Conclusions

Inseparable to the design of this trial, platform conclusions are generated through frequent adaptive analyses as data accrues. To date, REMAP-CAP has contributed to the knowledge about the best treatment of COVID-19 with several results:

ACE2 RAS DOMAIN (27 Feb 2022)

  • After interim review of safety data, the Data safety and Monitoring Board recommended stopping enrolment of critically ill patients into the domain, which is in phase 2. Enrolment of critically and non-critically patients was stopped pending review of additional data.
Antiplatelet DOMAIN (23 Jun 2021)
  • Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support–free days within 21 days. However, when looking at survival on its own we saw that both aspirin and clopidogrel may improve survival. Enrolment of critically and non-critically patients was stopped pending review of additional data.
CORTICOSTEROID DOMAIN
  • Glucocorticoids improve outcomes for hospitalized patients with COVID-19. Published in the Journal of the American Medical Association (1). Results also included in the WHO meta-analysis published in JAMA on the same day (2).

COVID-19 IMMUNE MODULATION DOMAIN

  • Tocilizumab and sarilumab reduce mortality and prevent progression to invasive mechanical ventilation or ECMO in critically ill patients with COVID-19. Results published in the New England Journal of Medicine (5).
  • Tocilizumab and Sarilumab have reached the statistical trigger for equivalence and are the best interventions in the domain. This domain is paused while the full analysis of all interventions included in this domain, including Anakinra and Interferon-β1a, is being completed.

COVID-19 ANTI-COAGULATION DOMAIN

  • Therapeutic anticoagulation is futile, and possibly harmful, in critically ill patients with COVID-19. Conclusion from the multi-platform RCT collaboration between REMAP-CAP ATTACC and ACTIV-4, pre-print available from MedRxiv (3)
  • Therapeutic anticoagulation improves outcomes in hospitalized patients with COVID-19 who are not admitted to an ICU with organ support. Conclusion from the multi-platform RCT collaboration between REMAP-CAP, ATTACC and ACTIV-4, pre-print available from MedRxiv (4).

COVID-19 IMMUNOGLOBULIN DOMAIN

  • Convalescent plasma does not improve outcomes for critically ill patients with COVID-19. Shortly after this REMAP-CAP platform conclusion, the RECOVERY trial announced no significant difference in 28-day mortality in that trial. In light of these results, the REMAP-CAP ITSC decided to pause recruitment in the Moderate State of this domain.

COVID-19 ANTIVIRAL DOMAIN

  • Lopinavir/ritonavir does not improve outcomes for critically ill patients with COVID-19. The manuscript is in preparation.
  • Hydroxychloroquine does not improve outcomes, and potentially harms patients with COVID-19.  Results available in a collaborative meta-analysis as a preprint (6). 
 
1. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. Jama. 2020;324(13):1317-29.
2. The WHO Rapid Evidence Appraisal for COVID-19 Therapies Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020;324(13):1330-41.
3. The REMAP-CAP, ACTIV4-a, ATTACC Investigators, Zarychanski R. Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report. medRxiv. 2021:2021.03.10.21252749.
4. Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, et al. Therapeutic Anticoagulation in Non-Critically Ill Patients with Covid-19. medRxiv. 2021:2021.05.13.21256846.
5. The REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. New England Journal of Medicine. 2021;384(16):1491-502.
6. Axfors C, Schmitt AM, Janiaud P, Van’t Hooft J, Abd-Elsalam S, Abdo EF, et al. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun. 2021;12(1):2349.
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