This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: 1. Standard of care alone 2. Standard of care plus hydroxychloroquine 3. Standard of care plus azithromycin 4. Standard of care plus hydroxychloroquine plus azithromycin
Other: Standard of care
Standard of care
Drug: 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
Drug: 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
Inclusion Criteria:
1. Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR
develop symptoms of COVID-19 during hospitalization
2. Subject (or legally authorized representative) can provide written informed consent
(in English or Spanish) affirming intention to comply with planned study procedures
prior to enrollment
3. Male or female adult aged 12 years or older at the time of enrollment
4. Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid
amplification assay (public health or commercial) in any respiratory specimen
collected within 14 days of randomization
5. Illness of any duration that includes
- Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR
- Clinical documentation of lower respiratory symptoms (cough, shortness of breath,
wheezing) OR
- Any documented SpO2 ≤ 94% on room air OR
- Any inpatient initiation or supplemental oxygen regardless of documented cause
Exclusion Criteria:
1. Participating in any other clinical trial of an experimental agent for COVID-19
2. On hydroxychloroquine at any time during hospitalization, or within 180 days of
hospitalization for COVID-19 regardless of indication
3. History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any
classification
4. Most recent ECG prior to time of screening with QTc of ≥500 msec
5. Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives
6. Death anticipated within 48 hours of enrollment
7. Inability to obtain informed consent from the patient or designated medical decision
maker
Duke Regional Hospital
Durham, North Carolina, United States
Duke University Hospital
Durham, North Carolina, United States
Durham VA Medical Center
Durham, North Carolina, United States
Duke Raleigh Hospital
Raleigh, North Carolina, United States
Jason Stout, MD, Principal Investigator
Duke University Hospital