Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID)

• ClinicalTrials.gov Identifier: NCT04332991
• Recruitment Status: Completed
• First Posted: April 3, 2020
• Results First Posted: March 17, 2021
• Last Update Posted: March 17, 2021
• Sponsor: Massachusetts General Hospital
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Boyd Taylor Thompson, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Coronavirus; Acute Respiratory Infection; SARS-CoV Infection
• Interventions: Drug: Hydroxychloroquine; Drug: Placebo
• Enrollment: 479

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Period Title: Overall Study
Started	242	237
Completed	242	237
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Hydroxychloroquine	Placebo	Total
Arm/Group Description		Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.	Total of all reporting groups
Overall Number of Baseline Participants		242	237	479
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	242 participants	237 participants	479 participants
		58; (45 to 69)	57; (43 to 68)	57; (44 to 68)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
	Female	107 44.2%	105 44.3%	212 44.3%
	Male	135 55.8%	132 55.7%	267 55.7%
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Non-Hispanic White	Number Analyzed	232 participants	227 participants	459 participants
		72 31.0%	65 28.6%	137 29.8%
Non-Hispanic Black	Number Analyzed	232 participants	227 participants	459 participants
		57 24.6%	55 24.2%	112 24.4%
Hispanic	Number Analyzed	232 participants	227 participants	459 participants
		91 39.2%	87 38.3%	178 38.8%
Asian	Number Analyzed	232 participants	227 participants	459 participants
		4 1.7%	7 3.1%	11 2.4%
Native Hawaiian or other Pacific Islander	Number Analyzed	232 participants	227 participants	459 participants
		2 0.9%	4 1.8%	6 1.3%
Multi-race	Number Analyzed	232 participants	227 participants	459 participants
		1 0.4%	1 0.4%	2 0.4%
American Indian or Alaska Native	Number Analyzed	232 participants	227 participants	459 participants
		5 2.2%	8 3.5%	13 2.8%
		[1] Measure Analysis Population Description: This measure was analyzed in participants with available data on race and ethnicity.
Living at home in the community prior to hospitalization; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
		190 78.5%	183 77.2%	373 77.9%
Body mass index [1]; Median (Inter-Quartile Range); Unit of measure: Kg/m^2
	Number Analyzed	226 participants	219 participants	445 participants
		31.3; (26.4 to 37.2)	31.1; (27.2 to 36.5)	31.1; (26.9 to 36.9)
		[1] Measure Analysis Population Description: This measure was analyzed in participants with available data on body mass index
Chronic Conditions; Measure Type: Count of Participants; Unit of measure: Participants
Hypertension	Number Analyzed	242 participants	237 participants	479 participants
		136 56.2%	117 49.4%	253 52.8%
Diabetes	Number Analyzed	242 participants	237 participants	479 participants
		88 36.4%	78 32.9%	166 34.7%
Chronic kidney disease	Number Analyzed	242 participants	237 participants	479 participants
		28 11.6%	14 5.9%	42 8.8%
Chronic artery disease	Number Analyzed	242 participants	237 participants	479 participants
		19 7.9%	23 9.7%	42 8.8%
Chronic obstructive pulmonary disease	Number Analyzed	242 participants	237 participants	479 participants
		18 7.4%	21 8.9%	39 8.1%
Location at time of randomization [1]; Measure Type: Count of Participants; Unit of measure: Participants
Hospital ward	Number Analyzed	228 participants	224 participants	452 participants
		157 68.9%	132 58.9%	289 63.9%
Intensive care unit	Number Analyzed	228 participants	224 participants	452 participants
		37 16.2%	54 24.1%	91 20.1%
Emergency department	Number Analyzed	228 participants	224 participants	452 participants
		34 14.9%	38 17.0%	72 15.9%
		[1] Measure Analysis Population Description: Measure was analyzed in participants with available data on location at time of randomization.
Symptoms of acute respiratory infection; Measure Type: Count of Participants; Unit of measure: Participants
Shortness of breath	Number Analyzed	242 participants	237 participants	479 participants
		175 72.3%	168 70.9%	343 71.6%
Cough	Number Analyzed	242 participants	237 participants	479 participants
		143 59.1%	140 59.1%	283 59.1%
Fever (temperature > 37.5 degrees celsius)	Number Analyzed	242 participants	237 participants	479 participants
		138 57.0%	132 55.7%	270 56.4%
Duration of symptoms prior to randomization; Median (Inter-Quartile Range); Unit of measure: Days
	Number Analyzed	242 participants	237 participants	479 participants
		5; (3 to 7)	5; (3 to 7)	5; (3 to 7)
Time between hospital presentation and randomization [1] [2]; Median (Inter-Quartile Range); Unit of measure: Hours
	Number Analyzed	240 participants	234 participants	474 participants
		22.2; (14.6 to 33.1)	22.7; (14.1 to 29.9)	22.5; (14.3 to 31.6)
		[1] Measure Description: Defined as the time of the first contact with an acute care hospital during the health care episode that resulted in the hospitalization during which the patient was enrolled. For patients who initially presented to the emergency department, time of hospital presentation was the time of emergency department arrival. For patients directly hospitalized without presenting to the emergency department, time of hospital presentation was the time of arrival at the admission unit.; [2] Measure Analysis Population Description: Measure was analyzed in participants who had available data for date of hospital presentation.
COVID outcomes scale category at randomization [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
	2: Hospitalized, receiving ECMO or invasive mechanical ventilation	13 5.4%	19 8.0%	32 6.7%
	3: Hospitalized, receiving noninvasive ventilation or nasal high flow oxygen	28 11.6%	27 11.4%	55 11.5%
	4: Hospitalized, receiving supplemental oxygen without positive pressure or high flow	116 47.9%	108 45.6%	224 46.8%
	5: Hospitalized, not receiving supplemental oxygen	85 35.1%	83 35.0%	168 35.1%
		[1] Measure Description: The COVID Outcomes Scale is a 7-category ordinal scale that classifies a patient's clinical status. Lower scores indicate more severely ill clinical status. Patients in the following categories at baseline were not eligible for enrollment: category 1 (death); category 6 (not hospitalized and unable to perform normal activities); and category 7 (not hospitalized and able to perform normal activities).
Vasopressor use at enrollment; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
		8 3.3%	20 8.4%	28 5.8%
Total SOFA score at enrollment [1]; Median (Inter-Quartile Range); Unit of measure: Score
	Number Analyzed	242 participants	237 participants	479 participants
		2; (1 to 4)	2; (1 to 4)	2; (1 to 4)
		[1] Measure Description: The SOFA score categorizes illness severity based on organ dysfunction across 6 organ systems: respiratory, coagulation, liver, cardiovascular, central nervous system, and kidney. SOFA scores range from 0 to 24, with higher scores indicating greater illness severity. A SOFA score of 2 indicates moderate dysfunction in 1 organ system or mild dysfunction in 2 organ systems.
White blood cell count [1] [2]; Median (Inter-Quartile Range); Unit of measure: Cells ×10^3/μL
	Number Analyzed	224 participants	218 participants	442 participants
		6.0; (4.3 to 7.9)	5.9; (4.1 to 7.7)	5.9; (4.2 to 7.8)
		[1] Measure Description: Normal range for WBC: 3.9-10.7; [2] Measure Analysis Population Description: Measure is analyzed in participants with available data on white blood cell count.
Platelet count [1] [2]; Median (Inter-Quartile Range); Unit of measure: Cells ×10^3/μL
	Number Analyzed	237 participants	230 participants	467 participants
		199; (151 to 247)	200; (147 to 251)	199; (148 to 250)
		[1] Measure Description: Normal range for platelet: 135-371 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories.; [2] Measure Analysis Population Description: Measure is analyzed in participants with available data on platelet count.
Creatinine [1] [2]; Median (Inter-Quartile Range); Unit of measure: mg/dL
	Number Analyzed	235 participants	231 participants	466 participants
		0.95; (0.75 to 1.47)	0.90; (0.75 to 1.25)	0.91; (0.75 to 1.36)
		[1] Measure Description: Normal range for creatinine: 0.57-1.11 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories.; [2] Measure Analysis Population Description: Measure was analyzed in participants with available data on creatinine.
Aspartate aminotransferase [1] [2]; Median (Inter-Quartile Range); Unit of measure: U/L
	Number Analyzed	173 participants	184 participants	357 participants
		39; (29 to 62)	45; (31 to 70)	41; (29 to 66)
		[1] Measure Description: Normal range for aspartate aminotransferase: 5-40 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories.; [2] Measure Analysis Population Description: Measure is analyzed in participants with available data on aspartate aminotransferase.
Alanine aminotransferase [1] [2]; Median (Inter-Quartile Range); Unit of measure: U/L
	Number Analyzed	174 participants	183 participants	357 participants
		30; (18 to 47)	34; (23 to 62)	31; (20 to 56)
		[1] Measure Description: Normal range for alanine aminotransferase: 0-55 Laboratory normal ranges were reported base on the clinical laboratory normal ranges from Vanderbilt University Medical Center. Normal ranges may vary across laboratories.; [2] Measure Analysis Population Description: Measure was analyzed in participants with available data on alanine aminotransferase.
Bilateral infiltrates on chest imaging [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	230 participants	230 participants	460 participants
		147 63.9%	145 63.0%	292 63.5%
		[1] Measure Description: Reported chest imaging interpretations were based on final interpretation from radiologists.; [2] Measure Analysis Population Description: This measure was analyzed in participants with available data on bilateral infiltrates on chest imaging.
QTc interval [1] [2]; Median (Inter-Quartile Range); Unit of measure: Milliseconds
	Number Analyzed	242 participants	236 participants	478 participants
		430; (414 to 452)	435; (416 to 452)	433; (415 to 452)
		[1] Measure Description: Reported QTc was based on automated readings.; [2] Measure Analysis Population Description: This measure was analyzed in participants with available data on QTc interval.

Outcome Measures

1. Primary Outcome

Title	COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization)
Description	We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)
Time Frame	Assessed on study day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	6; (4 to 7)	6; (4 to 7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.42
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group.

2. Secondary Outcome

Title	COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization)
Description	We will determine the COVID Ordinal Scale for all patients on study day 3 COVID Ordinal Scale defined as: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)
Time Frame	assessed on study day 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	4; (3 to 5)	4; (3 to 5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.81
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

3. Secondary Outcome

Title	COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization)
Description	We will determine the COVID Ordinal Scale on study day 8 COVID Ordinal Scale defined as: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)
Time Frame	assessed on study day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	5; (4 to 7)	6; (3 to 6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.61
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

4. Secondary Outcome

Title	COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization)
Description	We will determine the COVID Ordinal Scale on study day 29 COVID Ordinal Scale defined as: Death; Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation); Hospitalized on non-invasive ventilation or high flow nasal cannula; Hospitalized on supplemental oxygen; Hospitalized not on supplemental oxygen; Not hospitalized with limitation in activity (continued symptoms); Not hospitalized without limitation in activity (no symptoms)
Time Frame	assessed on study day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	6; (6 to 7)	6; (6 to 7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure is adjusted for : age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.38
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

5. Secondary Outcome

Title	All-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization)
Description	Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status.
Time Frame	assessed on study day 15

Outcome Measure Data

Analysis Population Description

Outcome was measured in participants with available data on vital status. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	241	236
Measure Type: Count of Participants; Unit of Measure: Participants
	18 7.5%	14 5.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95%; 0.68 to 3.57
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

6. Secondary Outcome

Title	All-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization)
Description	Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy. There were two patients for whom we were unable to collect their vital status.
Time Frame	assessed on study day 29

Outcome Measure Data

Analysis Population Description

Outcome was measured in participants with available data on vital status. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	241	236
Measure Type: Count of Participants; Unit of Measure: Participants
	25 10.4%	25 10.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.54 to 2.09
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

7. Secondary Outcome

Title	Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28
Description	We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Time Frame	Enrollment to Day 28

Outcome Measure Data

Analysis Population Description

Outcome was measured in participants with available data on vital status or ECMO. One patient in the hydroxychloroquine group and one patient in the placebo group were lost to follow-up for vital status.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	241	236
Measure Type: Count of Participants; Unit of Measure: Participants
	29 12.0%	28 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.60 to 2.14
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

8. Secondary Outcome

Title	Oxygen-free Days Through Day 28
Description	The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	21; (0 to 27)	20; (0 to 27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.68 to 1.34
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

9. Secondary Outcome

Title	Ventilator-free Days Through Day 28
Description	Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	28; (28 to 28)	28; (28 to 28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 0.76 to 2.08
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

10. Secondary Outcome

Title	Vasopressor-free Days Through Day 28
Description	The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	28; (28 to 28)	28; (28 to 28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.72
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

11. Secondary Outcome

Title	ICU-free Days to Day 28
Description	The number of days spent out of the ICU to day 28. Patients who die prior to day 28 are assigned zero ICU free days.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	28; (21 to 28)	28; (18 to 28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.88
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

12. Secondary Outcome

Title	Hospital-free Days to Day 28
Description	Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	21; (11 to 24)	20; (10 to 24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.61
	Estimation Comments	Odds ratios greater than 1.0 indicated more favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

13. Other Pre-specified Outcome

Title	Number of Patients With Seizures to Day 28
Description	We will determine the number of patients that experience seizure between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	1 0.4%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.8
	Estimation Comments	[Not Specified]

14. Other Pre-specified Outcome

Title	Number of Patients With Atrial Arrhythmia to Day 28
Description	We will determine the number of patients that experience atrial arrhythmia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	15 6.2%	11 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.61 to 3.02
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

15. Other Pre-specified Outcome

Title	Number of Patients With Ventricular Arrhythmia to Day 28
Description	We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	5 2.1%	6 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.24 to 2.70
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

16. Other Pre-specified Outcome

Title	Number of Patients With Cardiac Arrest to Day 28
Description	We will determine the number of patients that experience cardiac arrest between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	10 4.1%	4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.51
	Confidence Interval	(2-Sided) 95%; 0.78 to 8.12
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

17. Other Pre-specified Outcome

Title	Number of Patients With Elevation in Aspartate Aminotransferase or Alanine Aminotransferase to Twice the Local Upper Limit of Normal to Day 28
Description	We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	50 20.7%	65 27.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.05
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

18. Other Pre-specified Outcome

Title	Number of Patients With Acute Pancreatitis Arrest to Day 28
Description	We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	5 2.1%	6 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.24 to 2.70
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

19. Other Pre-specified Outcome

Title	Number of Patients With Acute Kidney Injury to day28
Description	We will determine the number of patients that experience acute kidney injury between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	37 15.3%	37 15.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.59
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

20. Other Pre-specified Outcome

Title	Number of Patients With Receipt of Renal Replacement Therapy to Day 28
Description	We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	10 4.1%	14 5.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.30 to 1.58
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

21. Other Pre-specified Outcome

Title	Number of Patients With Symptomatic Hypoglycemia to Day 28
Description	We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	10 4.1%	8 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.48 to 3.18
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

22. Other Pre-specified Outcome

Title	Number of Patients With Neutropenia to Day 28
Description	We will determine the number of patients that experience neutropenia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	4 1.7%	4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.24 to 3.96
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

23. Other Pre-specified Outcome

Title	Number of Patients With Lymphopenia to Day 28
Description	We will determine the number of patients that experience lymphopenia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	92 38.0%	87 36.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.53
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

24. Other Pre-specified Outcome

Title	Number of Patients With Anemia to Day 28
Description	We will determine the number of patients that experience anemia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	139 57.4%	120 50.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.89
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

25. Other Pre-specified Outcome

Title	Number of Patients With Thrombocytopenia to Day 28
Description	We will determine the number of patients that experience thrombocytopenia between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	4 1.7%	5 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.21 to 2.94
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

26. Other Pre-specified Outcome

Title	Number of Patients With Severe Dermatologic Reaction to Day 28
Description	We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants; Unit of Measure: Participants
	1 0.4%	1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.06 to 15.74
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

27. Other Pre-specified Outcome

Title	Time to Recovery, Defined as Time to Reaching Level 5, 6, or 7 on the COVID Outcomes Scale, Which is the Time to the Earlier of Final Liberation From Supplemental Oxygen or Hospital Discharge
Description	Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge. Patients who die prior to day 28 are assigned 28 days for time to recovery.
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/Group Description:	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.	Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
Overall Number of Participants Analyzed	242	237
Median (Inter-Quartile Range); Unit of Measure: days
	5; (1 to 14)	6; (1 to 15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxychloroquine, Placebo
	Comments	Outcome measure was adjusted for: age, sex, baseline COVID Outcome Scale category, baseline Sequential Organ Failure Assessment score, and duration of acute respiratory infection symptoms prior to randomization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.35
	Estimation Comments	Odds ratios greater than 1.0 indicated less favorable outcomes for patients in the hydroxychloroquine group compared with the placebo group

Adverse Events

Time Frame	Subjects were assessed for adverse events from enrollment through study day 29 or discharge, whichever occurs first. Investigators will determine if the event is serious or related to study drug.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Hydroxychlorquine		Placebo
Arm/Group Description	Participants assigned to the hydroxychloroquine arm will receive hydroxychloroquine sulfate 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course. Hydroxychloroquine: Hydroxychloroquine is available in 200 mg oral tablets of hydroxychloroquine sulfate. For this COVID-19 trial, we will use an oral or enteral dose of hydroxychloroquine 400 mg twice daily on the day of enrollment, then 200 mg twice daily for the next 4 days for a 5 day total course.		Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding. Placebo: Participants randomized to the control group will receive a dose of placebo enterally twice daily for 5 days (a total of 10 doses). The placebo pills will be as similar as possible to the hydroxychloroquine pills to ensure blinding.
All-Cause Mortality
	Hydroxychlorquine		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	25/242 (10.33%)		25/237 (10.55%)
Serious Adverse Events
	Hydroxychlorquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/242 (5.79%)		11/237 (4.64%)
Cardiac disorders
Cardiac Arrest * 1	0/242 (0.00%)	0	2/237 (0.84%)	2
Myocardial Infarction * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Ventricular Tachycardia * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Gastrointestinal disorders
Abdominal Distension * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Bleeding Gastrointestinal * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Gall stones * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Nausea, Vomiting, Hematemesis * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Obstruction Bowel * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
General disorders
Death * 1	2/242 (0.83%)	2	0/237 (0.00%)	0
Investigations
Hypokalemia * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Reaction Nonspecific * 1	1/242 (0.41%)	1	1/237 (0.42%)	1
Musculoskeletal and connective tissue disorders
Hematoma Muscle * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Joint Pain * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Nervous system disorders
Edema Cerebral * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Encephalopathy * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Headache * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Intracranial hemorrhage * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Stroke * 1	1/242 (0.41%)	1	2/237 (0.84%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia * 1	2/242 (0.83%)	2	0/237 (0.00%)	0
Pneumothorax * 1	2/242 (0.83%)	2	0/237 (0.00%)	0
Respiratory Distress * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Shortness of Breath * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Vascular disorders
Hemorrhage Retroperitoneal * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
1 Term from vocabulary, MedDRA (10.0); * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Hydroxychlorquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/242 (12.40%)		21/237 (8.86%)
Blood and lymphatic system disorders
Leukocytosis * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Cardiac disorders
Atrial Arrythmia * 1	1/242 (0.41%)	1	2/237 (0.84%)	2
Bradycardia * 1	0/242 (0.00%)	0	2/237 (0.84%)	2
Cardiac Arrhythmia * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Cardiomyopathy * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Chest Pain * 1	2/242 (0.83%)	2	0/237 (0.00%)	0
Conduction Disorder * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
EKG Abnormality: Non-Specific * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Premature Ventricular Contractions * 1	1/242 (0.41%)	1	1/237 (0.42%)	1
Prolonged QTc * 1	2/242 (0.83%)	2	3/237 (1.27%)	3
Sinus Bradycardia * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Endocrine disorders
Hypoglycemia * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Gastrointestinal disorders
Diarrhea * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Nausea * 1	2/242 (0.83%)	2	1/237 (0.42%)	1
Nausea, Vomiting * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Nausea, Diarrhea * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
General disorders
Contrast Extravasation * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Immune system disorders
Allergic Reaction * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Investigations
ALT Increased * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
AST Increased * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Multiple Liver Function Tests Abnormal * 1	10/242 (4.13%)	10	3/237 (1.27%)	3
Nervous system disorders
Headache * 1	3/242 (1.24%)	3	2/237 (0.84%)	2
Neuropathy Peripheral * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Renal and urinary disorders
Kidney Function Abnormal * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia * 1	1/242 (0.41%)	1	1/237 (0.42%)	1
Skin and subcutaneous tissue disorders
Itching * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Rash * 1	1/242 (0.41%)	1	1/237 (0.42%)	1
Vascular disorders
Flushing * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
Vagal Reaction * 1	1/242 (0.41%)	1	0/237 (0.00%)	0
Nosebleed * 1	0/242 (0.00%)	0	1/237 (0.42%)	1
1 Term from vocabulary, MedDRA (10.0); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: B.Taylor Thompson, MD
• Organization: Mass General Hopsital (PETAL Network Coordinating Center)
• Phone: 617-726-8854
• EMail: TTHOMPSON1@mgh.harvard.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Self WH, Semler MW, Leither LM, Casey JD, Angus DC, Brower RG, Chang SY, Collins SP, Eppensteiner JC, Filbin MR, Files DC, Gibbs KW, Ginde AA, Gong MN, Harrell FE Jr, Hayden DL, Hough CL, Johnson NJ, Khan A, Lindsell CJ, Matthay MA, Moss M, Park PK, Rice TW, Robinson BRH, Schoenfeld DA, Shapiro NI, Steingrub JS, Ulysse CA, Weissman A, Yealy DM, Thompson BT, Brown SM; National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Steingrub J, Smithline H, Tiru B, Tidswell M, Kozikowski L, Thornton-Thompson S, De Souza L, Hou P, Baron R, Massaro A, Aisiku I, Fredenburgh L, Seethala R, Johnsky L, Riker R, Seder D, May T, Baumann M, Eldridge A, Lord C, Shapiro N, Talmor D, O'Mara T, Kirk C, Harrison K, Kurt L, Schermerhorn M, Banner-Goodspeed V, Boyle K, Dubosh N, Filbin M, Hibbert K, Parry B, Lavin-Parsons K, Pulido N, Lilley B, Lodenstein C, Margolin J, Brait K, Jones A, Galbraith J, Peacock R, Nandi U, Wachs T, Matthay M, Liu K, Kangelaris K, Wang R, Calfee C, Yee K, Hendey G, Chang S, Lim G, Qadir N, Tam A, Beutler R, Levitt J, Wilson J, Rogers A, Vojnik R, Roque J, Albertson T, Chenoweth J, Adams J, Pearson S, Juarez M, Almasri E, Fayed M, Hughes A, Hillard S, Huebinger R, Wang H, Vidales E, Patel B, Ginde A, Moss M, Baduashvili A, McKeehan J, Finck L, Higgins C, Howell M, Douglas I, Haukoos J, Hiller T, Lyle C, Cupelo A, Caruso E, Camacho C, Gravitz S, Finigan J, Griesmer C, Park P, Hyzy R, Nelson K, McDonough K, Olbrich N, Williams M, Kapoor R, Nash J, Willig M, Ford H, Gardner-Gray J, Ramesh M, Moses M, Ng Gong M, Aboodi M, Asghar A, Amosu O, Torres M, Kaur S, Chen JT, Hope A, Lopez B, Rosales K, Young You J, Mosier J, Hypes C, Natt B, Borg B, Salvagio Campbell E, Hite RD, Hudock K, Cresie A, Alhasan F, Gomez-Arroyo J, Duggal A, Mehkri O, Hastings A, Sahoo D, Abi Fadel F, Gole S, Shaner V, Wimer A, Meli Y, King A, Terndrup T, Exline M, Pannu S, Robart E, Karow S, Hough C, Robinson B, Johnson N, Henning D, Campo M, Gundel S, Seghal S, Katsandres S, Dean S, Khan A, Krol O, Jouzestani M, Huynh P, Weissman A, Yealy D, Scholl D, Adams P, McVerry B, Huang D, Angus D, Schooler J, Moore S, Files C, Miller C, Gibbs K, LaRose M, Flores L, Koehler L, Morse C, Sanders J, Langford C, Nanney K, MdalaGausi M, Yeboah P, Morris P, Sturgill J, Seif S, Cassity E, Dhar S, de Wit M, Mason J, Goodwin A, Hall G, Grady A, Chamberlain A, Brown S, Bledsoe J, Leither L, Peltan I, Starr N, Fergus M, Aston V, Montgomery Q, Smith R, Merrill M, Brown K, Armbruster B, Harris E, Middleton E, Paine R, Johnson S, Barrios M, Eppensteiner J, Limkakeng A, McGowan L, Porter T, Bouffler A, Leahy JC, deBoisblanc B, Lammi M, Happel K, Lauto P, Self W, Casey J, Semler M, Collins S, Harrell F, Lindsell C, Rice T, Stubblefield W, Gray C, Johnson J, Roth M, Hays M, Torr D, Zakaria A, Schoenfeld D, Thompson T, Hayden D, Ringwood N, Oldmixon C, Ulysse C, Morse R, Muzikansky A, Fitzgerald L, Whitaker S, Lagakos A, Brower R, Reineck L, Aggarwal N, Bienstock K, Freemer M, Maclawiw M, Weinmann G, Morrison L, Gillespie M, Kryscio R, Brodie D, Zareba W, Rompalo A, Boeckh M, Parsons P, Christie J, Hall J, Horton N, Zoloth L, Dickert N, Diercks D. Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Dec 1;324(21):2165-2176. doi: 10.1001/jama.2020.22240.

Casey JD, Johnson NJ, Semler MW, Collins SP, Aggarwal NR, Brower RG, Chang SY, Eppensteiner J, Filbin M, Gibbs KW, Ginde AA, Gong MN, Harrell F, Hayden DL, Hough CL, Khan A, Leither LM, Moss M, Oldmixon CF, Park PK, Reineck LA, Ringwood NJ, Robinson BRH, Schoenfeld DA, Shapiro NI, Steingrub JS, Torr DK, Weissman A, Lindsell CJ, Rice TW, Thompson BT, Brown SM, Self WH. Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19. Ann Am Thorac Soc. 2020 Sep;17(9):1144-1153. doi: 10.1513/AnnalsATS.202005-478SD.

• Responsible Party: Boyd Taylor Thompson, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04332991
• Other Study ID Numbers: PETAL 05 Orchid
• First Submitted: March 31, 2020
• First Posted: April 3, 2020
• Results First Submitted: February 9, 2021
• Results First Posted: March 17, 2021
• Last Update Posted: March 17, 2021