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COVID MED Trial - Comparison Of Therapeutics for Hospitalized Patients Infected With COVID-19 (COVIDMED)

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ClinicalTrials.gov Identifier: NCT04328012
Recruitment Status : Recruiting
First Posted : March 31, 2020
Last Update Posted : February 16, 2021
Sponsor:
Collaborators:
Reid Health
Goshen Health System
Information provided by (Responsible Party):
Daniel Freilich, MD, Bassett Healthcare

Brief Summary:
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 2:1 ratio to one of two groups: Group 1 standard care and losartan or Group 2 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).

Condition or disease Intervention/treatment Phase
SARS-CoV-2 Infection Drug: Losartan Drug: Placebo Phase 2 Phase 3

Detailed Description:

Although a number of therapeutics have been utilized by clinicians to treat hospitalized patients with COVID-19, none were systematically evaluated in clinical trials at the time of the outset of this RCT (COVID MED). Since then, dexamethasone has been shown to decrease mortality and remdesivir to possibly decrease hospital LOS in the RECOVERY and ACTT-II trials and others. The initial iteration of this protocol included 4 arms, hydroxychloroquine, lopinavir/ritonavir, losartan, and placebo based on suggestive efficacy and safety and widespread empiric use. The current iteration of COVID MED includes two arms, standard of care and losartan vs. standard of care and placebo.

Hydroxychloroquine was initially included in COVID MED based on suggestive in vitro, animal preclinical, and early RCT data, and widespread empiric use in hospitalized patients with COVID-19. Lopinavir/ritonavir, an antiretroviral medication, showed equivocal and possibly positive efficacy and safety in an early pandemic Chinese RCT published in NEJM. After public release and eventual publication of the negative results for hydroxychloroquine and then lopinavir/ritonavir initially from the RECOVERY trial and then others, enrollment in COVID MED in these two arms was halted and then discontinued permanently. Data from subjects enrolled in the hydroxychloroquine arm are being incorporated into a pooled analysis of RCTs by the Trial Innovation Network.

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; other potential benefits have been hypothesized as well. Since the initial iteration of this protocol, observational studies have shown that patients already taking ACEi/ARB medications do not have adverse outcome when these drugs are continued in hospitalized COVID-19 patients. These data have reinforced continuation of the losartan vs. placebo arms of this RCT which are ongoing.

This pragmatic adaptive trial continues to compare outcome in hospitalized COVID-19 patients treated with standard of care and losartan vs. standard of care and placebo.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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 : June 1, 2021
Estimated Study Completion Date : August 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Losartan
losartan 25 mg po QD X 14 days
Drug: Losartan
administered 14 days
Other Name: Cozaar

Placebo Comparator: Placebo
placebo QD X 14 days
Drug: Placebo
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 three treatment groups

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

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

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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. Age >= 18 years
  3. Able to ingest oral medication or be administered medication via gastric tube or equivalent
  4. Laboratory confirmation of SARS-CoV-2 infection within 1 week prior to randomization
  5. Randomization within 72 hr of hospital admission
  6. Negative pregnancy test for reproductive age women
  7. Patient or LAR able to provide informed consent

Exclusion criteria

  1. Allergy or intolerance to losartan or other ARBs
  2. Already taking ACE or ARB (within 1 month)
  3. Hypotension at time of enrollment (SBP < 100 mm Hg)
  4. Hyperkalemia (K >/= 5.0 at time of screening or history of hyperkalemia)
  5. Severe renal dysfunction (estimated GFR < 30 ml/min at time of screening or history advanced renal disease)
  6. Severe volume depletion or acute kidney injury (AKI) at time of enrollment
  7. Known cirrhotic ascites
  8. Known severe aortic or mitral valve stenosis
  9. Known unstented renal artery stenosis
  10. Co-administration with certain drugs due to CYP3A interactions if taken in < 24 hr
  11. Severe hepatic insufficiency (LFTs > 5 times the upper limit of normal or known ESLD or cirrhosis)
  12. Nausea/vomiting or aspiration risk precluding oral medications unless can be given by gastric tube
  13. Pregnancy or breast feeding
  14. Absence of dependable contraception in reproductive age women
  15. Inability to obtain or declined informed consent

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
Reid Health
Goshen Health System
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: February 16, 2021
Last Verified: February 2021
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
Additional relevant MeSH terms:
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Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action