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Treating COVID-19 With Hydroxychloroquine (TEACH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04369742
Recruitment Status : Recruiting
First Posted : April 30, 2020
Last Update Posted : May 1, 2020
Sponsor:
Collaborator:
State University of New York - Downstate Medical Center
Information provided by (Responsible Party):
NYU Langone Health

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Hydroxychloroquine (HCQ) Other: Pacebo: Calcium citrate Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 626 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Placebo-controlled, Randomized
Masking: Double (Participant, Care Provider)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: Treating COVID-19 With Hydroxychloroquine: A Multicenter Randomized, Double-blind, Placebo-controlled Clinical Trial in Hospitalized Adults
Actual Study Start Date : April 15, 2020
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Hydroxychloroquine
N= 313
Drug: Hydroxychloroquine (HCQ)
HCQ 400mg (2 tab) by mouth BID (day 1), 200mg (1 tab) by mouth BID (days 2-5)

Placebo Comparator: Placebo
N= 313
Other: Pacebo: Calcium citrate
Calcium citrate 2 tablets (400mg) BID on day 1, 1 tablet (200mg) on days 2-5




Primary Outcome Measures :
  1. Cumulative incidence of SAEs through day 30 [ Time Frame: 30 days ]
  2. Cumulative incidence of grade 3 or 4 AEs through day 30 [ Time Frame: 30 days ]
  3. Incidence of discontinuation of therapy (for any reason) [ Time Frame: 30 days ]
  4. Severe disease progression composite outcome [ Time Frame: 14 days ]
    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)


Secondary Outcome Measures :
  1. Cumulative incidence of events [ Time Frame: 30 days ]
    Events = mortality, ICU admission, invasive mechanical ventilation, ECMO, and/or hypotension requiring vasopressor support

  2. Hospital length of stay [ Time Frame: 30 days ]
    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)

  3. Days of fever [ Time Frame: 14 days ]
    Defined as number of days with temperature >100.4 degrees Fahrenheit.

  4. Days of non-invasive ventilator use [ Time Frame: 14 days ]
    Defined as days the patient is placed on non-invasive ventilator support (CPAP or BiPAP), excluding routine CPAP use for sleep apnea.

  5. Days of non-rebreather mask oxygen supplementation [ Time Frame: 14 days ]
    Defined as the number of days the subject was on a non-rebreather mask.

  6. Score on Cytokine Release Syndrome (CRS) Grading Scale [ Time Frame: Day 1 ]
    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).

  7. Score on Cytokine Release Syndrome (CRS) Grading Scale [ Time Frame: Day 6 ]
    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).

  8. Percentage of subjects reporting each severity score on 8 point ordinal scale Day 1 and EOT (End of Treatment - Day 6) [ Time Frame: 6 days ]
    The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

  9. Percentage of subjects with qTC prolongation at EOT [ Time Frame: 6 Days ]
    (≥470 milliseconds in men; ≥480 milliseconds in women) on electrocardiogram at EOT (Day 6)

  10. Cumulative Incidence of mortality [ Time Frame: 30 days ]
    Individual component of severe disease progression composite endpoint evaluated

  11. Cumulative Incidence of ICU admission [ Time Frame: 30 Days ]
    Individual component of severe disease progression composite endpoint evaluated

  12. Cumulative Incidence of Invasive mechanical ventilation [ Time Frame: 30 Days ]
    Individual component of severe disease progression composite endpoint evaluated

  13. Cumulative Incidence of ECMO [ Time Frame: 30 Days ]
    Individual component of severe disease progression composite endpoint evaluated

  14. Cumulative Incidence of hypotension requiring vasopressor support [ Time Frame: 30 Days ]
    Individual component of severe disease progression composite endpoint evaluated

  15. SARS-CoV-2 viral eradication from nasopharyngeal specimens at EOT [ Time Frame: 6 days ]
    Laboratory endpoint, measured by RT-PCR

  16. Change in Alanine Aminotransferase (ALT) levels [ Time Frame: Baseline, 6 days ]
    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).

  17. Change in Aspartate Aminotransferase (AST) levels [ Time Frame: Baseline, 6 days ]
    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).

  18. Change in Creatinine levels [ Time Frame: Baseline, 6 days ]
    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).

  19. Change in Glucose levels [ Time Frame: Baseline, 6 days ]
    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).

  20. Change in White Blood Cell (WBC) count [ Time Frame: Baseline, 6 days ]
    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).

  21. Change in Hemoglobin levels [ Time Frame: Baseline, 6 days ]
    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).

  22. Change in Platelet count [ Time Frame: Baseline, 6 days ]
    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).

  23. Change in total bilirubin levels [ Time Frame: Baseline, 6 days ]
    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).

  24. Change in Lactate Dehydrogenase (LDH) levels [ Time Frame: Baseline, 6 days ]
    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).

  25. Change in C-Reactive Protein (CRP) levels [ Time Frame: Baseline, 6 days ]
    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).

  26. Change in Interleukin 6 (IL-6) levels [ Time Frame: Baseline, 6 days ]
    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).


Other Outcome Measures:
  1. Titers of serum anti-SARS-CoV-2 antibodies [ Time Frame: 8 weeks ]
    A titer is the concentration of an antibody. ELISA (enzyme-linked immunosorbent assay) is a plate-based assay technique designed for detecting and quantifying antibodies. Titers will be measured by ELISA.

  2. Antigen-specific T cell count [ Time Frame: 8 weeks ]
    Real-time polymerase chain reaction (real-time PCR), also known as quantitative polymerase chain reaction (qPCR) (a laboratory technique of molecular biology) will be used to measure antigen-specific T cell count.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369742


Contacts
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Contact: Mark Mulligan, MD, FIDSA 646-799-0778 mark.mulligan@nyulangone.org
Contact: Robert Ulrich, MD 929-336-7705 robert.ulrich@nyulangone.org

Locations
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United States, New York
State University of New York (SUNY) Downstate Medical Center Recruiting
Brooklyn, New York, United States, 11203
Contact: Jack A. DeHovitz, MD, MPH, MHCDS, FACP         
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Mark Mulligan, MD         
Sponsors and Collaborators
NYU Langone Health
State University of New York - Downstate Medical Center
Investigators
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Principal Investigator: Mark Mulligan, MD, FIDSA NYU Langone Health
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT04369742    
Other Study ID Numbers: 20-00463
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
Access Criteria: Requests should be directed to mark.mulligan@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

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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
Additional relevant MeSH terms:
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Hydroxychloroquine
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Antirheumatic Agents