on a scale Interval 0.0 to 4.0	—

Adverse Events

Open Label BSS Therapy -Completed

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Open Label BSS Therapy - Those Who DID NOT Complete

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cancelled SOC Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Open Label BSS Therapy -Completed n=10 participants at risk All patients will be assigned to the treatment group for the first 10 patients treated with open label BSS. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate) 10 who completed 3 day therapy and provided all samples	Open Label BSS Therapy - Those Who DID NOT Complete n=9 participants at risk 9 patients who got some BSS - but did not complete 3 day therapy	Cancelled SOC Control Group This group was cancelled. The Subsequent 50 patients would have been 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. open label BSS (pepto Bismol): Pepto bismol (bismuth subsalicylate)
Gastrointestinal disorders Abdominal bloating	0.00% 0/10 • Adverse events were collected during the 3 days of the BSS study. Patients were asked to report any side effects	33.3% 3/9 • Number of events 3 • Adverse events were collected during the 3 days of the BSS study. Patients were asked to report any side effects	— 0/0 • Adverse events were collected during the 3 days of the BSS study. Patients were asked to report any side effects

Additional Information

Dr. Bruce Yacyshyn

University of Cincinnati

Phone: 513-633-8715

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place