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

SARS-CoV-2 Infection Clinical Trial

— COVIDMED  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04328012
• Other study ID #: 1581969
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: April 6, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: March 2022
• Source: Bassett Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: December 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2 Infection

Intervention

Drug:
• Losartan
administered 14 days
• Placebo
administered 14 days

Locations

Country	Name	City	State
United States	Bassett Medical Center	Cooperstown	New York

Sponsors (3)

Lead Sponsor	Collaborator
Bassett Healthcare	Goshen Health System, Reid Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS)	difference in NCOSS scores between the different treatment groups	60 days
Secondary	Hospital length of stay (LOS)	difference in the total inpatient LOS between the three treatment groups	60 days
Secondary	Intensive care unit level LOS	difference in the total ICU level care LOS between the three treatment groups	60 days
Secondary	Mechanical ventilation	difference in length of use of mechanical ventilation between the three treatment groups	60 days
Secondary	survival	difference in all cause mortality between the four treatment groups	60 days