BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19 . The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown .
METHODS: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study . Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status . The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death . The main safety outcome was major bleeding .
RESULTS: Of 600 randomized patients , 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50 , 71) years; 237 (42.2 %) women), of whom 336 (59.8 %) survived to hospital discharge . The primary outcome occurred in 132 (47.8 %) of patients assigned to intermediate-dose and 130 (45.4 %) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21 , 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90 . Overall, there were 7 (2.5 %) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4 %) major bleeding events in the standard-dose group (none fatal) (HR : 1.82 , 95% CI : 0.53-6.24, P=0.33).
CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.