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Multi-site Adaptive Trials Using Hydroxycholoroquine for COVID-19 (MATCH)

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: NCT04370262
Recruitment Status : Recruiting
First Posted : April 30, 2020
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Joseph Conigliaro, Northwell Health

Brief Summary:
The overall objective of the study will be to evaluate the clinical efficacy of COVID-19 treatments consisting of standard of care (SOC) combined with pharmaceutical antiviral management using hydroxychloroquine, or SOC with hydroxychloroquine combined with high-dose intravenous famotidine, in hospitalized patients meeting nucleic acid diagnostic and radiologic criteria for COVID-19 disease. The trial will statistically compare the clinical benefit afforded by the two treatment strategies to internal historical "standard of care" data from Northwell patents treated without benefit of either hydroxychloroquine or high-dose famotidine. We will compare clinical outcomes associated with hydroxychloroquine and the addition of high-dose intravascular famotidine. The trial is designed to enroll at least 600 COVID-19 patients hospitalized with moderate to severe disease into each of the two active treatment arms, with a total enrollment target of at least 1200 patients. The proposed trial has been designed for rapid enrollment and completion and powered to support two interim analyses that will enable prompt assessment of benefits and risks of the two treatment groups while maintaining the rigorous gold standard of a randomized double blind clinical trial structure. Trial design has been guided by practical consideration of the current clinical context involving rapidly escalating demands on hospital staff and resources, and incorporates a minimalist approach employing existing laboratory information management systems and a clinically relevant binary primary outcome of 30-day endpoint of death or survival.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: HCQ + Intravenous Famotidine Drug: HCQ + Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-Blind, Multi-Arm Historical Control, Comparative Trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-site, Randomized, Double-Blind, Multi-Arm Historical Control, Comparative Trial of the Safety and Efficacy of Hydroxychloroquine, and the Combination of HCQ and Famotidine for the Treatment of COVID-19
Actual Study Start Date : April 7, 2020
Estimated Primary Completion Date : September 7, 2020
Estimated Study Completion Date : April 7, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: HCQ/Famotidine
Subjects in this study arm will receive a combination of oral hydroxychloroquine and intravenous famotidine. Famotidine Injection, 10mg/mL mixed with Normal Saline is given intravenously at 120mg (30% of 400 mg oral dose). The total daily dose proposed is 360mg/day famotidine IV for a maximum of 14 days, or hospital discharge, whichever comes first. Hydroxychloroquine sulfate 200mg tablets will be administered as per the current clinical protocol for COVID - 19; a loading dose of 400 mg BID on day 1, followed by 200 mg BID for 4 days, or a loading dose of 800 mg QD on day 1, followed by 400 mg QD for 4 days, as per site specific clinical protocol for COVID-19.
Drug: HCQ + Intravenous Famotidine
IV famotidine

Placebo Comparator: HCQ/Placebo
Subjects in this arm will receive hydroxychloroquine 200 mg tablets administered as per the current clinical protocol for COVID - 19; a loading dose of 400 mg BID on day 1, followed by 200 mg BID for 4 days, or a loading dose of 800 mg QD on day 1, followed by 400 mg QD for 4 days, as per site specific clinical protocol for COVID-19; and placebo infusion three times daily.
Drug: HCQ + Placebo
IV placebo

No Intervention: Historical Control
In this trial, historical controls refer to hospitalized patients who were not treated with hydroxychloroquine or famotidine during the early stages of the pandemic, between February 1, 2020 and March 26, 2021. Since hydroxycholoroquine became the standard of care (SOC) treatment for COVID shortly after this time period, it would not be feasible or ethical to randomize patients in this trial to a control arm that excluded the use of any active investigational medications. This study will instead review data previously collected on patients not treated with HCQ to compare to the active treatment arms.



Primary Outcome Measures :
  1. Mortality [ Time Frame: 30 days post hospitalization ]
    Mortality status


Secondary Outcome Measures :
  1. Virologic response to study treatment detected in blood [ Time Frame: Day 30 relative to admission Day 0 ]
    Percent change in PCR copy number from first measurement

  2. Virologic clearance in nasal swab and/or lower respiratory secretions [ Time Frame: Day 6 and Day 30 ]
    Presence or absence of SARS-CoV-2 Viral RNA in Nasopharyngeal swab or lower respiratory secretions

  3. Clinical Severity [ Time Frame: Measured on study Days 3, 5, 8, 11, 15 and 30. ]
    Measured by 7-point ordinal scale: from (1) death, to (7) not hospitalized, no limit on daily activities

  4. Clinical Severity [ Time Frame: Measured on study Days 3, 5, 8, 11, 15 and 30. ]
    Measured by National Early Warning Score (NEWS): vital sign based score from 0-20, higher score indicates higher degree of illness

  5. Clinical Severity [ Time Frame: Measured on study Days 3, 5, 8, 11, 15 and 30. ]
    Measured by duration of use of supplemental oxygen (if applicable)

  6. Clinical Severity [ Time Frame: Measured on study Days 3, 5, 8, 11, 15 and 30. ]
    Measured by duration of use of mechanical ventilation (if applicable)

  7. Clinical Severity [ Time Frame: Measured on study Days 3, 5, 8, 11, 15 and 30. ]
    Measured by duration of hospitalization


Other Outcome Measures:
  1. Incidence of New Onset Lymphopenia [ Time Frame: Through study completion, average of 30 days ]
    Incidence of new onset lymphopenia during hospitalization measured by blood draw



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:

  1. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
  2. Understands and agrees to comply with planned study procedures.
  3. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
  4. Subject consents to randomization within 24 hours of hospital admission.
  5. Has radiographic confirmed COVID-19 disease < 72 hours prior to randomization.
  6. Illness of any duration, and at least one of the following:

    • Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
    • Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, OR
    • Requiring mechanical ventilation and/or supplemental oxygen.
  7. Subjects do not require laboratory confirmation of the corona virus SARS-CoV-2 to determine eligibility
  8. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study (acceptable methods will be determined by the site).

Exclusion Criteria:

  1. Mild COVID-19 disease (minor clinical symptoms, imaging does not show signs of lung inflammation)
  2. Recent history of or any in-hospital exposure to investigational medications targeting COVID-19, including hydroxychloroquine if prescribed in excess of the dose prescribed in this protocol.
  3. ALT/AST > 5 times the upper limit of normal.
  4. Moderate renal insufficiency (creatinine clearance 30-50 mL/min) OR Stage 4 severe chronic kidney disease OR requiring dialysis (i.e. creatinine clearance <30 mL/min)
  5. Presence of retinal or visual field changes attributable to any 4-aminoquinoline compound.
  6. Known hypersensitivity to 4-aminoquinolone compounds
  7. History of or evidence of QT prolongation on ECG examination
  8. History of psoriasis or porphyria
  9. Absolute neutrophil count (ANC) is < 2000 mm3
  10. Pregnancy
  11. History of hepatic disease, Hepatitis C infection, or alcoholism
  12. History of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency
  13. Concomitant use of known hepatotoxic drugs
  14. Anticipated transfer to another hospital which is not a study site within 72 hours.
  15. Allergy to any study medication
  16. Known to be immunocompromised by disease or treatment for existing disease

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): NCT04370262


Contacts
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Contact: Julie DiGregorio, CCRP (516) 493-7950 jdigregori@northwell.edu

Locations
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United States, New York
Southside Hospital Recruiting
Bay Shore, New York, United States, 11706
Contact: Patricia Nadraus, RN    631-894-5078    pnadraus@northwell.edu   
Contact: Richard Dima, MD    516-881-7064    rdima@northwell.edu   
Sub-Investigator: Neubert Philippe, MD         
North Shore University Hospital Recruiting
Manhasset, New York, United States, 11030
Contact: Richard Dima, MD    516-881-7064    rdima@northwell.edu   
Sub-Investigator: Negin Hajizadeh, MD         
Northern Westchester Hospital Recruiting
Mount Kisco, New York, United States, 10549
Contact: Asha Mellor, CCRC    914-666-1366    amellor@northwell.edu   
Lenox Hill Hospital Recruiting
New York, New York, United States, 10075
Contact: Tamika Wong, MPH    212-434-4836    twong4@northwell.edu   
Sub-Investigator: John Boockvar, MD         
Long Island Jewish Medical Center Recruiting
Queens, New York, United States, 11040
Contact: Richard Dima, MD    516-881-7064    rdima@northwell.edu   
Staten Island University Hospital Recruiting
Staten Island, New York, United States, 10305
Contact: Amanda Tice, RN    718-226-6454    atice@northwell.edu   
Sponsors and Collaborators
Northwell Health
Investigators
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Principal Investigator: Joseph Conigliaro, MD Northwell Health
Publications:

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Responsible Party: Joseph Conigliaro, Vice Chairperson, Medicine, General Internal Medicine, Northwell Health
ClinicalTrials.gov Identifier: NCT04370262    
Other Study ID Numbers: 20-0268
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020

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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.: No
Keywords provided by Joseph Conigliaro, Northwell Health:
COVID-19
Coronavirus
Famotidine
Additional relevant MeSH terms:
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Famotidine
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs