COVID-19 PEP: Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT04308668
• Collaborator: McGill University Health Centre/Research Institute of the McGill University Health Centre (Other), University of Manitoba (Other), University of Alberta (Other)
• Enrollment: 1,312
• Locations: 5
• Arms: 2
• Actual Duration (Months): 2.1
• Patients Per Site: 262.4
• Patients Per Site Per Month: 124.8

Study Details

Study Description

Brief Summary

Study Objective:

1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.

2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

Condition or Disease	Intervention/Treatment	Phase
Corona Virus Infection; Acute Respiratory Distress Syndrome; SARS-CoV Infection; Coronavirus; Coronavirus Infections	Drug: Hydroxychloroquine; Other: Placebo	Phase 3

Detailed Description

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. The current strategy uses a public health model of identifying infected cases, isolation, and quarantine to stop transmission. Once exposed, observation is standard-of-care. Therapy is generally not given to persons who are not hospitalized. The doses of hydroxychloroquine being used are within the normal standard FDA-approved doses.

Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or early preemptive therapy may decrease disease severity. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis to prevent disease or preemptive therapy for those with early symptoms. People around the the United States and Canada can participate to help answer this critically important question. No in-person visits are needed.

This trial is targeting 5 groups of people NATIONWIDE to participate:

1. If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR

2. If you live with someone who has been diagnosed with COVID-19, with your last exposure within the last 4 days, and do not have any symptoms; OR

3. If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR

4. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days and do not have symptoms; OR

5. If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days AND have compatible symptoms starting within the last 4 days;

You may participate if you live anywhere in the United States (including territories) or in the Canadian Provinces of Quebec, Manitoba, Alberta, or Ontario.

For information on how to participate in the research trial, go to covidpep.umn.edu or email [e-mail] for instructions. Please check your spam folder if you email.

In Canada, for trial information, please go to: www.covid-19research.ca

Study Design

• Study Type: Interventional
• Actual Enrollment: 1312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Asymptomatic participants are randomized and analyzed separate from symptomatic participants.Asymptomatic participants are randomized and analyzed separate from symptomatic participants.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
• Actual Study Start Date: Mar 17, 2020
• Actual Primary Completion Date: May 20, 2020
• Actual Study Completion Date: May 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Participants in this arm will receive the study drug.	Drug: Hydroxychloroquine; 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days; Other Names: Plaquenil
Placebo Comparator: Placebo Participants in this arm will receive a placebo treatment.	Other: Placebo; 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline [14 days]

   Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.

2. Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline [baseline and 14 days]

   Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Secondary Outcome Measures

1. Rate of Hospitalization [14 days]

   Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

2. Rate of Death [Approximately 30 days]

   Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.

3. Rate of Confirmed SARS-CoV-2 Detection [14 days]

   Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.

4. Occurrence of Symptoms Compatible With COVID-19 (Possible Disease) [14 days]

   Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.

5. Rate of All-Cause Study Medicine Discontinuation or Withdrawal [14 days]

   Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.

6. Overall Symptom Severity at 5 and 14 Days [5 and 14 days]

   Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

7. Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry [14 days]

   Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the number of participants who report a score of 3.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent

• Exposure to a COVID19 case within 4 days as either a household contact or occupational exposure, OR

• Symptomatic COVID19 case with confirmed diagnosis within 4 days of symptom onset OR symptomatic high risk exposure with known COVID19 contact and within 4 days of symptom onset;

Exclusion Criteria:

• Current hospitalization

• Allergy to hydroxychloroquine

• Retinal eye disease

• Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency

• Known chronic kidney disease, stage 4 or 5 or receiving dialysis

• Structural or ischemic heart disease

• Personal or Family History of Prolonged QT syndrome

• Weight < 50 kg

• Known Porphyria

• Current use of: hydroxychloroquine or cardiac medicines of: flecainide, Tambocor; amiodarone, Cordarone, Pacerone; digoxin or Digox, Digitek, Lanoxin; procainamide or Procan, Procanbid, propafenone, Rythmal, sotalol;

• Current use of medicines which prolong the QT interval including:

• Antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, itraconazole, or mefloquine

• Antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, wellbutrin, or venlafaxine

• Antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone

• Methadone

• Sumatriptan, zolmitriptan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nationwide Enrollment via Internet, please email: [e-mail]	Minneapolis	Minnesota	United States	55455
2	University of Minnesota	Minneapolis	Minnesota	United States	55455
3	University of Alberta	Edmonton	Alberta	Canada
4	University of Manitoba	Winnipeg	Manitoba	Canada
5	Research Institute of the McGill University Heath Centre	Montréal	Quebec	Canada

Sponsors and Collaborators

• University of Minnesota
• McGill University Health Centre/Research Institute of the McGill University Health Centre
• University of Manitoba
• University of Alberta

Investigators

• Principal Investigator: David Boulware, MD, MPH, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 24, 2020
• Informed Consent Form - Apr 24, 2020

More Information

Publications

• Al-Kofahi M, Jacobson P, Boulware DR, Matas A, Kandaswamy R, Jaber MM, Rajasingham R, Young JH, Nicol MR. Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness. Clin Pharmacol Ther. 2020 Oct;108(4):766-769. doi: 10.1002/cpt.1874. Epub 2020 Jun 1.
• Ingraham NE, Boulware D, Sparks MA, Schacker T, Benson B, Sparks JA, Murray T, Connett J, Chipman JG, Charles A, Tignanelli CJ. Shining a light on the evidence for hydroxychloroquine in SARS-CoV-2. Crit Care. 2020 Apr 28;24(1):182. doi: 10.1186/s13054-020-02894-7.
• Lother SA, Abassi M, Agostinis A, Bangdiwala AS, Cheng MP, Drobot G, Engen N, Hullsiek KH, Kelly LE, Lee TC, Lofgren SM, MacKenzie LJ, Marten N, McDonald EG, Okafor EC, Pastick KA, Pullen MF, Rajasingham R, Schwartz I, Skipper CP, Turgeon AF, Zarychanski R, Boulware DR. Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial. Can J Anaesth. 2020 Sep;67(9):1201-1211. doi: 10.1007/s12630-020-01684-7. Epub 2020 May 7.
• Okafor EC, Pastick KA, Rajasingham R. Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. Reply. N Engl J Med. 2020 Sep 10;383(11):1089. doi: 10.1056/NEJMc2023617. Epub 2020 Jul 15.
• Pastick KA, Okafor EC, Wang F, Lofgren SM, Skipper CP, Nicol MR, Pullen MF, Rajasingham R, McDonald EG, Lee TC, Schwartz IS, Kelly LE, Lother SA, Mitjà O, Letang E, Abassi M, Boulware DR. Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020 Apr 15;7(4):ofaa130. doi: 10.1093/ofid/ofaa130. eCollection 2020 Apr. Review.
• Pullen MF, Pastick KA, Williams DA, Nascene AA, Bangdiwala AS, Okafor EC, Hullsiek KH, Skipper CP, Lofgren SM, Engen N, Abassi M, McDonald EG, Lee TC, Rajasingham R, Boulware DR. Lessons Learned From Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic. Open Forum Infect Dis. 2020 Dec 28;8(2):ofaa602. doi: 10.1093/ofid/ofaa602. eCollection 2021 Feb. Review.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04308668
• Other Study ID Numbers: MED-2020-28673
• First Posted: Mar 16, 2020
• Last Update Posted: May 13, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Minnesota: COVID-19; Corona Virus; SARS-COV-2; Coronavirus
• Additional relevant MeSH terms: Infections; Communicable Diseases; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Hydroxychloroquine

Study Results

Participant Flow

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Period Title: Overall Study
STARTED	658	654
COMPLETED	622	612
NOT COMPLETED	36	42

Baseline Characteristics

Arm/Group Title	Treatment	Placebo	Total
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days	Total of all reporting groups
Overall Participants	658	654	1312
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (12)	42 (12)	42 (12)
Sex: Female, Male (Count of Participants)
Female	354 53.8%	336 51.4%	690 52.6%
Male	300 45.6%	314 48%	614 46.8%
Female	2 0.3%	2 0.3%	4 0.3%
Male	2 0.3%	2 0.3%	4 0.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	4 0.6%	2 0.3%	6 0.5%
Asian/South Asian	204 31%	206 31.5%	410 31.3%
Native Hawaiian or Pacific Islander	5 0.8%	4 0.6%	9 0.7%
Black or African American	28 4.3%	24 3.7%	52 4%
White	363 55.2%	379 58%	742 56.6%
Hispanic or Latino	37 5.6%	36 5.5%	73 5.6%
Middle Eastern	14 2.1%	9 1.4%	23 1.8%
Unknown/Not Reported	12 1.8%	10 1.5%	22 1.7%
Region of Enrollment (Count of Participants)
Canada	30 4.6%	29 4.4%	59 4.5%
United States	628 95.4%	625 95.6%	1253 95.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline
Description	Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	414	407
Count of Participants [Participants]	49 7.4%	58 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -7.0 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values represent percentages. Experimental treatment arm compared with the placebo control arm.

2. Primary Outcome

Title	Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline
Description	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time Frame	baseline and 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	212	211
Mean (Standard Error) [score on a scale]	-2.6 (.12)	-2.33 (.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.117
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.61 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Rate of Hospitalization
Description	Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	645	641
Count of Participants [Participants]	5 0.8%	9 1.4%

4. Secondary Outcome

Title	Rate of Death
Description	Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.
Time Frame	Approximately 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	645	641
Count of Participants [Participants]	1 0.2%	1 0.2%

5. Secondary Outcome

Title	Rate of Confirmed SARS-CoV-2 Detection
Description	Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	414	407
Count of Participants [Participants]	11 1.7%	9 1.4%

6. Secondary Outcome

Title	Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)
Description	Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	414	407
Count of Participants [Participants]	48 7.3%	55 8.4%

7. Secondary Outcome

Title	Rate of All-Cause Study Medicine Discontinuation or Withdrawal
Description	Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	645	641
Count of Participants [Participants]	97 14.7%	63 9.6%

8. Secondary Outcome

Title	Overall Symptom Severity at 5 and 14 Days
Description	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time Frame	5 and 14 days

Outcome Measure Data

Analysis Population Description

Early preemptive treatment trial (n=423 symptomatic participants with data)

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	212	211
Day 5	-2.22	-2.05
Day 14	-3.36	-3.08

9. Secondary Outcome

Title	Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry
Description	Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the number of participants who report a score of 3.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment	Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days	Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
Measure Participants	231	234
Count of Participants [Participants]	5 0.8%	8 1.2%

Adverse Events

Time Frame	Approximately 30-days
Adverse Event Reporting Description	Reporting period was for onset of adverse events within 14 days. All hospitalizations were followed for up to 90 days for final resolution of outcome. Approximately 30 days was the maximal duration needed to capture final outcome.
Arm/Group Title	Treatment		Placebo
Arm/Group Description	Participants in this arm will receive the study drug. Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days		Participants in this arm will receive a placebo treatment. Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
All Cause Mortality
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/658 (0.2%)		1/654 (0.2%)
Serious Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/658 (0.9%)		11/654 (1.7%)
Cardiac disorders
Hospitalizations not related to COVID or study medicine	0/658 (0%)	0	2/654 (0.3%)	2
Infections and infestations
COVID-related hospitalization	6/658 (0.9%)	6	9/654 (1.4%)	9
Other (Not Including Serious) Adverse Events
	Treatment		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	367/658 (55.8%)		148/654 (22.6%)
Ear and labyrinth disorders
Tinnitus	16/658 (2.4%)	16	8/654 (1.2%)	8
Eye disorders
Visual changes	7/658 (1.1%)	7	5/654 (0.8%)	5
Gastrointestinal disorders
Nausea or upset stomach	146/658 (22.2%)	146	53/654 (8.1%)	53
Diarrhea, abdominal pain, vomiting	131/658 (19.9%)	131	35/654 (5.4%)	35
General disorders
Irritability, dizziness, vertigo	39/658 (5.9%)	39	26/654 (4%)	26
Headache	15/658 (2.3%)	15	8/654 (1.2%)	8
Taste change or dry mouth	3/658 (0.5%)	3	3/654 (0.5%)	3
Hot flashes, night sweats, palpitations	2/658 (0.3%)	2	1/654 (0.2%)	1
Fatigue	1/658 (0.2%)	1	1/654 (0.2%)	1
Other	1/658 (0.2%)	1	2/654 (0.3%)	2
Immune system disorders
Allergic reaction (non-anaphylaxis)	6/658 (0.9%)	6	1/654 (0.2%)	1
Psychiatric disorders
Panic	0/658 (0%)	0	1/654 (0.2%)	1
Skin and subcutaneous tissue disorders
Skin reaction	10/658 (1.5%)	10	4/654 (0.6%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.