SARS-CoV-2 Infection
Conditions
Keywords
COVID, COVID-19, coronavirus
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.
Interventions
DRUGLosartan
administered 14 days
DRUGPlacebo
administered 14 days
Sponsors
Reid Health
Goshen Health System
Bassett Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized, double blind, placebo controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS) | 60 days | difference in NCOSS scores between the different treatment groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital length of stay (LOS) | 60 days | difference in the total inpatient LOS between the three treatment groups |
| Intensive care unit level LOS | 60 days | difference in the total ICU level care LOS between the three treatment groups |
| Mechanical ventilation | 60 days | difference in length of use of mechanical ventilation between the three treatment groups |
| survival | 60 days | difference in all cause mortality between the four treatment groups |
Countries
United States
Outcome results
None listed