Clinical trial NCT04335552: Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
Official title: Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: SARS-CoV-2
Keywords: COVID-19
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-04-06
Enrollment: 11
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Patients will be initially randomized to one of two arms in a 1:1 ratio: 1) Standard of care treatment or 2) Standard of care treatment plus 5 days of hydroxychloroquine. Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy.
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment
timeFrame: Day 14
Secondary outcomes:
measure: Number of Participants Who Died During the Index Hospitalization
timeFrame: Index hospitalization, up to 46 days
measure: Number of Days on Mechanical Ventilation
timeFrame: Baseline
measure: Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization
timeFrame: Index hospitalization, up to 46 days
measure: WHO Ordinal Scale Measured at 28 Days After Enrollment
timeFrame: Day 28
measure: Hospital Length of Stay in Days for the Index Hospitalization
timeFrame: Index hospitalization, up to 46 days
measure: Number of Participants With All-cause Study Medication Discontinuation
timeFrame: Index hospitalization, up to 46 days
measure: Number of Participants With Severe Adverse Events
timeFrame: Day 14
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Regional Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Duke Raleigh Hospital
state: North Carolina
Study officials:
affiliation: Duke University Hospital
name: Jason Stout, MD
role: PRINCIPAL_INVESTIGATOR
References: