Treating COVID-19 With Hydroxychloroquine (TEACH)

Study Overview
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Brief Summary
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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.

Official Title
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Treating COVID-19 With Hydroxychloroquine: A Multicenter Randomized, Double-blind, Placebo-controlled Clinical Trial in Hospitalized Adults

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine (HCQ)
* Drug: Placebo: Calcium citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Hospitalized adult (≥18 years old) with symptoms consistent with COVID-19 including but not limited to any of the following: fever (documented or subjective), cough, dyspnea, diarrhea, nausea, diffuse myalgias, and/or anosmia Informed consent signed by patient Positive SARS-CoV-2 RT-PCR testing (nasopharyngeal, oropharyngeal, sputum and/or bronchoalveolar lavage) o The testing may: Occur up to ≤72h prior to informed consent of participation in the study Be undertaken either on-site or in an external laboratory certified by New York State to run testing for SARS-CoV-2 Exclusion Criteria An individual who meets any of the following criteria will be excluded from participation in this study: Presence of the primary endpoint (ICU admission, mechanical ventilation, ECMO, and/or vasopressor requirement) at time of randomization. Treatment with CQ or HCQ within the 30 days prior to the start of the study drug treatment. Participation in a clinical trial to investigate a non-FDA approved drug with the intent to treat SARS-CoV-2 within the 30 days prior to the start of the study drug treatment. Unable to take oral medications. History of allergic reaction or intolerance to CQ or HCQ. Baseline corrected qT interval >470 milliseconds (male) or >480 milliseconds (female), history of congenital qT prolongation, and/or history of cardiac arrest. Concomitant therapy with flecainide, amiodarone, digoxin, procainamide, propafenone, thioridazine, or pimozide History of retinal disease including a documented history of diabetic retinopathy. Known history of G6PD deficiency.

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
Interventional Model Description: Placebo-controlled, Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br> | Drug: Hydroxychloroquine (HCQ)<br>* HCQ 400mg (2 tab) by mouth BID (day 1), 200mg (1 tab) by mouth BID (days 2-5)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo: Calcium citrate<br>* Calcium citrate 2 tablets (400mg) BID on day 1, 1 tablet (200mg) on days 2-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With SAE Through Day 30 | The measure value is reported as a percentage (# of patients with outcome/ # of patients * 100) | 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) | 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) | 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). | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 30 days | 
| Days of Fever | Defined as number of days with temperature >100.4 degrees Fahrenheit. | 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. | 14 days | 
| Days of Non-rebreather Mask Oxygen Supplementation | Defined as the number of days the subject was on a non-rebreather mask. | 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). | 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) | 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). | 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). | 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). | 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). | 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) | 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 | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | Baseline, 6 days |