Trial NCT04312009
Publication Puskarich M, medRxiv, 2021 (preprint)
Dates: 2020-04-01 to 2021-02-28
Funding: Public/non profit (Bill and Melinda Gates Foundation, National Institutes of Health)
Conflict of interest: No
| Methods | |
| RCT Blinding: quadruple blinding | |
| Location :
Multicenter / USA Follow-up duration (days): 90 | |
| Inclusion criteria | 1)>=18 years old; 2) exhibiting at least one CDC-recognized symptom of COVID-19; 3)positive clinical RT-PCR SARS-CoV-2 result; 4)Hospitalized; 5) respiratory sequential organ failure assessment score of at least 1; 6)not already taking a renin angiotensin-aldosterone system (RAAS) inhibitor |
| Exclusion criteria | 1) active outpatient treatment with an ACE-i, ARB, or aliskiren; 2) prior adverse reaction to ACE-i/ARB; 3)pregnancy, breastfeeding, or lack of contraception; 4)history of dialysis, stage IV chronic kidney disease, or estimated glomerular filtration rate (eGFR) <30mL/min/1.73 m2; 5) potassium >5.0 mmol/L; 6)history of severe liver disease; 7)enrollment in another blinded clinical trial for COVID-19; 8)lack of informed consent; 9)inability to randomize within 48 hours of admission or positive test; 10)oxygen saturation at baseline; 11)respiratory sequential organ failure assessment (SOFA) score of <1 (defined as P/F of <400, utilizing SaO2 if PaO2 is unavailable) |
| Interventions | |
| Treatment
Losartan 50 mg orally twice a day if eGFR >60 mL/min/1.73 m2 for 10 days or until discharge; once a day if eGFR 30–60; discontinued if decreased eGFR <30, or if SAE suspected. |
|
| Control
Placebo | |
| Participants | |
| Randomized 205 participants (n1=101 / n2= 104) | |
| Characteristics of participants N=205 Mean age : 55.1 123 males Severity : Mild: n=* / Moderate: n=*/ Severe: n=* Critical: n=* | |
| Primary outcome | |
| In the register Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days | |
| In the report PaO2/FiO2 ratio on day 7 | |
| 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 |
Some concerns |
| General comment | In addition to the pre-print article, the trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The primary outcome in the article reflected that in the registry. Several secondary outcomes in the registry were not reported. The intervention treatment dosage is different in the registry from what was reported in the paper. The trial achieved its target sample size. |