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

NCT ID: NCT04328012

Last Updated: 2022-03-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-06
• Study Completion Date: 2021-12-01

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).

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.

Conditions

SARS-CoV-2 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Losartan

losartan 25 mg po QD X 14 days

Group Type: EXPERIMENTAL

Losartan

Intervention Type: DRUG

administered 14 days

Placebo

placebo QD X 14 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

administered 14 days

Interventions

Losartan

administered 14 days

Intervention Type: DRUG

Placebo

administered 14 days

Intervention Type: DRUG

Other Intervention Names

Cozaar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Reid Health

UNKNOWN

Sponsor Role: collaborator

Goshen Health System

OTHER

Sponsor Role: collaborator

Bassett Healthcare

OTHER

Sponsor Role: lead

Responsible Party

Daniel Freilich, MD

attending physician - hospitalist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Freilich, MD

Role: PRINCIPAL_INVESTIGATOR

Bassett Medical Center

Locations

Bassett Medical Center

Cooperstown, New York, United States

Countries

United States

References

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Other Identifiers

1581969

Identifier Type: -

Identifier Source: org_study_id