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COVID MED Trial - Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 (COVIDMED)

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: NCT04328012
Recruitment Status : Recruiting
First Posted : March 31, 2020
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Daniel Freilich, MD, Bassett Healthcare

Brief Summary:
Although a number of therapeutics are being utilized by clinicians to treat patients with COVID-19, none have been systematically evaluated in clinical trials. Lopinavir/ritonavir, an antiretroviral medication, showed equivocal but possibly positive efficacy and safety in a RCT conducted in China and published in NEJM in March of 2020. Hydroxychloroquine, an antimalarial and anti-inflammatory medication, has shown potent antiviral activity in vitro and elimination of viral shedding in a small pilot clinical trial. Losartan, an angiotensin II receptor blocker (ARB), has theoretical benefit as SARSCoV-2 appears to bind to lung tissue via Angiotensin-Converting Enzyme 2 (ACE-2) receptors which might be inhibited by ARBs. This pragmatic adaptive trial compares outcome in COVID-19 patients treated with lopinavir/ritonavir, hydroxychloroquine, losartan, and placebo.

Condition or disease Intervention/treatment Phase
SARS-CoV-2 Infection Drug: lopinavir/ritonavir Drug: Hydroxychloroquine Sulfate Drug: Losartan Drug: Placebos Phase 2 Phase 3

Detailed Description:
In a randomized, double-blind, placebo-controlled, multi-center, Phase 2-like, investigator-directed trial, hospitalized adult patients with laboratory confirmed SARS-CoV-2 infection meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and if informed consent provided, enrolled randomly in a 2:2:2:1 ratio to one of four groups: Group 1 standard care and lopinavir/ritonavir, Group 2 standard care and hydroxychloroquine, Group 3 standard care and losartan, or Group 4 standard care and placebo. Patients will be followed for up to 60 days, with data collected to quantify the NCOSS over time (the primary objective), and for the trial's secondary objectives (see outcome measurements below).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, double blind, placebo controlled clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial)
Actual Study Start Date : April 6, 2020
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : April 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: lopinavir/ritonavir
lopinavir/ritonavir 400mg/200mg mg po BID X 5-14 days depending on availablity
Drug: lopinavir/ritonavir
administered for minimum of 5 days, up to 14 days if supply available
Other Name: Kaletra

Experimental: hydroxychloroquine
hydroxychloroquine sulfate 400 mg BID on Day 0 200 mg BID Days 1-4, days 1-13 if available
Drug: Hydroxychloroquine Sulfate
administered for minimum of 5 days, up to 14 days if supply available
Other Name: Plaquenil

Experimental: Losartan
losartan 25 mg po QD X 5-14 days depending on availability
Drug: Losartan
administered for minimum of 5 days, up to 14 days if supply available
Other Name: Cozaar

Placebo Comparator: Placebo
placebo BID X 14 days
Drug: Placebos
administered 14 days




Primary Outcome Measures :
  1. National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS) [ Time Frame: 60 days ]
    difference in NCOSS scores between the different treatment groups


Secondary Outcome Measures :
  1. Hospital length of stay (LOS) [ Time Frame: 60 days ]
    difference in the total inpatient LOS between the four treatment groups

  2. Intensive care unit level LOS [ Time Frame: 60 days ]
    difference in the total ICU level care LOS between the four treatment groups

  3. Mechanical ventilation [ Time Frame: 60 days ]
    difference in length of use of mechanical ventilation between the four treatment groups

  4. survival [ Time Frame: 60 days ]
    difference in all cause mortality between the four treatment groups



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. Hospitalized patient
  2. Laboratory confirmation of SARS-CoV-2 infection </= 72 hr prior to randomization
  3. Randomization within 72 hr of hospital admission
  4. Negative pregnancy test for reproductive age women
  5. Patient or LAR able to provide informed consent

Exclusion criteria, general (all groups)

  1. End stage renal disease (ESRD) NOT undergoing renal replacement therapy
  2. Severe hepatic insufficiency (LFTs > 5 times the upper limit of normal or known ESLD or cirrhosis)
  3. Nausea/vomiting or aspiration risk precluding oral medications unless can be given by gastric tube
  4. Use of another SARS-CoV-2 directed medication empirically or within another clinical trial within the prior week
  5. Pregnancy or breast feeding
  6. Absence of dependable contraception in reproductive age women
  7. Inability to obtain or declined informed consent

Exclusion criteria, group specific Group 1 (lopinavir/ritonavir)

  1. Allergy or intolerance to lopinavir/ritonavir
  2. Already taking lopinavir/ritonavir (within 1 month)
  3. Known HIV infection and/or taking antiretroviral therapy for another indication
  4. Co-administration with certain drugs due to CYP3A interactions if taken in < 24 hr

Group 2 (hydroxychloroquine)

  1. Allergy or intolerance to hydroxychloroquine (or chloroquine)
  2. Already taking hydroxychloroquine or chloroquine (within 1 month)
  3. Recent malaria exposure (within 1 month)
  4. History or current cardiac diseases (heart failure, ventricular arrhythmias, LBBB or RBBB, QTc prolongation)
  5. History of retinopathy
  6. Severe hypoglycemia
  7. Auditory disorders
  8. Known G6PD deficiency
  9. Porphyria or psoriasis
  10. Severe active alcohol use disorder (not in remission)
  11. Seizure disorder
  12. Co-administration of significant hepatotoxic agents (acetaminophen in standard dosing would not be included)
  13. Co-administration with certain drugs due to CYP3A interactions if taken in < 24 hr

Group 3 (losartan)

  1. Allergy or intolerance to losartan (or ACE inhibitors or other ARBs)
  2. Already taking ACE or ARB (within 1 month)
  3. Hypotension
  4. Hyperkalemia (K >/= 5.0 at time of screening or history of hyperkalemia)
  5. Blood pressure < 110/70 mm Hg or history of hypotension or recent (within 1 month) or recurrent syncope
  6. Severe renal dysfunction (estimated GFR < 30 ml/min at time of screening or history advanced renal disease)
  7. Severe volume depletion or acute kidney injury (AKI)
  8. Known cirrhotic ascites
  9. Known severe aortic or mitral valve stenosis
  10. Known unstented renal artery stenosis
  11. Co-administration with certain drugs due to CYP3A interactions if taken in < 24 hr

Group 4 (standard care [placebo])

1. None


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): NCT04328012


Contacts
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Contact: Jennifer Victory, RN 6075476965 jennifer.victory@bassett.org
Contact: daniel Freilich, MD 6075474586 daniel.freilich@bassett.org

Locations
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United States, New York
Bassett Medical Center Recruiting
Cooperstown, New York, United States, 13326
Contact: Kristin Pullyblank, RN, MS    607-547-6711    kristin.pullyblank@bassett.org   
Contact: Jennifer Victory, RN    6075476965 ext Victory    jennifer.victory@bassett.org   
Principal Investigator: daniel freilich, MD         
Sponsors and Collaborators
Bassett Healthcare
Investigators
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Principal Investigator: Daniel Freilich, MD Bassett Medical Center
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Responsible Party: Daniel Freilich, MD, attending physician - hospitalist, Bassett Healthcare
ClinicalTrials.gov Identifier: NCT04328012    
Other Study ID Numbers: 1581969
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: April 8, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Daniel Freilich, MD, Bassett Healthcare:
COVID
COVID 19
coronavirus
hydroxychloroquine
Additional relevant MeSH terms:
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Ritonavir
Lopinavir
Hydroxychloroquine
Losartan
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents