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Randomized Controlled Trial
. 2022 Feb 25;17(2):e0263591.
doi: 10.1371/journal.pone.0263591. eCollection 2022.

Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial

Westyn Branch-Elliman  1   2 , Ryan Ferguson  1   3 , Gheorghe Doros  1   4 , Patricia Woods  1 , Sarah Leatherman  1 , Judith Strymish  1 , Rupak Datta  5   6 , Rekha Goswami  7 , Matthew D Jankowich  8 , Nishant R Shah  9 , Thomas H Taylor  10 , Sarah T Page  1 , Sara J Schiller  1 , Colleen Shannon  1 , Cynthia Hau  1 , Maura Flynn  1 , Erika Holmberg  1 , Karen Visnaw  1 , Rupali Dhond  1   3 , Mary Brophy  1 , Paul A Monach  1
Affiliations
Randomized Controlled Trial

Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial

Westyn Branch-Elliman et al. PLoS One. .

Abstract

Importance and objective: The aim of this pragmatic, embedded, adaptive trial was to measure the effectiveness of the subcutaneous anti-IL-6R antibody sarilumab, when added to an evolving standard of care (SOC), for clinical management of inpatients with moderate to severe COVID-19 disease.

Design: Two-arm, randomized, open-label controlled trial comparing SOC alone to SOC plus sarilumab. The trial used a randomized play-the-winner design and was fully embedded within the electronic health record (EHR) system.

Setting: 5 VA Medical Centers.

Participants: Hospitalized patients with clinical criteria for moderate to severe COVID-19 but not requiring mechanical ventilation, and a diagnostic test positive for SARS-CoV-2.

Interventions: Sarilumab, 200 or 400 mg subcutaneous injection. SOC was not pre-specified and could vary over time, e.g., to include antiviral or other anti-inflammatory drugs.

Main outcomes and measures: The primary outcome was intubation or death within 14 days of randomization. All data were extracted remotely from the EHR.

Results: Among 162 eligible patients, 53 consented, and 50 were evaluated for the primary endpoint of intubation or death. This occurred in 5/20 and 1/30 of participants in the sarilumab and SOC arms respectively, with the majority occurring in the initial 9 participants (3/4 in the sarilumab and 1/5 in the SOC) before the sarilumab dose was increased to 400 mg and before remdesivir and dexamethasone were widely adopted. After interim review, the unblinded Data Monitoring Committee recommended that the study be stopped due to concern for safety: a high probability that rates of intubation or death were higher with addition of sarilumab to SOC (92.6%), and a very low probability (3.4%) that sarilumab would be found to be superior.

Conclusions and relevance: This randomized trial of patients hospitalized due to respiratory compromise from COVID-19 but not mechanical ventilation found no benefit from subcutaneous sarilumab when added to an evolving SOC. The numbers of patients and events were too low to allow definitive conclusions to be drawn, but this study contributes valuable information about the role of subcutaneous IL-6R inhibition in the treatment of hospitalized COVID-19 patients. Methods developed and piloted during this trial will be useful in conducting future studies more efficiently.

Trial registration: Clinicaltrials.gov-NCT04359901; https://clinicaltrials.gov/ct2/show/NCT04359901?cond=NCT04359901&draw=2&rank=1.

PubMed Disclaimer

Conflict of interest statement

WBE, PM, and JMS were site investigators for a study funded by Gilead Sciences (funds to institution). WBE was supported by NIH NHLBI 1K12HL138049-01. All other authors report no conflicts of interest to report. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Consort diagram.
See this image and copyright information in PMC

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