Efficacy of Losartan in Hospitalized Patients With COVID-19–Induced Lung Injury
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
No abstract available
Article activity feed
-
-
SciScore for 10.1101/2021.08.25.21262623: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: 18 The protocol was approved by a central institutional review board (Advarra, Pro00042757) and conducted following good clinical practice guidelines under the oversight of an independent data safety monitoring board.
Consent: All participants or their legally authorized representatives (LARs) provided written electronic informed consent.Sex as a biological variable not detected. Randomization Study design: We conducted a prospective multicenter blinded randomized placebo-controlled trial of hospitalized patients with COVID-19 at 13 hospitals in the United States from April 2020 to February 2021 following CONSORT guidelines. Blinding Participants >=18 years old were potentially eligible if … SciScore for 10.1101/2021.08.25.21262623: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: 18 The protocol was approved by a central institutional review board (Advarra, Pro00042757) and conducted following good clinical practice guidelines under the oversight of an independent data safety monitoring board.
Consent: All participants or their legally authorized representatives (LARs) provided written electronic informed consent.Sex as a biological variable not detected. Randomization Study design: We conducted a prospective multicenter blinded randomized placebo-controlled trial of hospitalized patients with COVID-19 at 13 hospitals in the United States from April 2020 to February 2021 following CONSORT guidelines. Blinding Participants >=18 years old were potentially eligible if exhibiting at least one CDC-recognized symptom of COVID-19.19 Exclusion criteria included: active outpatient treatment with an ACE-i, ARB, or aliskiren; prior adverse reaction to ACE-i/ARB; pregnancy, breastfeeding, or lack of contraception; history of dialysis, stage IV chronic kidney disease, or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2; potassium >5.0 mmol/L; history of severe liver disease; enrollment in another blinded clinical trial for COVID-19; lack of informed consent; inability to randomize within 48 hours of admission or positive test; oxygen saturation at baseline; or respiratory sequential organ failure assessment (SOFA) score of <1 (defined as P/F of <400, utilizing SaO2 if PaO2 is unavailable). Power Analysis Power and sample size: Due to a paucity of data at study design, we based expected variance of P/F on prior studies of viral-induced acute lung injury, considering standard deviations (SD) between 50-125.32–35 At a sample size of 200 with a 1:1 allocation ratio, we calculated 90% power to detect a difference of 70 in the P/F ratio assuming SD 150, and 80% to detect a 50-unit difference, assuming SD 125. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several limitations to consider with this study. The trial was initiated early in the pandemic, and temporal changes in clinical care including introduction of dexamethasone and remdesivir may have biased the trial towards the null. Our findings may also be consistent with the hypothesis that the RAAS does not play a significant role in SARS-CoV-2-related acute lung injury relative to other inflammatory pathways. Our choice of primary efficacy outcome required differential imputation methods based on whether or not the participant was treated with positive pressure ventilation, potentially affecting the results. However, the lack of effect on oxygen or mechanical ventilation-free days decreases the likelihood a larger study would identify clinically meaningful effects. While we detected sufficient concentrations of losartan, it remains possible lung parenchymal penetration is limited, mitigating potential efficacy. The relatively small sub-group undergoing RAAS measurement may have been underpowered to detect treatment effects. It remains possible that certain subgroups may benefit from ARB treatment that we could not identify due to inadequate subgroup sample size, including patients who may have RAAS dysregulation at baseline prior to infection. Finally, we cannot necessarily generalize these findings to other ARBs, ACE inhibitors, or other agents that modulate the RAAS.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04312009 Completed Losartan for Patients With COVID-19 Requiring Hospitalizatio… NCT043112009 Trial number did not resolve on clinicaltrials.gov. Is the number correct? NA Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
