Trial Outcomes & Findings for Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection (NCT NCT04335552)

NCT ID: NCT04335552

Last Updated: 2021-05-17

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 11 participants
• Primary outcome timeframe: Day 14
• Results posted on: 2021-05-17

Participant Flow

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Standard of Care n=2 Participants Standard of care: Standard of care	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Total n=11 Participants Total of all reporting groups
Age, Continuous	56.3 years STANDARD_DEVIATION 20.5 • n=5 Participants	59.0 years STANDARD_DEVIATION 14.1 • n=7 Participants	57.0 years STANDARD_DEVIATION 4.2 • n=5 Participants	50.3 years STANDARD_DEVIATION 12.5 • n=4 Participants	54.7 years STANDARD_DEVIATION 12.9 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 14

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

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

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment	2.5 units on a scale Standard Deviation 3	5.3 units on a scale Standard Deviation 3.8	4.5 units on a scale Standard Deviation 5.0	1 units on a scale Standard Deviation NA Only one measurement

SECONDARY outcome

Timeframe: Index hospitalization, up to 46 days

Population: Intention to treat (1 participant who withdrew not included)

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Number of Participants Who Died During the Index Hospitalization	1 Participants	2 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Intention to treat (1 participant who withdrew excluded)

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Number of Days on Mechanical Ventilation	5.5 days Standard Deviation 11	8.67 days Standard Deviation 15	0 days Standard Deviation 0	0 days Standard Deviation NA Only 1 observation

SECONDARY outcome

Timeframe: Index hospitalization, up to 46 days

Population: Intention to treat excluding 1 participant who withdrew

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization	1 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 28

Population: Intention to treat excluding 1 participant who withdrew

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

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
WHO Ordinal Scale Measured at 28 Days After Enrollment	2.8 score on a scale Standard Deviation 3.5	5.3 score on a scale Standard Deviation 3.8	4.5 score on a scale Standard Deviation 5.0	1 score on a scale Standard Deviation NA Only 1 participant

SECONDARY outcome

Timeframe: Index hospitalization, up to 46 days

Population: Intention to treat excluding 1 participant who withdrew

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Hospital Length of Stay in Days for the Index Hospitalization	9 days Standard Deviation 11	14.7 days Standard Deviation 14.6	2.5 days Standard Deviation 0.7	6 days Standard Deviation NA Only 1 participant

SECONDARY outcome

Timeframe: Index hospitalization, up to 46 days

Population: Intention to treat excluding 1 participant who withdrew

Number of participants who discontinued study medication for any reason

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Number of Participants With All-cause Study Medication Discontinuation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 14

Population: Intention to treat excluding 1 participant who withdrew

Outcome measures

Measure	Standard of Care Plus Hydroxychloroquine n=4 Participants Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 Participants Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 Participants Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care n=1 Participants Standard of care: Standard of care
Number of Participants With Severe Adverse Events	1 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Standard of Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard of Care Plus Hydroxychloroquine

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Standard of Care Plus Azithromycin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 2 deaths

Standard of Care Plus Hydroxychloroquine Plus Azithromycin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Standard of Care n=1 participants at risk Standard of care: Standard of care	Standard of Care Plus Hydroxychloroquine n=4 participants at risk Standard of care plus hydroxychloroquine for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5	Standard of Care Plus Azithromycin n=3 participants at risk Standard of care plus azithromycin for 5 days Standard of care: Standard of care Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5	Standard of Care Plus Hydroxychloroquine Plus Azithromycin n=2 participants at risk Standard of care plus hydroxychloroquine plus azithromycin for 5 days Standard of care: Standard of care Hydroxychloroquine: Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5 Azithromycin: Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Renal and urinary disorders Acute renal failure	0.00% 0/1 • 2 months	25.0% 1/4 • Number of events 1 • 2 months	0.00% 0/3 • 2 months	0.00% 0/2 • 2 months
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/1 • 2 months	25.0% 1/4 • Number of events 1 • 2 months	33.3% 1/3 • Number of events 1 • 2 months	0.00% 0/2 • 2 months

Other adverse events

Adverse event data not reported

Additional Information

Jason Stout, MD, MHS

Duke University

Phone: 919-668-0826

Email: jason.stout@dm.duke.edu

Results disclosure agreements

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