Trial NCT04315298
Publication Sivapalasingam S (2), 2021 (preprint)
Dates: 3/18/2020 to 7/2/2020
Funding: Private (Regeneron Pharmaceuticals, Inc. and Sanofi)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / USA Follow-up duration (days): 60 | |
| Inclusion criteria | >=18 years of age; hospitalized with laboratory-confirmed SARS-CoV-2 infection requiring supplemental oxygen and/or assisted ventilation |
| Exclusion criteria | In the opinion of the investigator, not expected to survive for more than 48 hoursfrom screening; Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count <2000 mm3, aspartate aminotransferase or alanine aminotransferase >5x upper limit of normal, platelets <50,000 per mm3; Treatment with antiââ¬âIL-6, antiââ¬âIL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period; Current treatment with the simultaneous combination of leflunomide and methotrexate; Exclusion criteria related to tuberculosis (TB)a. Known active TB or a history of incompletely treated TB b. Suspected or known extrapulmonary TB; Patients with suspected or known active systemic bacterial or fungal infections Note: Patients with a history of positive bacterial or fungal cultures but on enrollment do not have suspected or known active systemic bacterial or fungal infections may be enrolled; Participation in a double-blind clinical research study evaluating an investigational product or therapy within 3 months and less than 5 half-lives of investigational product prior to the screening visit Exception: The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, emergency use authorization, compassionate use protocol, or open-label use is permitted; Any physical examination findings, and/or history of any illness, concomitant medications, or recent live vaccines that, in the opinion of the study investigator,might confound the results of the study or pose an additional risk to the patient by their participation in the study; Known systemic hypersensitivity to sarilumab or the excipients of the drug product |
| Interventions | |
| Treatment 1 Sarilumab 400mg | |
| Control Placebo | |
| Treatment 3 Sarilumab 200mg | |
| Participants | |
| Randomized 1330 participants n1=567/ n2=286/ n3=477 | |
| Characteristics of participants N=1330 Mean age : NR 862 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=* Critical: n=* | |
| Primary outcome | |
| In the register Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with critical COVID-19 receiving mechanical ventilation at baseline [ Time Frame: Up to day 22 ] Phase 3 Cohort 1 | |
| In the report Proportion of critical patients receiving MV at baseline with ≥ 1-point improvement in clinical status on a 7-point ordinal scale from baseline to day 22 (phase 3) | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated NR |
| 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 with supplementary materials, the study registry was used in data extraction and risk of bias assessment. Study authors report that the trial was designed with an adaptive design allowing for changes to enrolment, interventions, and outcomes while the trial was ongoing. Several post-hoc changes were thus made to severity of patients eligible for enrolment, interventions, and outcomes during the course of the trial. Here we extracted pahse 3 cohort 1. Phase 2 and phase 3 cohorts 2 and 3 were also reported in this paper but extracted separately. |