Treating COVID-19 With Hydroxychloroquine (TEACH)

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04369742
• Other study ID #: 20-00463
• Status: Terminated
• Phase: Phase 2
• Start date: April 15, 2020
• Est. completion date: April 1, 2021

Study information

• Verified date: April 2022
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 128
• Est. completion date: April 1, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Hydroxychloroquine (HCQ)
HCQ 400mg (2 tab) by mouth BID (day 1), 200mg (1 tab) by mouth BID (days 2-5)
• Placebo: Calcium citrate
Calcium citrate 2 tablets (400mg) BID on day 1, 1 tablet (200mg) on days 2-5

Locations

Country	Name	City	State
United States	State University of New York (SUNY) Downstate Medical Center	Brooklyn	New York
United States	NYU Langone Health	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	State University of New York - Downstate Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Days of Fever	Defined as number of days with temperature >100.4 degrees Fahrenheit.	14 days
Secondary	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
Secondary	Days of Non-rebreather Mask Oxygen Supplementation	Defined as the number of days the subject was on a non-rebreather mask.	14 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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