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

Duke University

Status and phase: Terminated; Phase 2

Conditions: SARS-CoV-2

Treatments: Drug: Hydroxychloroquine; Other: Standard of care; Drug: Azithromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT04335552

PRO00105339

Details and patient eligibility

About

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

Enrollment: 11 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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11 participants in 4 patient groups

Standard of care

Active Comparator group

Treatment:

Other: Standard of care

Standard of care plus hydroxychloroquine

Experimental group

Description:

Standard of care plus hydroxychloroquine for 5 days

Treatment:

Drug: Hydroxychloroquine

Other: Standard of care

Standard of care plus azithromycin

Experimental group

Description:

Standard of care plus azithromycin for 5 days

Treatment:

Drug: Azithromycin

Other: Standard of care

Standard of care plus hydroxychloroquine plus azithromycin

Experimental group

Description:

Standard of care plus hydroxychloroquine plus azithromycin for 5 days

Treatment:

Drug: Hydroxychloroquine

Drug: Azithromycin

Other: Standard of care