Clinical trial NCT04369742: Treating COVID-19 With Hydroxychloroquine (TEACH)
Official title: Treating COVID-19 With Hydroxychloroquine: A Multicenter Randomized, Double-blind, Placebo-controlled Clinical Trial in Hospitalized Adults
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: State University of New York - Downstate Medical Center
First posted: 2020-04-30
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, Randomized
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. 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
2. Informed consent signed by patient
3. 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:

1. Presence of the primary endpoint (ICU admission, mechanical ventilation, ECMO, and/or vasopressor requirement) at time of randomization.
2. Treatment with CQ or HCQ within the 30 days prior to the start of the study drug treatment.
3. 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.
4. Unable to take oral medications.
5. History of allergic reaction or intolerance to CQ or HCQ.
6. Baseline corrected qT interval \>470 milliseconds (male) or \>480 milliseconds (female), history of congenital qT prolongation, and/or history of cardiac arrest.
7. Concomitant therapy with flecainide, amiodarone, digoxin, procainamide, propafenone, thioridazine, or pimozide
8. History of retinal disease including a documented history of diabetic retinopathy.
9. Known history of G6PD deficiency.

Primary outcomes:
measure: Percent of Participants With SAE Through Day 30
timeFrame: 30 days
measure: Percent of Participants With Grade 3 or 4 AEs Through Day 30
timeFrame: 30 days
measure: Percent of Participants With Discontinuation of Therapy (for Any Reason)
timeFrame: 30 days
measure: Percent of Participants Showing a Severe Disease Progression Composite Outcome
timeFrame: 14 days
Secondary outcomes:
measure: Hospital Length of Stay
timeFrame: 30 days
measure: Days of Fever
timeFrame: 14 days
measure: Days of Non-invasive Ventilator Use
timeFrame: 14 days
measure: Days of Non-rebreather Mask Oxygen Supplementation
timeFrame: 14 days
measure: Number of Participants With Mild, Moderate, and Severe Scores on Cytokine Release Syndrome (CRS) Grading Scale
timeFrame: Day 1
measure: Percent of Subjects With Q-T Interval, Corrected (qTC) Prolongation at End of Treatment (EOT)
timeFrame: 6 Days
measure: Percent of Patients Who Resulted in Mortality
timeFrame: 30 days
measure: Percent of Participants Who Required ICU Admission
timeFrame: 30 Days
measure: Percent of Participants Who Required Invasive Mechanical Ventilation
timeFrame: 30 Days
measure: Percent of Participants Who Required Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: 30 Days
measure: Percent of Participants With Hypotension Requiring Vasopressor Support
timeFrame: 30 Days
measure: Percent of Participants With SARS-CoV-2 Viral Eradication From Nasopharyngeal Specimens at EOT
timeFrame: 6 days
measure: Change in Alanine Aminotransferase (ALT) Levels
timeFrame: Baseline, 6 days
measure: Change in Aspartate Aminotransferase (AST) Levels
timeFrame: Baseline, 6 days
measure: Change in Creatinine Levels
timeFrame: Baseline, 6 days
measure: Change in Glucose Levels
timeFrame: Baseline, 6 days
measure: Change in White Blood Cell (WBC) Count
timeFrame: Baseline, 6 days
measure: Change in Hemoglobin Levels
timeFrame: Baseline, 6 days
measure: Change in Platelet Count
timeFrame: Baseline, 6 days
measure: Change in Total Bilirubin Levels
timeFrame: Baseline, 6 days
measure: Change in Lactate Dehydrogenase (LDH) Levels
timeFrame: Baseline, 6 days
measure: Change in C-Reactive Protein (CRP) Levels
timeFrame: Baseline, 6 days
measure: Change in Interleukin 6 (IL-6) Levels
timeFrame: Baseline, 6 days
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: State University of New York (SUNY) Downstate Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Mark Mulligan, MD, FIDSA
role: PRINCIPAL_INVESTIGATOR
References: