Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial
Authors: Bikdeli Behnood , Talasaz Azita H. , Rashidi Farid , Bakhshandeh Hooman , Rafiee Farnaz , Rezaeifar Parisa , Baghizadeh Elahe , Matin Samira , Jamalkhani Sepehr , Tahamtan Ouria , Sharif-Kashani Babak , Beigmohammadi Mohammad Taghi , Farrokhpour Mohsen , Sezavar Seyed Hashem , Payandemehr Pooya , Dabbagh Ali , Moghadam Keivan Gohari , 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 P. , Kakavand Hessam , Hosseini Seyed Hossein , Shafaghi Shadi , Ghazi Samrand Fattah , Najafi Atabak , Jimenez David , Gupta Aakriti , Madhavan Mahesh V. , Sethi Sanjum S. , 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 Y. H. , Krumholz Harlan M. , Goldhaber Samuel Z. , Sadeghipour Parham 
Published: April 2021

Abstract
Background Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown.
Methods This article 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). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45–5.06). 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).
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.