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10.1001/jama.2021.4152

http://scihub22266oqcxt.onion/10.1001/jama.2021.4152
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suck abstract from ncbi


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pmid33734299      JAMA 2021 ; 325 (16): 1620-1630
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  • 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 #MMPMID33734299
  • 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; Bikdeli B
  • JAMA 2021[Apr]; 325 (16): 1620-1630 PMID33734299show ga
  • 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 x103/microL). 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04486508.
  • |*Extracorporeal Membrane Oxygenation[MESH]
  • |Aged[MESH]
  • |Anticoagulants/*administration & dosage/adverse effects[MESH]
  • |COVID-19/*complications/mortality[MESH]
  • |Drug Administration Schedule[MESH]
  • |Enoxaparin/*administration & dosage/adverse effects[MESH]
  • |Female[MESH]
  • |Hemorrhage/chemically induced[MESH]
  • |Hospitalization[MESH]
  • |Humans[MESH]
  • |Intensive Care Units[MESH]
  • |Iran[MESH]
  • |Length of Stay/statistics & numerical data[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Odds Ratio[MESH]
  • |Outcome Assessment, Health Care[MESH]
  • |Oxygen Inhalation Therapy/*methods[MESH]
  • |Pulmonary Embolism/epidemiology[MESH]
  • |Thrombocytopenia/chemically induced[MESH]
  • |Thrombosis/etiology/mortality/*prevention & control[MESH]
  • |Treatment Outcome[MESH]


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