Intermediate dose heparin thromboprophylaxis among critically ill patients with COVID-19: a randomized clinical trial

In this international RCT of critically ill patients with COVID-19, intermediate-dose heparin did not improve OSFDs or survival compared with standard thromboprophylaxis. The posterior distribution suggests clinically meaningful benefit is unlikely. Consistent with prior randomized trials and meta-analyses, these findings do not support routine escalation to intermediate dosing. Major bleeding rates were low and similar between groups.

  • 10 March 2026
  • The Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia (REMAP-CAP) Investigators, Charlotte A. Bradbury, Bryan J. McVerry, Patrick R. Lawler, Derek C. Angus, Djillali Annane, Yaseen M. Arabi, Diptesh Aryal, Carly Au, Abigail Beane, Scott M. Berry, Lindsay R. Berry, Janis Best-Lane, Shailesh Bihari, Marc Bonten, Frank Brunkhorst, Aidan Burrell, Meredith Buxton, Marc Carrier, Maurizio Cecconi, Allen C. Cheng, Matthew Cove, Lennie P. G. Derde, Michelle A. Detry, Lise J. Estcourt, Dean A. Fergusson, Mark Fitzgerald, Rob A. Fowler, Ewan C. Goligher, Cameron Green, Rashan Haniffa, David A. Harrison, Leanne M. C. Hays, Alisa M. Higgins, Thomas Hills, Christopher M. Horvat, David T. Huang, Beverley J. Hunt, Nao Ichihara, Devachandran Jayakumar, Stephanie Keattch, Anand Kumar, Michael A. Laffan, Francois Lamontagne, Christine M. Leeper, Roger J. Lewis, Elizabeth Lorenzi, Sylvain A. Lother, John C. Marshall, Colin J. McArthur, Daniel F. McAuley, Anna McGlothlin, Shay P. McGuinness, Zoe K. McQuilten, Saskia Middeldorp, Susan Morpeth, Paul R. Mouncey, Srinivas Murthy, Matthew D. Neal, Alistair D. Nichol, Rachael L. Parke, Jane C. Parker, Svenja Peters, Lusi Felipe Reyes, Kathryn Rowan, Hiroki Saito, Marlene Santos, Christina T. Saunders, Roger E. G. Schutgens, Christopher W. Seymour, Manu Shankar Hari, Vanessa Singh, Simon J. Stanworth, Alexis F. Turgeon, Anne M. Turner, Frank L. van de Veerdonk, Anthony C. Gordon, Steve A. Webb, and Ryan Zarychanski,
  • Journal of Thrombosis and Haemostasis

BACKGROUND
The optimal thromboprophylaxis among critically ill adults with COVID19 is uncertain.

OBJECTIVES
To determine the effectiveness and safety of intermediate-dose heparin compared with standard low-dose thromboprophylaxis.

METHODS
In an ongoing adaptive platform trial (randomized embedded multifactorial adaptive platform for community-acquired pneumonia), critically ill patients with COVID-19 were randomized to intermediate-dose heparin or standard low-dose thromboprophylaxis. Interventions were continued in hospital for up to 14 days. The primary endpoint was organ support-free days (OSFDs), an ordinal outcome combining in-hospital survival and the number of days free of intensive care unit-based respiratory or cardiovascular organ support through 21 days. The primary analysis was an adjusted Bayesian hierarchical cumulative logistic model. An odds ratio (OR) > 1.0 represents an improved outcome with intermediate-dose heparin.

RESULTS
Between April 27, 2021 and November 25, 2023, 1255 critically ill adults with COVID-19 were enrolled from 78 sites in 15 countries, of whom 1254 completed follow-up (n = 572 intermediate-dose, n = 682 low-dose). Enrollment was terminated prior to reaching a prespecified statistical trigger due to declining case numbers and slow recruitment. Median age was 59 years, and 36.7% were female (n = 461/1255). The probability that intermediate-dose heparin improved OSFDs was 73.5% (OR, 1.06; 95% credible interval, 0.87, 1.30), which did not meet the prespecified superiority threshold of 99%. Hospital survival was 77.1% (441/572) and 76.7% (523/682) in the intermediate- and low-dose heparin groups, respectively (median adjusted OR, 1.14; 95% credible interval, 0.86, 1.52). Major bleeding occurred in 10 of 572 (1.7%) and 14 of 682 (2.1%) patients receiving intermediate and standard low doses, respectively.

CONCLUSION
Intermediate-dose heparin did not improve OSFDs or survival compared with standard thromboprophylaxis in critically ill patients with COVID-19. (ClinicalTrials.gov number: CT02735707).

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