Treatments for COVID-19 are urgently needed. Hydroxychloroquine (HCQ) is an antimalarial and immunomodulatory agent being repurposed for COVID-19 therapy based off in vitro data suggesting a possible antiviral effect. However, HCQ's effect on COVID-19 in human infection remains unknown. To fill this knowledge gap, we will enroll 626 adult patients hospitalized with laboratory-confirmed COVID-19 and randomize them 1:1 to a five-day course of HCQ or placebo. Notable exclusion criteria include ICU admission or ventilation on enrollment, prior therapy with HCQ, and baseline prolonged qTC. Our primary endpoint is a severe disease progression composite outcome (death, ICU admission, mechanical ventilation, ECMO, , and/or vasopressor requirement) at the 14-day post-treatment evaluation. Notable secondary clinical outcomes include 30-day mortality, hospital length of stay, noninvasive ventilator support, and cytokine release syndrome (CRS) grading scale. Secondary exploratory objectives will examine SARS-CoV-2 viral eradication at the EOT, changes in COVID-19 putative prognostic markers and cytokine levels, and titers of anti-SARS-CoV-2 antibodies. This randomized trial will determine if HCQ is effective as treatment in hospitalized non-ICU patients with COVID-19.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
128
HCQ 400mg (2 tab) by mouth BID (day 1), 200mg (1 tab) by mouth BID (days 2-5)
Calcium citrate 2 tablets (400mg) BID on day 1, 1 tablet (200mg) on days 2-5
State University of New York (SUNY) Downstate Medical Center
Brooklyn, New York, United States
NYU Langone Health
New York, New York, United States
Percent of Participants With SAE Through Day 30
The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100)
Time frame: 30 days
Percent of Participants With Grade 3 or 4 AEs Through Day 30
The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100)
Time frame: 30 days
Percent of Participants With Discontinuation of Therapy (for Any Reason)
The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100)
Time frame: 30 days
Percent of Participants Showing a Severe Disease Progression Composite Outcome
Including any of the following: mortality, ICU admission, invasive mechanical ventilation, ECMO, and/or hypotension requiring vasopressor support by the 14-day post-treatment evaluation (PTE). The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100).
Time frame: 14 days
Hospital Length of Stay
LOS is defined as the interval (in days) that the patient was admitted to a non-rehabilitation floor, categorized as short (\<7 days), moderate (7-10 days), or extended (\>10 days)
Time frame: 30 days
Days of Fever
Defined as number of days with temperature \>100.4 degrees Fahrenheit.
Time frame: 14 days
Days of Non-invasive Ventilator Use
Defined as days the patient is placed on non-invasive ventilator support (CPAP or BiPAP), excluding routine CPAP use for sleep apnea.
Time frame: 14 days
Days of Non-rebreather Mask Oxygen Supplementation
Defined as the number of days the subject was on a non-rebreather mask.
Time frame: 14 days
Number of Participants With Mild, Moderate, and Severe Scores on Cytokine Release Syndrome (CRS) Grading Scale
Grade 1 (mild) = able to be managed with nonparenteral supportive care, Grade 2 (moderate) = at least one of the following present (hospitalization needed for management of CRS-related symptoms, parenteral nutrition or supportive care required, signs of moderate/severe organ dysfunction), Grade 3 (severe) = hospitalization needed for management of at least one of the following (hypotension, hypoxia, organ dysfunction, coagulopathy), Grade 4 (life-threatening) = at least one of the following present (hypotension requiring high-dose vasopressors, hypoxia requiring mechanical ventilation).
Time frame: Day 1
Percent of Subjects With Q-T Interval, Corrected (qTC) Prolongation at End of Treatment (EOT)
(≥470 milliseconds in men; ≥480 milliseconds in women) on electrocardiogram at EOT (Day 6)
Time frame: 6 Days
Percent of Patients Who Resulted in Mortality
Individual component of severe disease progression composite endpoint evaluated. The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100).
Time frame: 30 days
Percent of Participants Who Required ICU Admission
Individual component of severe disease progression composite endpoint evaluated. The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100).
Time frame: 30 Days
Percent of Participants Who Required Invasive Mechanical Ventilation
Individual component of severe disease progression composite endpoint evaluated. The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100).
Time frame: 30 Days
Percent of Participants Who Required Extracorporeal Membrane Oxygenation (ECMO)
Individual component of severe disease progression composite endpoint evaluated. The measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100).
Time frame: 30 Days
Percent of Participants With Hypotension Requiring Vasopressor Support
Individual component of severe disease progression composite endpoint evaluated. For incidence, the measure value is reported as a percentage (# of patients with outcome/ # of patients \* 100)
Time frame: 30 Days
Percent of Participants With SARS-CoV-2 Viral Eradication From Nasopharyngeal Specimens at EOT
Laboratory endpoint, measured by RT-PCR, reported as the percentage of negative results at day 6
Time frame: 6 days
Change in Alanine Aminotransferase (ALT) Levels
Biochemistry lab-work will be completed to obtain ALT levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Aspartate Aminotransferase (AST) Levels
Biochemistry lab-work will be completed to obtain AST levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Creatinine Levels
Biochemistry lab-work will be completed to obtain Creatinine levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Glucose Levels
Biochemistry lab-work will be completed to obtain Glucose levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in White Blood Cell (WBC) Count
Hematology lab-work will be completed to obtain WBC count (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Hemoglobin Levels
Hematology lab-work will be completed to obtain hemoglobin levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Platelet Count
Hematology lab-work will be completed to obtain platelet count (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Total Bilirubin Levels
Biochemistry lab-work will be completed to obtain bilirubin levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Lactate Dehydrogenase (LDH) Levels
Biochemistry lab-work will be completed to obtain LDH levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in C-Reactive Protein (CRP) Levels
Biochemistry lab-work will be completed to obtain CRP levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
Change in Interleukin 6 (IL-6) Levels
Biochemistry lab-work will be completed to obtain IL-6 levels (if not obtained as part of routine clinical care, the research team will order for clinical lab to add onto remnant specimens, if available).
Time frame: Baseline, 6 days
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