Treating COVID-19 With Hydroxychloroquine (TEACH)

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

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 Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine (HCQ); Drug: Placebo: Calcium citrate

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of New York (SUNY) Downstate Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: State University of New York - Downstate Medical Center
• Investigators: Principal Investigator: Mark Mulligan, MD, FIDSA, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: April 25, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Calcium-Regulating Hormones and Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Calcium; Hydroxychloroquine
• Other Study ID Numbers: 20-00463

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: [contact information for PI or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: Requests should be directed to mark.mulligan@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes