COVID-19
Conditions
Keywords
SARS-CoV-2, Hydroxychloroquine, Azithromycin
Brief summary
This study will compare two drugs (hydroxychloroquine and azithromycin) to see if hydroxychloroquine is better than azithromycin in treating hospitalized patients with suspected or confirmed COVID-19.
Interventions
DRUGHydroxychloroquine
Patients in the hydroxychloroquine arm will receive hydroxychloroquine 400 mg by mouth twice daily for 1 day, then 200 mg by mouth twice daily for 4 days (dose reductions for weight \< 45 kg or GFR (glomerular filtration rate)\<50ml/min). For patients \< 45kg, doses will be halved. For patients with GFR\<50ml/min, the final dose of hydroxychloroquine will not be administered. If the patient has already received hydroxychloroquine prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total.
DRUGAzithromycin
Patients in the azithromycin arm will receive azithromycin 500 mg on day 1 plus 250 mg daily on days 2-5 (may be administered intravenously per clinician preference). If the patient has already received azithromycin prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total.
Sponsors
University of Utah
Intermountain Health Care, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (age ≥ 18 years) * Confirmed OR suspected COVID-19, * Confirmed: Positive assay for COVID-19 within the last 10 days * Suspected: Pending assay for COVID-19 WITH high clinical suspicion * Scheduled for admission or already admitted to an inpatient bed
Exclusion criteria
* Allergy to hydroxychloroquine or azithromycin * History of bone marrow transplant * Known G6PD deficiency * Chronic hemodialysis or Glomerular Filtration Rate \< 20ml/min * Psoriasis * Porphyria * Concomitant use of digitalis, flecainide, amiodarone, procainamide, propafenone, cimetidine, dofetilide, phenobarbital, phenytoin, or sotalol * Known history of long QT syndrome * Current known QTc\>500 msec * Pregnant or nursing * Prisoner * Weight \< 35kg * Seizure disorder * Severe liver disease * Outpatient use of hydroxychloroquine for treatment of a disease other than COVID-19 OR has received more than 2 days of hydroxychloroquine or azithromycin for suspected or confirmed COVID-19 * Patient has recovered from COVID-19 and/or is being discharged from the hospital on day of enrollment. * Treating physician refuses to allow patient participation in the study * Unable to obtain informed consent * Prior enrollment in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| COVID Ordinal Outcomes Scale at 14 Days | Assessed once on day 14 after enrollment (enrollment is day 0) | Improvement of clinical condition of the patient defined by the COVID-19 WHO ordinal Outcomes score. This scale reflects a range from uninfected to dead, where 0 is no clinical or virological evidence of infection, 1 is no limitation of activities, 2 is limitation of activities, 3 is hospitalized, no oxygen therapy, 4 is oxygen by mask or nasal prongs, 5 is non-invasive ventilation or high-flow oxygen, 6 is intubation and mechanical ventilation, 7 is ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation), and 8 is death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital-free Days at 28 Days | Admission (day 1) to 28 days after admission (day 28) | Calculated as number of days patient not in hospital |
| Ventilator-free Days at 28 Days (Number of Days Patient Not on a Ventilator) | Admission (day 1) to 28 days after admission (day 28) | Calculated as number of days that patient is not on a ventilator up to day 28 days after admission |
| ICU-free Days at 28 Days | Admission (day 1) to 28 days after admission (day 28) | Calculated as number of days patient not in an ICU |
| Time to a 1-point Decrease in the WHO Ordinal Recovery Score | Admission (day 1) to 14 days after admission (day 14) | Time to 1-point decrease in the WHO ordinal recovery score is defined as the number of days until the ordinal outcome score drops by 1 relative to baseline on the 8-point WHO COVID Ordinal Outcomes scale, which reflects a range from uninfected to dead, where 0 is no clinical or virological evidence of infection, 1 is no limitation of activities, 2 is limitation of activities, 3 is hospitalized, no oxygen therapy, 4 is oxygen by mask or nasal prongs, 5 is non-invasive ventilation or high-flow oxygen, 6 is intubation and mechanical ventilation, 7 is ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation), and 8 is death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Hydroxychloroquine: Patients in the hydroxychloroquine arm will receive hydroxychloroquine 400 mg by mouth twice daily for 1 day, then 200 mg by mouth twice daily for 4 days (dose reductions for weight \< 45 kg or GFR (glomerular filtration rate)\<50ml/min). For patients \< 45kg, doses will be halved. For patients with GFR\<50ml/min, the final dose of hydroxychloroquine will not be administered. If the patient has already received hydroxychloroquine prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total. | 42 |
| Azithromycin Azithromycin: Patients in the azithromycin arm will receive azithromycin 500 mg on day 1 plus 250 mg daily on days 2-5 (may be administered intravenously per clinician preference). If the patient has already received azithromycin prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total. | 43 |
| Total | 85 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Azithromycin | Total |
|---|---|---|---|
| Age, Continuous | 51 years | 58 years | 55 years |
| Comorbidities | 1 Scores on a scale | 0 Scores on a scale | 1 Scores on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 28 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) White | 26 Participants | 28 Participants | 54 Participants |
| Region of Enrollment United States | 42 participants | 43 participants | 85 participants |
| Sex: Female, Male Female | 19 Participants | 14 Participants | 33 Participants |
| Sex: Female, Male Male | 23 Participants | 29 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 42 | 1 / 43 |
| other Total, other adverse events | 3 / 42 | 2 / 43 |
| serious Total, serious adverse events | 0 / 42 | 0 / 43 |
Outcome results
Primary
COVID Ordinal Outcomes Scale at 14 Days
Improvement of clinical condition of the patient defined by the COVID-19 WHO ordinal Outcomes score. This scale reflects a range from uninfected to dead, where 0 is no clinical or virological evidence of infection, 1 is no limitation of activities, 2 is limitation of activities, 3 is hospitalized, no oxygen therapy, 4 is oxygen by mask or nasal prongs, 5 is non-invasive ventilation or high-flow oxygen, 6 is intubation and mechanical ventilation, 7 is ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation), and 8 is death.
Time frame: Assessed once on day 14 after enrollment (enrollment is day 0)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 14 WHO COVID Score: Hydroxychloroquine | COVID Ordinal Outcomes Scale at 14 Days | 2.0 score on a scale |
| Day 14 WHO COVID Score: Azithromycin | COVID Ordinal Outcomes Scale at 14 Days | 2.0 score on a scale |
Secondary
Hospital-free Days at 28 Days
Calculated as number of days patient not in hospital
Time frame: Admission (day 1) to 28 days after admission (day 28)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 14 WHO COVID Score: Hydroxychloroquine | Hospital-free Days at 28 Days | 18.5 Days |
| Day 14 WHO COVID Score: Azithromycin | Hospital-free Days at 28 Days | 21 Days |
Secondary
ICU-free Days at 28 Days
Calculated as number of days patient not in an ICU
Time frame: Admission (day 1) to 28 days after admission (day 28)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 14 WHO COVID Score: Hydroxychloroquine | ICU-free Days at 28 Days | 18 Days |
| Day 14 WHO COVID Score: Azithromycin | ICU-free Days at 28 Days | 19 Days |
Secondary
Time to a 1-point Decrease in the WHO Ordinal Recovery Score
Time to 1-point decrease in the WHO ordinal recovery score is defined as the number of days until the ordinal outcome score drops by 1 relative to baseline on the 8-point WHO COVID Ordinal Outcomes scale, which reflects a range from uninfected to dead, where 0 is no clinical or virological evidence of infection, 1 is no limitation of activities, 2 is limitation of activities, 3 is hospitalized, no oxygen therapy, 4 is oxygen by mask or nasal prongs, 5 is non-invasive ventilation or high-flow oxygen, 6 is intubation and mechanical ventilation, 7 is ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation), and 8 is death.
Time frame: Admission (day 1) to 14 days after admission (day 14)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 14 WHO COVID Score: Hydroxychloroquine | Time to a 1-point Decrease in the WHO Ordinal Recovery Score | 7 Days |
| Day 14 WHO COVID Score: Azithromycin | Time to a 1-point Decrease in the WHO Ordinal Recovery Score | 6 Days |
Secondary
Ventilator-free Days at 28 Days (Number of Days Patient Not on a Ventilator)
Calculated as number of days that patient is not on a ventilator up to day 28 days after admission
Time frame: Admission (day 1) to 28 days after admission (day 28)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 14 WHO COVID Score: Hydroxychloroquine | Ventilator-free Days at 28 Days (Number of Days Patient Not on a Ventilator) | 18 days |
| Day 14 WHO COVID Score: Azithromycin | Ventilator-free Days at 28 Days (Number of Days Patient Not on a Ventilator) | 18 days |