Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial
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Abstract
Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml −1 , 85.9% ( n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.
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SciScore for 10.1101/2021.05.16.21257283: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The protocol was approved by the National Ethics Committee of Greece (approval 161/20) and by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS in Rome (01.02.2021) (EudraCT number, 2020-005828-11; ClinicalTrials.gov NCT04680949).
Consent: All patients or their legal representatives provided written informed consent before enrollment.Sex as a biological variable not detected. Randomization Patients with suPAR 6 ng/ml or more were electronically 1:2 randomized into treatment with placebo or anakinra using four randomization strata: classification into moderate or severe disease using the WHO definition6; need for dexamethasone intake; body … SciScore for 10.1101/2021.05.16.21257283: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The protocol was approved by the National Ethics Committee of Greece (approval 161/20) and by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS in Rome (01.02.2021) (EudraCT number, 2020-005828-11; ClinicalTrials.gov NCT04680949).
Consent: All patients or their legal representatives provided written informed consent before enrollment.Sex as a biological variable not detected. Randomization Patients with suPAR 6 ng/ml or more were electronically 1:2 randomized into treatment with placebo or anakinra using four randomization strata: classification into moderate or severe disease using the WHO definition6; need for dexamethasone intake; body mass index (BMI) more than 30 kg/m2; and country. Blinding Administration was done by a blind study nurse. Power Analysis Statistical analysis: The sample size was calculated based on the finding from the phase II SAVE trial5 that 42% of comparators and 16.3% of anakinra-treated patients by day 28 were presented with 6 or more points of the WHO-CPS. Table 2: Resources
Software and Algorithms Sentences Resources Analysis was conducted using IBM SPSS Statistics v. 26.0. SPSSsuggested: (SPSS, RRID:SCR_002865)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04680949 Active, not recruiting suPAR-Guided Anakinra Treatment for Management of Severe Res… 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.
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