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.
Autor: | Sadeghipour P; Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran., Talasaz AH; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Rashidi F; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Sharif-Kashani B; Tobacoo Prevention and control Research center, National Research institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Lung Transplantation Research Center, Department of Cardiology, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran., Beigmohammadi MT; Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Farrokhpour M; Firouzgar hospital, Department of internal medicine, Iran University of Medical Sciences, Tehran, Iran., Sezavar SH; Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran., Payandemehr P; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Dabbagh A; Department of Anesthesiology, School of Medicine Anesthesiology Research Center Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Moghadam KG; School of Medicine, Department of Internal Medicine, Shariati Hospital, Tehran, Iran., Jamalkhani S; Student Research Committee, Iran University of Medical Sciences, Tehran, Iran., Khalili H; Department of Pharmacotherapy, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Yadollahzadeh M; Firouzgar hospital, Department of internal medicine, Iran University of Medical Sciences, Tehran, Iran., Riahi T; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Rezaeifar P; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Tahamtan O; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Matin S; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Abedini A; Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Lookzadeh S; Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Rahmani H; Department of Pharmacotherapy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran., Zoghi E; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Mohammadi K; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Sadeghipour P; Firouzgar hospital, Department of internal medicine, Iran University of Medical Sciences, Tehran, Iran., Abri H; Firouzgar hospital, Department of internal medicine, Iran University of Medical Sciences, Tehran, Iran., Tabrizi S; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Mousavian SM; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Shahmirzaei S; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Bakhshandeh H; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Amin A; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Rafiee F; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Baghizadeh E; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Mohebbi B; Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran., Parhizgar SE; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Aliannejad R; School of Medicine, Department of Pulmonary and Critical Care, Shariati Hospital, Tehran, Iran.; Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran., Eslami V; Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Kashefizadeh A; Shahid Dr Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Kakavand H; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Hosseini SH; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Shafaghi S; Lung Transplantation Research Center, Department of Cardiology, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran., Ghazi SF; Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Najafi A; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Jimenez D; Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain.; Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain.; CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain., Gupta A; Cardiovascular Research Foundation (CRF), New York, New York.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York.; Yale/YNHH Center for Outcomes Research & Evaluation, New Haven, Connecticut., Madhavan MV; Cardiovascular Research Foundation (CRF), New York, New York.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York., Sethi SS; Cardiovascular Research Foundation (CRF), New York, New York.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York., Parikh SA; Cardiovascular Research Foundation (CRF), New York, New York.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York., Monreal M; Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Universidad Católica de Murcia, Murcia, Spain., Hadavand N; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Hajighasemi A; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Maleki M; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical sciences, Tehran, Iran., Sadeghian S; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Piazza G; Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Kirtane AJ; Cardiovascular Research Foundation (CRF), New York, New York.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York., Van Tassell BW; School of Pharmacy, Department of Pharmacotherapy and Outcome Science, Virginia Commonwealth University, Richmond, Virginia.; School of Pharmacy, Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia., Dobesh PP; College of Pharmacy, University of Nebraska Medical Center, Omaha., Stone GW; Cardiovascular Research Foundation (CRF), New York, New York.; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Lip GYH; Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.; Aalborg University, Aalborg, Denmark., Krumholz HM; Yale/YNHH Center for Outcomes Research & Evaluation, New Haven, Connecticut.; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.; Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut., Goldhaber SZ; Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Bikdeli B; Cardiovascular Research Foundation (CRF), New York, New York.; Yale/YNHH Center for Outcomes Research & Evaluation, New Haven, Connecticut.; Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. |
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Jazyk: | angličtina |
Zdroj: | JAMA [JAMA] 2021 Apr 27; Vol. 325 (16), pp. 1620-1630. |
DOI: | 10.1001/jama.2021.4152 |
Abstrakt: | 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 × 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 ×103/µL). 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, -∞ 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. |
Databáze: | MEDLINE |
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