Intermediate vs Standard-dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to ICU: Ninety-day Results from the INSPIRATION Trial.

Bikdeli, Behnood; Talasaz, Azita H; Rashidi, Farid; Bakhshandeh, Hooman; Rafiee, Farnaz; Matin, Samira; Baghizadeh, Elahe; Rezaeifar, Parisa; Jamalkhani, Sepehr; Tahamtan, Ooria; Sharif-Kashani, Babak; Beigmohammadi, Mohammad Taghi; Farrokhpour, Mohsen; Sezavar, Seyed Hashem; Payandemehr, Pooya; Dabbagh, Ali; Gohari Moghadam, Keivan; Khalili, Hossein; Yadollahzadeh, Mahdi; Riahi, Taghi; Abedini, Atefeh; Lookzadeh, Somayeh; Rahmani, Hamid; Zoghi, Elnaz; Mohammadi, Keyhan; Sadeghipour, Pardis; Abri, Homa; Tabrizi, Sanaz; Mousavian, Seyed Masoud; Shahmirzaei, Shaghayegh; Amin, Ahmad; Mohebbi, Bahram; Parhizgar, Seyed Ehsan; Aliannejad, Rasoul; Eslami, Vahid; Kashefizadeh, Alireza; Dobesh, Paul; Kakavand, Hessam; Hosseini, Seyed Hossein; Shafaghi, Shadi; Fattah Ghazi, Samrand; Najafi, Atabak; Jiménez, David; Gupta, Aakriti; Madhavan, Mahesh V; Sethi, Sanjum; Parikh, Sahil A; Monreal, Manuel; Hadavand, Naser; Hajighasemi, Alireza; Maleki, Majid; Sadeghian, Saeed; Piazza, Gregory; Kirtane, Ajay J; Van Tassell, Benjamin W; Stone, Gregg W; Lip, Gregory Yh; Krumholz, Harlan; Goldhaber, Samuel Z; Sadeghipour, Parham

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.