Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit - The INSPIRATION Randomized Clinical Trial
This study in Iran (n=600; 562 in primary analysis) found no difference between routine use of intermediate dose (enoxaparin 1mg/kg daily) and standard prophylactic anticoagulation (enoxaparin 40mg daily) in terms of the composite primary endpoint (45.7% v 44.1%).
Source:
Journal of the American Medical Association
SPS commentary:
The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomised patients who met the eligibility criteria and received at least 1 dose of the assigned treatment.
There were 7 (2.5%) major bleeding events in the intermediate-dose group and 4 (1.4%) in the standard-dose prophylactic anticoagulation group; the difference did not meet the criteria for non-inferiority of the intermediate dose to the standard dose for this safety endpoint.
The authors note that in line with their results, an interim analysis of critically ill patients enrolled in 3 trials testing therapeutic-dose vs standard prophylactic anticoagulation (ACTIV-4a, REMAP-CAP, and ATTACC) led the data and safety monitoring board to pause further enrolment because of futility for efficacy and potential excess of safety events.
They go on to discuss the limitations of their study and the potential reasons behind the observed lack of benefit, and note that there are numerous RCTs ongoing evaluating anticoagulants across the spectrum of Covid-19 illness severity, that could help identify effective therapies in various subgroups.