Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19

Study Overview
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Brief Summary
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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.

Official Title
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Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19 (HAHPS): A Prospective Pragmatic Trial

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br> | Drug: Hydroxychloroquine<br>* 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.<br>|
| Active Comparator: Azithromycin<br> | Drug: Azithromycin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Assessed once on day 14 after enrollment (enrollment is day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital-free Days at 28 Days | Calculated as number of days patient not in hospital | Admission (day 1) to 28 days after admission (day 28) | 
| 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 | Admission (day 1) to 28 days after admission (day 28) | 
| ICU-free Days at 28 Days | Calculated as number of days patient not in an ICU | Admission (day 1) to 28 days after admission (day 28) | 
| 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. | Admission (day 1) to 14 days after admission (day 14) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Hydroxychloroquine, Azithromycin