Trial Outcomes & Findings for Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (NCT NCT04332991)

NCT ID: NCT04332991

Last Updated: 2021-03-17

Results Overview

We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 479 participants
• Primary outcome timeframe: Assessed on study day 15
• Results posted on: 2021-03-17

Participant Flow

Participant milestones

Measure	Hydroxychloroquine 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.	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. 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 Study STARTED	242	237
Overall Study COMPLETED	242	237
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

This measure was analyzed in participants with available data on race and ethnicity.

Baseline characteristics by cohort

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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 n=479 Participants Total of all reporting groups
Age, Continuous	58 years n=242 Participants	57 years n=237 Participants	57 years n=479 Participants
Sex: Female, Male Female	107 Participants n=242 Participants	105 Participants n=237 Participants	212 Participants n=479 Participants
Sex: Female, Male Male	135 Participants n=242 Participants	132 Participants n=237 Participants	267 Participants n=479 Participants
Race/Ethnicity, Customized Non-Hispanic White	72 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	65 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	137 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized Non-Hispanic Black	57 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	55 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	112 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized Hispanic	91 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	87 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	178 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized Asian	4 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	7 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	11 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	2 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	4 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	6 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized Multi-race	1 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	1 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	2 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Race/Ethnicity, Customized American Indian or Alaska Native	5 Participants n=232 Participants • This measure was analyzed in participants with available data on race and ethnicity.	8 Participants n=227 Participants • This measure was analyzed in participants with available data on race and ethnicity.	13 Participants n=459 Participants • This measure was analyzed in participants with available data on race and ethnicity.
Living at home in the community prior to hospitalization	190 Participants n=242 Participants	183 Participants n=237 Participants	373 Participants n=479 Participants
Body mass index	31.3 kg/m^2 n=226 Participants • This measure was analyzed in participants with available data on body mass index	31.1 kg/m^2 n=219 Participants • This measure was analyzed in participants with available data on body mass index	31.1 kg/m^2 n=445 Participants • This measure was analyzed in participants with available data on body mass index
Chronic Conditions Hypertension	136 Participants n=242 Participants	117 Participants n=237 Participants	253 Participants n=479 Participants
Chronic Conditions Diabetes	88 Participants n=242 Participants	78 Participants n=237 Participants	166 Participants n=479 Participants
Chronic Conditions Chronic kidney disease	28 Participants n=242 Participants	14 Participants n=237 Participants	42 Participants n=479 Participants
Chronic Conditions Chronic artery disease	19 Participants n=242 Participants	23 Participants n=237 Participants	42 Participants n=479 Participants
Chronic Conditions Chronic obstructive pulmonary disease	18 Participants n=242 Participants	21 Participants n=237 Participants	39 Participants n=479 Participants
Location at time of randomization Hospital ward	157 Participants n=228 Participants • Measure was analyzed in participants with available data on location at time of randomization.	132 Participants n=224 Participants • Measure was analyzed in participants with available data on location at time of randomization.	289 Participants n=452 Participants • Measure was analyzed in participants with available data on location at time of randomization.
Location at time of randomization Intensive care unit	37 Participants n=228 Participants • Measure was analyzed in participants with available data on location at time of randomization.	54 Participants n=224 Participants • Measure was analyzed in participants with available data on location at time of randomization.	91 Participants n=452 Participants • Measure was analyzed in participants with available data on location at time of randomization.
Location at time of randomization Emergency department	34 Participants n=228 Participants • Measure was analyzed in participants with available data on location at time of randomization.	38 Participants n=224 Participants • Measure was analyzed in participants with available data on location at time of randomization.	72 Participants n=452 Participants • Measure was analyzed in participants with available data on location at time of randomization.
Symptoms of acute respiratory infection Shortness of breath	175 Participants n=242 Participants	168 Participants n=237 Participants	343 Participants n=479 Participants
Symptoms of acute respiratory infection Cough	143 Participants n=242 Participants	140 Participants n=237 Participants	283 Participants n=479 Participants
Symptoms of acute respiratory infection Fever (temperature > 37.5 degrees celsius)	138 Participants n=242 Participants	132 Participants n=237 Participants	270 Participants n=479 Participants
Duration of symptoms prior to randomization	5 days n=242 Participants	5 days n=237 Participants	5 days n=479 Participants
Time between hospital presentation and randomization	22.2 hours n=240 Participants • Measure was analyzed in participants who had available data for date of hospital presentation.	22.7 hours n=234 Participants • Measure was analyzed in participants who had available data for date of hospital presentation.	22.5 hours n=474 Participants • Measure was analyzed in participants who had available data for date of hospital presentation.
Aspartate aminotransferase	39 U/L n=173 Participants • Measure is analyzed in participants with available data on aspartate aminotransferase.	45 U/L n=184 Participants • Measure is analyzed in participants with available data on aspartate aminotransferase.	41 U/L n=357 Participants • Measure is analyzed in participants with available data on aspartate aminotransferase.
Alanine aminotransferase	30 U/L n=174 Participants • Measure was analyzed in participants with available data on alanine aminotransferase.	34 U/L n=183 Participants • Measure was analyzed in participants with available data on alanine aminotransferase.	31 U/L n=357 Participants • Measure was analyzed in participants with available data on alanine aminotransferase.
Bilateral infiltrates on chest imaging	147 Participants n=230 Participants • This measure was analyzed in participants with available data on bilateral infiltrates on chest imaging.	145 Participants n=230 Participants • This measure was analyzed in participants with available data on bilateral infiltrates on chest imaging.	292 Participants n=460 Participants • This measure was analyzed in participants with available data on bilateral infiltrates on chest imaging.
QTc interval	430 milliseconds n=242 Participants • This measure was analyzed in participants with available data on QTc interval.	435 milliseconds n=236 Participants • This measure was analyzed in participants with available data on QTc interval.	433 milliseconds n=478 Participants • This measure was analyzed in participants with available data on QTc interval.
COVID outcomes scale category at randomization 5: Hospitalized, not receiving supplemental oxygen	85 Participants n=242 Participants	83 Participants n=237 Participants	168 Participants n=479 Participants
Vasopressor use at enrollment	8 Participants n=242 Participants	20 Participants n=237 Participants	28 Participants n=479 Participants
Total SOFA score at enrollment	2 score n=242 Participants	2 score n=237 Participants	2 score n=479 Participants
White blood cell count	6.0 cells ×10^3/μL n=224 Participants • Measure is analyzed in participants with available data on white blood cell count.	5.9 cells ×10^3/μL n=218 Participants • Measure is analyzed in participants with available data on white blood cell count.	5.9 cells ×10^3/μL n=442 Participants • Measure is analyzed in participants with available data on white blood cell count.
Platelet count	199 cells ×10^3/μL n=237 Participants • Measure is analyzed in participants with available data on platelet count.	200 cells ×10^3/μL n=230 Participants • Measure is analyzed in participants with available data on platelet count.	199 cells ×10^3/μL n=467 Participants • Measure is analyzed in participants with available data on platelet count.
Creatinine	0.95 mg/dL n=235 Participants • Measure was analyzed in participants with available data on creatinine.	0.90 mg/dL n=231 Participants • Measure was analyzed in participants with available data on creatinine.	0.91 mg/dL n=466 Participants • Measure was analyzed in participants with available data on creatinine.
COVID outcomes scale category at randomization 2: Hospitalized, receiving ECMO or invasive mechanical ventilation	13 Participants n=242 Participants	19 Participants n=237 Participants	32 Participants n=479 Participants
COVID outcomes scale category at randomization 3: Hospitalized, receiving noninvasive ventilation or nasal high flow oxygen	28 Participants n=242 Participants	27 Participants n=237 Participants	55 Participants n=479 Participants
COVID outcomes scale category at randomization 4: Hospitalized, receiving supplemental oxygen without positive pressure or high flow	116 Participants n=242 Participants	108 Participants n=237 Participants	224 Participants n=479 Participants

PRIMARY outcome

Timeframe: Assessed on study day 15

We will determine the COVID Ordinal Scale for all patients on study day 15

COVID Ordinal Scale defined as:

1. Death

2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)

3. Hospitalized on non-invasive ventilation or high flow nasal cannula

4. Hospitalized on supplemental oxygen

5. Hospitalized not on supplemental oxygen

6. Not hospitalized with limitation in activity (continued symptoms)

7. Not hospitalized without limitation in activity (no symptoms)

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
COVID Outcomes Scale Score on Study Day 15 (14 Days After Randomization)	6 score on a scale Interval 4.0 to 7.0	6 score on a scale Interval 4.0 to 7.0

SECONDARY outcome

Timeframe: assessed on study day 3

We will determine the COVID Ordinal Scale for all patients on study day 3

COVID Ordinal Scale defined as:

1. Death

2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)

3. Hospitalized on non-invasive ventilation or high flow nasal cannula

4. Hospitalized on supplemental oxygen

5. Hospitalized not on supplemental oxygen

6. Not hospitalized with limitation in activity (continued symptoms)

7. Not hospitalized without limitation in activity (no symptoms)

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
COVID Ordinal Outcomes Scale on Study Day 3 (2 Days After Randomization)	4 score on a scale Interval 3.0 to 5.0	4 score on a scale Interval 3.0 to 5.0

SECONDARY outcome

Timeframe: assessed on study day 8

We will determine the COVID Ordinal Scale on study day 8

COVID Ordinal Scale defined as:

1. Death

2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)

3. Hospitalized on non-invasive ventilation or high flow nasal cannula

4. Hospitalized on supplemental oxygen

5. Hospitalized not on supplemental oxygen

6. Not hospitalized with limitation in activity (continued symptoms)

7. Not hospitalized without limitation in activity (no symptoms)

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
COVID Ordinal Outcomes Scale on Study Day 8 (7 Days After Randomization)	5 score on a scale Interval 4.0 to 7.0	6 score on a scale Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: assessed on study day 29

We will determine the COVID Ordinal Scale on study day 29

COVID Ordinal Scale defined as:

1. Death

2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)

3. Hospitalized on non-invasive ventilation or high flow nasal cannula

4. Hospitalized on supplemental oxygen

5. Hospitalized not on supplemental oxygen

6. Not hospitalized with limitation in activity (continued symptoms)

7. Not hospitalized without limitation in activity (no symptoms)

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
COVID Ordinal Outcomes Scale on Study Day 29 (28 Days After Randomization)	6 score on a scale Interval 6.0 to 7.0	6 score on a scale Interval 6.0 to 7.0

SECONDARY outcome

Timeframe: assessed on study day 15

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=241 Participants 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.	Placebo n=236 Participants 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-location, All-cause Mortality Assessed on Study Day 15 (14 Days After Randomization)	18 Participants	14 Participants

SECONDARY outcome

Timeframe: assessed on study day 29

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=241 Participants 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.	Placebo n=236 Participants 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-location, All-cause Mortality Assessed on Study Day 29 (28 Days After Randomization)	25 Participants	25 Participants

SECONDARY outcome

Timeframe: Enrollment to Day 28

Population: 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.

We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28

Outcome measures

Measure	Hydroxychloroquine n=241 Participants 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.	Placebo n=236 Participants 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.
Number of Patients Dead or With Receipt of ECMO Between Enrollment and Day 28	29 Participants	28 Participants

SECONDARY outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Oxygen-free Days Through Day 28	21 days Interval 0.0 to 27.0	20 days Interval 0.0 to 27.0

SECONDARY outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Ventilator-free Days Through Day 28	28 days Interval 28.0 to 28.0	28 days Interval 28.0 to 28.0

SECONDARY outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Vasopressor-free Days Through Day 28	28 days Interval 28.0 to 28.0	28 days Interval 28.0 to 28.0

SECONDARY outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
ICU-free Days to Day 28	28 days Interval 21.0 to 28.0	28 days Interval 18.0 to 28.0

SECONDARY outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Hospital-free Days to Day 28	21 days Interval 11.0 to 24.0	20 days Interval 10.0 to 24.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience seizure between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Seizures to Day 28	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience atrial arrhythmia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Atrial Arrhythmia to Day 28	15 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Ventricular Arrhythmia to Day 28	5 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience cardiac arrest between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Cardiac Arrest to Day 28	10 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

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

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Elevation in Aspartate Aminotransferase or Alanine Aminotransferase to Twice the Local Upper Limit of Normal to Day 28	50 Participants	65 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience acute pancreatitis between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Acute Pancreatitis Arrest to Day 28	5 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience acute kidney injury between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Acute Kidney Injury to day28	37 Participants	37 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience renal replacement therapy between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Receipt of Renal Replacement Therapy to Day 28	10 Participants	14 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Symptomatic Hypoglycemia to Day 28	10 Participants	8 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience neutropenia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Neutropenia to Day 28	4 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience lymphopenia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Lymphopenia to Day 28	92 Participants	87 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience anemia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Anemia to Day 28	139 Participants	120 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience thrombocytopenia between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Thrombocytopenia to Day 28	4 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
Number of Patients With Severe Dermatologic Reaction to Day 28	1 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after randomization

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.

Outcome measures

Measure	Hydroxychloroquine n=242 Participants 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.	Placebo n=237 Participants 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.
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	5 days Interval 1.0 to 14.0	6 days Interval 1.0 to 15.0

Adverse Events

Hydroxychlorquine

Serious events: 14 serious events

Other events: 30 other events

Deaths: 25 deaths

Placebo

Serious events: 11 serious events

Other events: 21 other events

Deaths: 25 deaths

Serious adverse events

Measure	Hydroxychlorquine n=242 participants at risk 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.	Placebo n=237 participants at risk 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.
Cardiac disorders Cardiac Arrest	0.00% 0/242 • 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.	0.84% 2/237 • Number of events 2 • 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.
Cardiac disorders Myocardial Infarction	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Cardiac disorders Ventricular Tachycardia	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Abdominal Distension	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Bleeding Gastrointestinal	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Gastrointestinal disorders Gall stones	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Nausea, Vomiting, Hematemesis	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Gastrointestinal disorders Obstruction Bowel	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
General disorders Death	0.83% 2/242 • Number of events 2 • 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.	0.00% 0/237 • 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.
Investigations Hypokalemia	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Investigations Reaction Nonspecific	0.41% 1/242 • Number of events 1 • 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.	0.42% 1/237 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Hematoma Muscle	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Musculoskeletal and connective tissue disorders Joint Pain	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Nervous system disorders Edema Cerebral	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Nervous system disorders Encephalopathy	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Nervous system disorders Headache	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Nervous system disorders Intracranial hemorrhage	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Nervous system disorders Stroke	0.41% 1/242 • Number of events 1 • 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.	0.84% 2/237 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.83% 2/242 • Number of events 2 • 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.	0.00% 0/237 • 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.83% 2/242 • Number of events 2 • 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.	0.00% 0/237 • 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.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Vascular disorders Hemorrhage Retroperitoneal	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.

Other adverse events

Measure	Hydroxychlorquine n=242 participants at risk 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.	Placebo n=237 participants at risk 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.
Blood and lymphatic system disorders Leukocytosis	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Cardiac disorders Atrial Arrythmia	0.41% 1/242 • Number of events 1 • 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.	0.84% 2/237 • Number of events 2 • 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.
Cardiac disorders Bradycardia	0.00% 0/242 • 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.	0.84% 2/237 • Number of events 2 • 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.
Cardiac disorders Cardiac Arrhythmia	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Cardiac disorders Cardiomyopathy	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Cardiac disorders Chest Pain	0.83% 2/242 • Number of events 2 • 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.	0.00% 0/237 • 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.
Cardiac disorders Conduction Disorder	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Cardiac disorders EKG Abnormality: Non-Specific	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Cardiac disorders Premature Ventricular Contractions	0.41% 1/242 • Number of events 1 • 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.	0.42% 1/237 • Number of events 1 • 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.
Cardiac disorders Prolonged QTc	0.83% 2/242 • Number of events 2 • 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.	1.3% 3/237 • Number of events 3 • 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.
Cardiac disorders Sinus Bradycardia	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Endocrine disorders Hypoglycemia	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Diarrhea	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Nausea	0.83% 2/242 • Number of events 2 • 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.	0.42% 1/237 • Number of events 1 • 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.
Gastrointestinal disorders Nausea, Vomiting	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Gastrointestinal disorders Nausea, Diarrhea	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
General disorders Contrast Extravasation	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Immune system disorders Allergic Reaction	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Investigations ALT Increased	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Investigations AST Increased	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Investigations Multiple Liver Function Tests Abnormal	4.1% 10/242 • Number of events 10 • 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.	1.3% 3/237 • Number of events 3 • 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.
Nervous system disorders Headache	1.2% 3/242 • Number of events 3 • 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.	0.84% 2/237 • Number of events 2 • 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.
Nervous system disorders Neuropathy Peripheral	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Renal and urinary disorders Kidney Function Abnormal	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.41% 1/242 • Number of events 1 • 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.	0.42% 1/237 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Itching	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Rash	0.41% 1/242 • Number of events 1 • 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.	0.42% 1/237 • Number of events 1 • 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.
Vascular disorders Flushing	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.
Vascular disorders Vagal Reaction	0.41% 1/242 • Number of events 1 • 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.	0.00% 0/237 • 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.
Vascular disorders Nosebleed	0.00% 0/242 • 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.	0.42% 1/237 • Number of events 1 • 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.

Additional Information

B.Taylor Thompson, MD

Mass General Hopsital (PETAL Network Coordinating Center)

Phone: 617-726-8854

Email: TTHOMPSON1@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place