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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalThrombosis and Haemostasis
Volume122
Issue number1
DOIs
StatePublished - Jan 1 2021

Keywords

  • COVID-19
  • anticoagulation
  • enoxaparin
  • heparin
  • trial

ASJC Scopus subject areas

  • Hematology

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