Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19
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Abstract
Background
The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).
Methods
In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus.
Results
In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was −0.28 log10 copies/mL (95% confidence interval [CI], −.51 to −.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%–74.0%). No safety concerns were noted.
Conclusions
In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.
Clinical Trials Registration
NCT04426695.
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SciScore for 10.1101/2021.11.05.21265656: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Patients were randomized 1:1:1 to 2.4 g REGEN-COV (1.2 g casirivimab and 1.2 g imdevimab), 8.0 g REGEN-COV (4.0 g casirivimab and 4.0 g imdevimab), or placebo as a single intravenous dose. Blinding not detected. Power Analysis not detected. 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:The absence of full representation across the spectrum of hospitalized patients on …
SciScore for 10.1101/2021.11.05.21265656: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Patients were randomized 1:1:1 to 2.4 g REGEN-COV (1.2 g casirivimab and 1.2 g imdevimab), 8.0 g REGEN-COV (4.0 g casirivimab and 4.0 g imdevimab), or placebo as a single intravenous dose. Blinding not detected. Power Analysis not detected. 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:The absence of full representation across the spectrum of hospitalized patients on varying degrees of oxygen support is a limitation of this study. Additionally, this study was prematurely terminated due to slow recruitment prior to the current surge associated with the emergence of the Delta variant. As a result of the smaller sample size, key analyses pooled the two patient cohorts as well as the two doses. Sensitivity analyses did not reveal major efficacy differences across the cohorts or doses; minor variability in the magnitude of risk reductions, with greater effects for the 2.4 g dose compared to the 8.0 g dose, was likely due to small numbers within each group suggesting that either dose can be utilized in hospitalized individuals requiring low-flow or no supplemental oxygen. Overall, trends for treatment benefit on mortality and other efficacy endpoints extend the observations in the larger RECOVERY trial, where benefit was seen in all patients regardless of respiratory status. Authorized options for intervention with a monoclonal antibody anti-viral treatment have been restricted to outpatients with Covid-19 or as post-exposure prophylaxis.5-7 Taken together with reports from the RECOVERY trial, these data support REGEN-COV representing a well-tolerated and compelling treatment option to reduce the risk of mortality in hospitalized Covid-19 patients and across the disease continuum of SARS-CoV-2, from prevention to hospitalization.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04426695 Completed Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-Co… 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.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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