Covid-19 Living Data

Trial NCT04340557
Publication Geriak M, Infect Dis Ther, 2021 (published paper)
Dates: 2020-03-30 to 2020-07-04
Funding: Private (Sharp Healthcare Foundation)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA Follow-up duration (days): 45
Inclusion criteria	Confirmed COVID-19 positive test result (RT-PCR); Mild to moderate respiratory symptoms of COVID-19 - hypoxia (SpO2 ≤ 96% on ≥ 1 L/min O2 by nasal cannula) but not on mechanical ventilation; Systolic blood pressure ≥ 105 mmHg; Screen within 3 days of a positive COVID-19 test; Age ≥18 years old; Access to a phone in the hospital room or an electronic device that is capable of receiving phone or video calls; Able to read/write/speak English or Spanish fluently; Subjects must have the capacity to provide consent or an appropriate LAR to provide informed consent; Negative pregnancy test for women of childbearing potential.
Exclusion criteria	Severe allergy to any ARB or ACE-inhibitor, including angioedema; In the intensive care unit at screening; Home meds include any kind of ACE inhibitor or ARB; Acute Kidney Injury (50% reduction in GFR from baseline at admission to any time during treatment in the study treatment arm); Hyperkalemia >5.0 mmol/L at baseline or any time during treatment in the study treatment arm; Creatinine Clearance < 30 ml/min at baseline or any time during treatment in the study treatment arm.
Interventions
	Treatment Losartan 12.5 mg twice daily for up to 10 days. Dose could be escalated on judgement of treating physician.
	Control Standard care ( / ) Definition of Standard care: SOC consisted of the subject remaining on or being eligible for any treatment not part of a randomized clinical trial and considered standard of care at the time of enrollment. On May 13, 2020, and afterwards, this included the use of remdesivir. Patients were also eligible to receive convalescent plasma therapy as part of the nationally available compassionate use registry, which was informally accepted in our region as SOC.
Participants
	Randomized 32 participants (n₁=17 / n₂= 15)
	Characteristics of participants N=32 Mean age : 57.1 19 males Severity : Mild: n=0 / Moderate: n=32/ Severe: n=0 Critical: n=0
Primary outcome
	In the register Mechanical ventilation [ Time Frame: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 days ]
	In the report Receipt of mechanical ventilation or death before receiving ventilation (a composite of either receiving ventilation or the patient status changed to a do not resuscitate/do not intubate resulting in progressive respiratory failure and death).
Documents available	Protocol NR Statistical plan NR Data-sharing stated
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	High
General comment	In addition to the published article, the trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The authors report in the published article that the trial “was registered on clinicaltrials.gov (March 27, 2020; NCT04340557), inferring prospective registration. Clinicaltrials.gov reports the registration was first submitted on April 6, 2020, a week after start of recruitment. There were no differences between the registry and published article in population, procedures or interventions. There were some differences in the outcomes reported (receipt of mechanical ventilation or death before receiving ventilation, discharge without progression to ICU, ICU transfer, in-hospital mortality and length of hospital stay) and those in the registry (number requiring transfer into ICU for mechanical ventilation, number transferred from non-ICU bed to an ICU bed, number of days requiring oxygen therapy). Adverse events were not reported except for discontinuation due to tolerability/safety. Mortality was reported as in-hospital mortality. The study did not achieve its estimated sample size (n = 200; n = 32 randomized) and appears to have been terminated: “study enrollment dropped off consider- ably because of a rise in competing clinical trials”. The study was assessed to be at a high risk of bias due to some concerns in four of five domains.