December 19, 2022

expert reaction to study reporting long-term outcomes in critically ill patients with COVID-19 in the REMAP-CAP Randomized Clinical Trial

A study published in JAMA looks at long-term (180-Day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Prof Sir Martin Landray, Professor of Medicine & Epidemiology, Oxford Population Health, University of Oxford, said:

“It is good to see that the previous report of benefit of interleukin-6 antagonists persists at 6 months.

“The results for antiplatelet treatment should be interpreted cautiously: The previous REMAP-CAP report of the effect of antiplatelet drugs on number of organ support-free days within 21 days of randomisation was stopped on the grounds of futility.  Now this report suggests 95% probability that antiplatelets (but not anticoagulants) reduce 6 month mortality.  The adjusted hazard ratio is 0.85 (15% reduction) but with 95% credible interval 0.71 – 1.02.  These results are based on combining the aspirin and P2Y12 (two different types of antiplatelet drug) groups (approx. 1000 participants) and comparing with usual care controls (approx. 500 participants).

“The RECOVERY trial randomised approx. 15,000 participants to aspirin vs. usual care alone, including 700 who were on invasive mechanical ventilation and 4000 who were on non-invasive ventilation at baseline.  There was no evidence of any effect of aspirin on 28-day mortality either overall or in any particular subgroup of patients.  There was a 1 day reduction in median time to discharge alive from hospital.

“Thus, whilst the latest results from REMAP-CAP raise the possibility (but are not conclusive) that the use of antiplatelet treatment in patients with severe COVID-19 may reduce long-term (6-month) mortality it would be wise to wait for the results of the much larger (10x larger) study of aspirin in the RECOVERY trial.  These results (including around 18 months of follow-up) should be available early in the 2023 along with the results for 4 treatments that have previously been shown to reduce 28-day mortality – dexamethasone, tocilizumab (an interleukin-6 antagonist), baricitinib, and monoclonal antibody treatment.”

‘Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial’ by Writing Committee for the REMAP-CAP Investigators was published in JAMA on Friday 16 December 2022.

DOI: 10.1001/jama.2022.23257

https://jamanetwork.com/journals/jama/fullarticle/2799870

Declared interests

Prof Sir Martin Landray: “Professor of Medicine & Epidemiology, Oxford Population Health (www.ndph.ox.ac.uk).

Chief Executive, Protas (www.protas.co.uk).

Co-lead RECOVERY trial (www.recoverytrial.net).

Grant funding to University of Oxford from MRC, NIHR, Wellcome, Novartis, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme.

Study drug for RECOVERY trial provided by Roche, Regeneron, AbbVie, GSK/Vir, Boehringer Ingelheim.

Grant funding to Protas (not-for-profit company) from NHS England, Schmidt Futures, Google Ventures, Flu Lab, Sanofi, Regeneron, Wellcome, Bill & Melinda Gates Foundation.

He has no financial interest/investment in, and does not accept, honoraria payments directly or indirectly from, the pharmaceutical, food, tobacco, or alcohol industries.”