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).
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.
Drug: Losartan
administered 14 days
Other Name: Cozaar
Drug: Placebo
administered 14 days
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
Bassett Medical Center
Cooperstown, New York, United States
Daniel Freilich, MD, Principal Investigator
Bassett Medical Center