Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04335552
• Collaborator: (none)
• Enrollment: 11
• Locations: 4
• Arms: 4
• Actual Duration (Months): 2.3
• Patients Per Site: 2.8
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens:

Arm 1: Standard of care alone

Arm 2: Standard of care plus hydroxychloroquine

Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups:

1. Standard of care alone

2. Standard of care plus hydroxychloroquine

3. Standard of care plus azithromycin

4. Standard of care plus hydroxychloroquine plus azithromycin

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2	Other: Standard of care; Drug: Hydroxychloroquine; Drug: Azithromycin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: Patients will be initially randomized to one of two arms in a 1:1 ratio: 1) Standard of care treatment or 2) Standard of care treatment plus 5 days of hydroxychloroquine. Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy.Patients will be initially randomized to one of two arms in a 1:1 ratio: 1) Standard of care treatment or 2) Standard of care treatment plus 5 days of hydroxychloroquine. Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
• Actual Study Start Date: Apr 17, 2020
• Actual Primary Completion Date: Jun 17, 2020
• Actual Study Completion Date: Jun 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of care	Other: Standard of care; Standard of care
Experimental: Standard of care plus hydroxychloroquine Standard of care plus hydroxychloroquine for 5 days	Other: Standard of care; Standard of care; Drug: Hydroxychloroquine; Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5
Experimental: Standard of care plus azithromycin Standard of care plus azithromycin for 5 days	Other: Standard of care; Standard of care; Drug: Azithromycin; Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Experimental: Standard of care plus hydroxychloroquine plus azithromycin Standard of care plus hydroxychloroquine plus azithromycin for 5 days	Other: Standard of care; Standard of care; Drug: Hydroxychloroquine; Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5; Drug: Azithromycin; Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5

Outcome Measures

Primary Outcome Measures

1. World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment [Day 14]

   The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Secondary Outcome Measures

1. Number of Participants Who Died During the Index Hospitalization [Index hospitalization, up to 46 days]

2. Number of Days on Mechanical Ventilation [Baseline]

3. Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization [Index hospitalization, up to 46 days]

4. WHO Ordinal Scale Measured at 28 Days After Enrollment [Day 28]

   The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

5. Hospital Length of Stay in Days for the Index Hospitalization [Index hospitalization, up to 46 days]

6. Number of Participants With All-cause Study Medication Discontinuation [Index hospitalization, up to 46 days]

   Number of participants who discontinued study medication for any reason

7. Number of Participants With Severe Adverse Events [Day 14]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR develop symptoms of COVID-19 during hospitalization

2. Subject (or legally authorized representative) can provide written informed consent (in English or Spanish) affirming intention to comply with planned study procedures prior to enrollment

3. Male or female adult aged 12 years or older at the time of enrollment

4. Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid amplification assay (public health or commercial) in any respiratory specimen collected within 14 days of randomization

5. Illness of any duration that includes

• Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR

• Clinical documentation of lower respiratory symptoms (cough, shortness of breath, wheezing) OR

• Any documented SpO2 ≤ 94% on room air OR

• Any inpatient initiation or supplemental oxygen regardless of documented cause

Exclusion Criteria:

1. Participating in any other clinical trial of an experimental agent for COVID-19

2. On hydroxychloroquine at any time during hospitalization, or within 180 days of hospitalization for COVID-19 regardless of indication

3. History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any classification

4. Most recent ECG prior to time of screening with QTc of ≥500 msec

5. Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives

6. Death anticipated within 48 hours of enrollment

7. Inability to obtain informed consent from the patient or designated medical decision maker

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Regional Hospital	Durham	North Carolina	United States	27704
2	Duke University Hospital	Durham	North Carolina	United States	27710
3	Durham VA Medical Center	Durham	North Carolina	United States	27710
4	Duke Raleigh Hospital	Raleigh	North Carolina	United States	27609

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Jason Stout, MD, Duke University Hospital

Study Documents (Full-Text)

• Study Protocol - Apr 7, 2020
• Statistical Analysis Plan - May 1, 2020
• Informed Consent Form - Apr 13, 2020

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT04335552
• Other Study ID Numbers: PRO00105339
• First Posted: Apr 6, 2020
• Last Update Posted: May 17, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Duke University: COVID-19
• Additional relevant MeSH terms: COVID-19; Azithromycin; Hydroxychloroquine

Study Results

Participant Flow

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Period Title: Overall Study
STARTED	2	4	3	2
COMPLETED	1	4	3	2
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin	Total
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Total of all reporting groups
Overall Participants	2	4	3	2	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (20.5)	59.0 (14.1)	57.0 (4.2)	50.3 (12.5)	54.7 (12.9)
Sex: Female, Male (Count of Participants)
Female	1 50%	1 25%	1 33.3%	0 0%	3 27.3%
Male	1 50%	3 75%	2 66.7%	2 100%	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 75%	2 66.7%	1 50%	6 54.5%
Not Hispanic or Latino	2 100%	1 25%	1 33.3%	1 50%	5 45.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 50%	0 0%	1 33.3%	1 50%	3 27.3%
White	1 50%	3 75%	2 66.7%	1 50%	7 63.6%
More than one race	0 0%	1 25%	0 0%	0 0%	1 9.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%	4 100%	3 100%	2 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Intention to treat (includes all randomized, excludes 1 participant who withdrew prior to outcome measurement)

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Mean (Standard Deviation) [units on a scale]	1 (NA)	2.5 (3)	5.3 (3.8)	4.5 (5.0)

2. Secondary Outcome

Title	Number of Participants Who Died During the Index Hospitalization
Time Frame	Index hospitalization, up to 46 days

Outcome Measure Data

Analysis Population Description

Intention to treat (1 participant who withdrew not included)

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Count of Participants [Participants]	0 0%	1 25%	2 66.7%	1 50%

3. Secondary Outcome

Title	Number of Days on Mechanical Ventilation
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intention to treat (1 participant who withdrew excluded)

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Mean (Standard Deviation) [days]	0 (NA)	5.5 (11)	8.67 (15)	0 (0)

4. Secondary Outcome

Title	Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization
Time Frame	Index hospitalization, up to 46 days

Outcome Measure Data

Analysis Population Description

Intention to treat excluding 1 participant who withdrew

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Count of Participants [Participants]	0 0%	1 25%	1 33.3%	0 0%

5. Secondary Outcome

Title	WHO Ordinal Scale Measured at 28 Days After Enrollment
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Intention to treat excluding 1 participant who withdrew

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Mean (Standard Deviation) [score on a scale]	1 (NA)	2.8 (3.5)	5.3 (3.8)	4.5 (5.0)

6. Secondary Outcome

Title	Hospital Length of Stay in Days for the Index Hospitalization
Time Frame	Index hospitalization, up to 46 days

Outcome Measure Data

Analysis Population Description

Intention to treat excluding 1 participant who withdrew

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Mean (Standard Deviation) [days]	6 (NA)	9 (11)	14.7 (14.6)	2.5 (0.7)

7. Secondary Outcome

Title	Number of Participants With All-cause Study Medication Discontinuation
Description	Number of participants who discontinued study medication for any reason
Time Frame	Index hospitalization, up to 46 days

Outcome Measure Data

Analysis Population Description

Intention to treat excluding 1 participant who withdrew

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Severe Adverse Events
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Intention to treat excluding 1 participant who withdrew

Arm/Group Title	Standard of Care	Standard of Care Plus Hydroxychloroquine	Standard of Care Plus Azithromycin	Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care	Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Measure Participants	1	4	3	2
Count of Participants [Participants]	0 0%	1 25%	1 33.3%	0 0%

Adverse Events

Time Frame	2 months
Arm/Group Title	Standard of Care		Standard of Care Plus Hydroxychloroquine		Standard of Care Plus Azithromycin		Standard of Care Plus Hydroxychloroquine Plus Azithromycin
Arm/Group Description	Standard of care: Standard of care		Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5		Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5		Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
All Cause Mortality
	Standard of Care		Standard of Care Plus Hydroxychloroquine		Standard of Care Plus Azithromycin		Standard of Care Plus Hydroxychloroquine Plus Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/4 (25%)		2/3 (66.7%)		1/2 (50%)
Serious Adverse Events
	Standard of Care		Standard of Care Plus Hydroxychloroquine		Standard of Care Plus Azithromycin		Standard of Care Plus Hydroxychloroquine Plus Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/4 (25%)		1/3 (33.3%)		0/2 (0%)
Renal and urinary disorders
Acute renal failure	0/1 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/1 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Standard of Care		Standard of Care Plus Hydroxychloroquine		Standard of Care Plus Azithromycin		Standard of Care Plus Hydroxychloroquine Plus Azithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/4 (0%)		0/3 (0%)		0/2 (0%)

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.