Trial NCT02735707
Publication Derde L, REMAP-CAP, 2021 (preprint)
Dates: 3/25/2020 to 4/10/2021
Funding: Mixed (PREPARE consortium by the European Union; FP7-HEALTH-2013-INNOVATION-1; RECOVER consortium by the European Union Horizon 2020 research and innovation program; Australian National Health and Medical Research Council; Health Research Council of New Zealand; Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant; UK NIHR; NIHR Imperial Biomedical Research Centre; Health Research Board of Ireland; UPMC Learning While Doing Program; Translational Breast Cancer Research Consortium; Global Coalition for Adaptive Research; French Ministry of Health; Minderoo Foundation; Wellcome Trust Innovations Project; Netherlands Organization for Health Research and Development ZonMw; NIHR Research Professorship; NIHR Clinician Scientist Fellowship; Australian National Health and Medical Research Council Career Development Fellowship; Roche Products Ltd; Sanofi (Aventis Pharma Ltd); Swedish Orphan Biovitrum AB (Sobi); Faron Pharmaceuticals (drug provision in some countries)
)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / NA Follow-up duration (days): 90 | |
| Inclusion criteria | Participants aged > 18 years; suspected or microbiologically confirmed COVID-19; receiving or not respiratory or cardiovascular organ support within 24 hours in an ICU. |
| Exclusion criteria | Death deemed to be imminent and inevitable during the next 24 hours; one or more of the participant, substitute decision maker or attending physician are not committed to full active treatment; more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection or more than 24 hours elapsed since ICU admission; previous participation in this REMAP within the last 90 days; patient has already received any dose of one or more of any form of interferon, anakinra, tocilizumab, or sarilumab during this hospitalization; long-term therapy with any of these agents prior to this hospital admission; patient has been randomized in a trial evaluating an immune modulation agent for proven or suspected COVID-19 infection where the protocol of that trial requires ongoing administration of study drug; known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization; intention to prescribe systemic corticosteroids for any reason, other than participation in the Corticosteroid domain of this platform, is an exclusion criterion to receive IFN-β1a; known hypersensitivity to proteins produced by E. coli will result in exclusion criterion to receive anakinra; known or suspected pregnancy is an exclusion criterion to receive the anakinra, IFN-β1a, tocilizumab, and sarilumab interventions; a baseline alanine aminotransferase or an aspartate aminotransferase that is more than five times the upper limit of normal is an exclusion criterion to receive tocilizumab or sarilumab; a baseline platelet count < 50 x 109 / L is an exclusion criterion to receive tocilizumab or sarilumab. |
| Interventions | |
| Treatment 1 Tocilizumab (NA/NA) Co-Intervention: Standard care Duration : NA | |
| Control Standard care (NA/NA) Co-Intervention: Standard care Duration : NA | |
| Treatment 3 Sarilumab (NA/NA) Co-Intervention: Standard care Duration : NA | |
| Treatment 4 Anakinra (NA/NA) Co-Intervention: Standard care Duration : NA | |
| Participants | |
| Randomized 2253 participants n1=972/ n2=418/ n3=485n4=378 | |
| Characteristics of participants N=2253 Mean age : 60.3 1536 males Severity : Mild: n=0 / Moderate: n=4/ Severe: n=1482 Critical: n=730 | |
| Primary outcome | |
| In the register All-cause mortality [Time Frame: Day 90]; Days alive and not receiving organ support in ICU [Time Frame: Day 21] | |
| In the report An ordinal scale that is a composite of in-hospital mortality and duration of respiratory and cardiovascular organ support, censored at 21 days, where all deaths within hospital and up to day 90 were assigned the worst outcome | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated NA |
| 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 version of the article, the study registry and protocol were used in data extraction and risk of bias assessment. The report contains definite results of tocilizumab, sarilumab and anakinra from the Immune Modulation Therapy domain of the REMAP-CAP clinical trial (an international, adaptive platform trial). There is no change from the trial registration in the intervention and control treatments. The platform initially included only participants admitted to an intensive care unit and receiving respiratory or cardiovascular organ support, a moderate state enrolling hospitalized participants not receiving respiratory or cardiovascular organ support was added subsequently. A blinded International Trial Steering Committee (ITSC) closed all arms of the domain on April 10, 2021. The primary outcome indicated in the registry reflects the primary outcome reported in the paper. Adverse events are not reported. |