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
Por:
Sadeghipour, P, Talasaz, AH, Rashidi, F, Sharif-Kashani, B, Beigmohammadi, MT, Farrokhpour, M, Sezavar, SH, Payandemehr, P, Dabbagh, A, Moghadam, KG, Jamalkhani, S, Khalili, H, Yadollahzadeh, M, Riahi, T, Rezaeifar, P, Tahamtan, O, Matin, S, Abedini, A, Lookzadeh, S, Rahmani, H, Zoghi, E, Mohammadi, K, Sadeghipour, P, Abri, H, Tabrizi, S, Mousavian, SM, Shahmirzaei, S, Bakhshandeh, H, Amin, A, Rafiee, F, Baghizadeh, E, Mohebbi, B, Parhizgar, SE, Aliannejad, R, Eslami, V, Kashefizadeh, A, Kakavand, H, Hosseini, SH, Shafaghi, S, Ghazi, SF, Najafi, A, Jimenez, D, Gupta, A, Madhavan, MV, Sethi, SS, Parikh, SA, Monreal, M, Hadavand, N, Hajighasemi, A, Maleki, M, Sadeghian, S, Piazza, G, Kirtane, AJ, Van Tassell, BW, Dobesh, PP, Stone, GW, Lip, GYH, Krumholz, HM, Goldhaber, SZ and Bikdeli, B
Publicada:
27 abr 2021
Ahead of Print:
1 mar 2021
Resumen:
Importance Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants Multicenter randomized trial with a 2 x 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 x10(3)/mu L). All outcomes were blindly adjudicated. Results Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -infinity to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19.
Question What are the effects of intermediate-dose compared with standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit (ICU)? Findings In this randomized clinical trial that included 562 patients with COVID-19 admitted to the ICU, the primary outcome (a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days) occurred in 45.7% of patients in the intermediate-dose prophylactic anticoagulation group and 44.1% of patients in the standard-dose prophylactic anticoagulation group, a difference that was not statistically significant (odds ratio, 1.06). Meaning The results do not support routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients with COVID-19 admitted to the ICU.
This randomized trial compares the effect of intermediate-dose vs standard prophylactic enoxaparin on a composite outcome of acute venous thromboembolism (VTE), arterial thrombosis, need for extracorporeal membrane oxygenation (ECMO), and all-cause mortality within 30 days among patients with COVID-19 admitted to the ICU.
Filiaciones:
Sadeghipour, P:
Iran Univ Med Sci, Cardiovasc Intervent Res Ctr, Rajaie Cardiovasc Med & Res Ctr, Vali Asr Ave,Niyayesh Blvd, Tehran 1996911101, Iran
Iran Univ Med Sci, Clin Trial Ctr, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Iran Univ Med Sci, Firouzgar Hosp, Dept Internal Med, Tehran, Iran
Talasaz, AH:
Univ Tehran Med Sci, Tehran Heart Ctr, Tehran, Iran
Rashidi, F:
TB & Lung Dis Res Ctr, Tabriz, Iran
Sharif-Kashani, B:
Shahid Beheshti Univ Med Sci, Natl Res Inst TB & Lung Dis NRITLD, Tobacoo Prevent & Control Res Ctr, Tehran, Iran
Shahid Beheshti Univ Med Sci, Natl Res Inst TB & Lung Dis NRITLD, Dept Cardiol, Lung Transplantat Res Ctr, Tehran, Iran
Beigmohammadi, MT:
Univ Tehran Med Sci, Imam Khomeini Hosp Complex, Anesthesiol & Intens Care, Tehran, Iran
Farrokhpour, M:
Iran Univ Med Sci, Firouzgar Hosp, Dept Internal Med, Tehran, Iran
Sezavar, SH:
Iran Univ Med Sci, Inst Endocrinol & Metab, Res Ctr Prevent Cardiovasc Dis, Tehran, Iran
Payandemehr, P:
Univ Tehran Med Sci, Sina Hosp, Tehran, Iran
Dabbagh, A:
Shahid Beheshti Univ Med Sci, Sch Med Anesthesiol, Dept Anesthesiol, Res Ctr,Shahid Modarres Hosp, Tehran, Iran
Moghadam, KG:
Shariati Hosp, Sch Med, Dept Internal Med, Tehran, Iran
Jamalkhani, S:
Iran Univ Med Sci, Student Res Comm, Tehran, Iran
Khalili, H:
Univ Tehran Med Sci, Imam Khomeini Hosp Complex, Dept Pharmacotherapy, Tehran, Iran
Yadollahzadeh, M:
Iran Univ Med Sci, Firouzgar Hosp, Dept Internal Med, Tehran, Iran
Riahi, T:
Iran Univ Med Sci, Rasoul e Akram Hosp, Tehran, Iran
Rezaeifar, P:
TB & Lung Dis Res Ctr, Tabriz, Iran
Tahamtan, O:
TB & Lung Dis Res Ctr, Tabriz, Iran
Matin, S:
TB & Lung Dis Res Ctr, Tabriz, Iran
Abedini, A:
Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Chron Resp Dis Res Ctr, Tehran, Iran
Lookzadeh, S:
Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Chron Resp Dis Res Ctr, Tehran, Iran
Rahmani, H:
Kermanshah Univ Med Sci, Dept Pharmacotherapy, Fac Pharm, Kermanshah, Iran
Zoghi, E:
Univ Tehran Med Sci, Sch Pharm, Tehran, Iran
Mohammadi, K:
Univ Tehran Med Sci, Sch Pharm, Tehran, Iran
Sadeghipour, P:
Iran Univ Med Sci, Cardiovasc Intervent Res Ctr, Rajaie Cardiovasc Med & Res Ctr, Vali Asr Ave,Niyayesh Blvd, Tehran 1996911101, Iran
Iran Univ Med Sci, Clin Trial Ctr, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Iran Univ Med Sci, Firouzgar Hosp, Dept Internal Med, Tehran, Iran
Abri, H:
Iran Univ Med Sci, Firouzgar Hosp, Dept Internal Med, Tehran, Iran
Tabrizi, S:
Iran Univ Med Sci, Rasoul e Akram Hosp, Tehran, Iran
Mousavian, SM:
Iran Univ Med Sci, Rasoul e Akram Hosp, Tehran, Iran
Shahmirzaei, S:
Univ Tehran Med Sci, Sina Hosp, Tehran, Iran
Bakhshandeh, H:
Iran Univ Med Sci, Clin Trial Ctr, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Amin, A:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Rafiee, F:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Baghizadeh, E:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Mohebbi, B:
Iran Univ Med Sci, Cardiovasc Intervent Res Ctr, Rajaie Cardiovasc Med & Res Ctr, Vali Asr Ave,Niyayesh Blvd, Tehran 1996911101, Iran
Parhizgar, SE:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Aliannejad, R:
Shariati Hosp, Sch Med, Dept Pulm & Crit Care, Tehran, Iran
Univ Tehran Med Sci, Adv Thorac Res Ctr, Tehran, Iran
Eslami, V:
Shahid Beheshti Univ Med Sci, Cardiovasc Res Ctr, Tehran, Iran
Kashefizadeh, A:
Shahid Beheshti Univ Med Sci, Shahid Dr Labbafinejad Hosp, Tehran, Iran
Kakavand, H:
Univ Tehran Med Sci, Sch Pharm, Tehran, Iran
Hosseini, SH:
Univ Tehran Med Sci, Sch Pharm, Tehran, Iran
Shafaghi, S:
Shahid Beheshti Univ Med Sci, Natl Res Inst TB & Lung Dis NRITLD, Dept Cardiol, Lung Transplantat Res Ctr, Tehran, Iran
Ghazi, SF:
Univ Tehran Med Sci, Imam Khomeini Hosp Complex, Anesthesiol & Intens Care, Tehran, Iran
Najafi, A:
Univ Tehran Med Sci, Sina Hosp, Tehran, Iran
Jimenez, D:
Hosp Ramon Y Cajal IRYCIS, Resp Dept, Madrid, Spain
Univ Alcala IRYCIS, Med Dept, Madrid, Spain
CIBER Enfermedades Resp CIBERES, Madrid, Spain
Gupta, A:
Cardiovasc Res Fdn CRF, New York, NY USA
Columbia Univ, Irving Med Ctr, NewYork Presbyterian Hosp, Div Cardiol, New York, NY USA
Yale YNHH Ctr Outcomes Res & Evaluat, New Haven, CT USA
Madhavan, MV:
Cardiovasc Res Fdn CRF, New York, NY USA
Columbia Univ, Irving Med Ctr, NewYork Presbyterian Hosp, Div Cardiol, New York, NY USA
Sethi, SS:
Cardiovasc Res Fdn CRF, New York, NY USA
Columbia Univ, Irving Med Ctr, NewYork Presbyterian Hosp, Div Cardiol, New York, NY USA
Parikh, SA:
Cardiovasc Res Fdn CRF, New York, NY USA
Columbia Univ, Irving Med Ctr, NewYork Presbyterian Hosp, Div Cardiol, New York, NY USA
:
Hosp Badalona Germans Trias & Pujol, Dept Internal Med, Barcelona, Spain
Univ Catolica Murcia, Murcia, Spain
Hadavand, N:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Hajighasemi, A:
Univ Tehran Med Sci, Tehran Heart Ctr, Tehran, Iran
Maleki, M:
Iran Univ Med Sci, Rajaie Cardiovasc Med & Res Ctr, Tehran, Iran
Sadeghian, S:
Univ Tehran Med Sci, Tehran Heart Ctr, Tehran, Iran
Piazza, G:
Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Med Div, Boston, MA 02115 USA
Kirtane, AJ:
Cardiovasc Res Fdn CRF, New York, NY USA
Columbia Univ, Irving Med Ctr, NewYork Presbyterian Hosp, Div Cardiol, New York, NY USA
Van Tassell, BW:
Virginia Commonwealth Univ, Sch Pharm, Dept Pharmacotherapy & Outcome Sci, Richmond, VA USA
Virginia Commonwealth Univ, Sch Pharm, Dept Internal Med, Pauley Heart Ctr,Div Cardiol, Richmond, VA USA
Dobesh, PP:
Univ Nebraska Med Ctr, Coll Pharm, Omaha, NE USA
Stone, GW:
Cardiovasc Res Fdn CRF, New York, NY USA
Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA
Lip, GYH:
Univ Liverpool, Liverpool Ctr Cardiovasc Sci, Liverpool, Merseyside, England
Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England
Aalborg Univ, Aalborg, Denmark
Krumholz, HM:
Yale YNHH Ctr Outcomes Res & Evaluat, New Haven, CT USA
Yale Sch Med, Sect Cardiovasc Med, Dept Internal Med, New Haven, CT USA
Yale Sch Publ Hlth, Dept Hlth Policy & Adm, New Haven, CT USA
Goldhaber, SZ:
Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Med Div, Boston, MA 02115 USA
Bikdeli, B:
Cardiovasc Res Fdn CRF, New York, NY USA
Yale YNHH Ctr Outcomes Res & Evaluat, New Haven, CT USA
Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Med Div, Boston, MA 02115 USA
Bronze, Green Published
|