دورية أكاديمية
Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.
| العنوان: | Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial. |
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| المؤلفون: | Berger JS; NYU Grossman School of Medicine, New York, New York., Kornblith LZ; University of California, San Francisco., Gong MN; Albert Einstein College of Medicine, Bronx, New York., Reynolds HR; NYU Grossman School of Medicine, New York, New York., Cushman M; College of Medicine, University of Vermont, Burlington., Cheng Y; University of Pittsburgh, Pittsburgh, Pennsylvania., McVerry BJ; University of Pittsburgh, Pittsburgh, Pennsylvania., Kim KS; University of Illinois, Chicago., Lopes RD; Duke University Medical Center, Durham, North Carolina., Atassi B; OSF Little Company of Mary Medical Center, Evergreen Park, Illinois., Berry S; Berry Consultants LLC, Austin, Texas., Bochicchio G; School of Medicine, Washington University, St Louis, Missouri., de Oliveira Antunes M; Hospital Universitario São Francisco de Assis, São Paulo, Brazil., Farkouh ME; Peter Munk Cardiac Centre, Toronto, Ontario, Canada., Greenstein Y; New Jersey Medical School, Rutgers University, Newark., Hade EM; NYU Grossman School of Medicine, New York, New York., Hudock K; University of Cincinnati Medical Center, Cincinnati, Ohio., Hyzy R; University of Michigan, Ann Arbor., Khatri P; University of Cincinnati Medical Center, Cincinnati, Ohio., Kindzelski A; National Heart, Lung, and Blood Institute, Bethesda, Maryland., Kirwan BA; Socar Research SA, Nyon, Switzerland., Baumann Kreuziger L; Versity Blood Research Institute, Milwaukee, Wisconsin., Lawler PR; Peter Munk Cardiac Centre, Toronto, Ontario, Canada., Leifer E; National Heart, Lung, and Blood Institute, Bethesda, Maryland., Lopez-Sendon Moreno J; Hospital Universitario Ramon Y Cajal, Madrid, Spain., Lopez-Sendon J; Hospital Universitario La Paz, Madrid, Spain., Luther JF; University of Pittsburgh, Pittsburgh, Pennsylvania., Nigro Maia L; Fundação Faculdade Regional De Medicina De São José Do Rio Preto, São José do Rio Preto, Brazil., Quigley J; University of Illinois, Chicago., Sherwin R; Wayne State University, Detroit, Michigan., Wahid L; Duke University Hospital, Durham, North Carolina., Wilson J; Stanford University Medical Center, Stanford, California., Hochman JS; NYU Grossman School of Medicine, New York, New York., Neal MD; University of Pittsburgh, Pittsburgh, Pennsylvania. |
| مؤلفون مشاركون: | ACTIV-4a Investigators |
| المصدر: | JAMA [JAMA] 2022 Jan 18; Vol. 327 (3), pp. 227-236. |
| نوع المنشور: | Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago : American Medical Association, 1960- |
| مواضيع طبية MeSH: | Inpatients* , COVID-19 Drug Treatment*, Anticoagulants/*administration & dosage , Heparin/*administration & dosage , Purinergic P2Y Receptor Antagonists/*administration & dosage, Aged ; Aged, 80 and over ; Anticoagulants/adverse effects ; COVID-19/blood ; COVID-19/mortality ; Clopidogrel/administration & dosage ; Clopidogrel/adverse effects ; Comorbidity ; Extracorporeal Membrane Oxygenation/statistics & numerical data ; Female ; Hemorrhage/chemically induced ; Heparin/adverse effects ; Hospital Mortality ; Humans ; Male ; Medical Futility ; Middle Aged ; Outcome Assessment, Health Care ; Oxygen Inhalation Therapy/statistics & numerical data ; Platelet Activation/drug effects ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/adverse effects ; Purinergic P2Y Receptor Antagonists/adverse effects ; Receptors, Purinergic P2Y12 ; Respiration, Artificial/statistics & numerical data ; Thrombosis/epidemiology ; Ticagrelor/administration & dosage ; Ticagrelor/adverse effects ; Time Factors ; Treatment Outcome |
| مستخلص: | Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774. |
| التعليقات: | Comment in: JAMA. 2022 Jan 18;327(3):223-224. (PMID: 35040901) |
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| معلومات مُعتمدة: | K23 HL133495 United States HL NHLBI NIH HHS; OT2 HL156812 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Investigator: J Newman; M Geraci; A Maggioni; H Kamel; EC Goligher; R Zarychanski; BM Everett; S van Diepen; G Le Gal; DM Siegal; JP Galanaud; S Hegde; Y Kim; NS Rost; AB Singhal; A Contreras; S Mavromichalis; E Iturrate; M Gilsenan; A Naumova; A Roberts; J Levine; CM Leeper; DC Angus; M Martinez; J Schreiber; J Froess; CE Stehle; AS Vadlamudi; F Sciurba; A Morris; E Music; S de Brouwer; E Perrin; C Gombault; S Bula; M Nelson; C Daelemans; L Paraz; MA Detry; A McGlothlin; M Quintana; A Crawford; D Sin; E Diene; E Gwiszcz; I Hogan; A Holden; N Ringwood; L Fitzgerald; H Morin; B Nunez-Garcia; AE Kornblith; CM Hendrickson; D Lee; V Nguyen; I Shelley; S Broaddrick; N Atal; DT Huang; R Wunderly; M Buxton; T Roberts; K Linstrum; A McNamara; A Weissman; D Barbee; E Berryman; J Frasure; A Sulken; JN Ianof; L Mazza; J Morata; CM Cafarella; MA Suiama; D de Lima Franco; J Escobedo; A Martinez; P Ohara; D Assis; C Manzalini; S Corsi; G Campo; P Prieto; R Prieto; S Garg; R Fonseca; S Reese; O Mohammed; R Dolor; TL Ortel; C Wolfe; M Plump; R Nair; W Nkemdirim; JT Chen; B Galen; A Moskowitz; N Keller; E Yuriditsky; J Horowitz; A Hindenburg; T Chkhikvadze; L Bassoli; T Costa; JL López-Sendón Moreno; F Rodriguez Jorge; S García Madrona; R Morillo Guerrero; M Alpañes Buesa; R Nieto Royo; R Besse Diaz; S Diz Fariña; A Gonzalez García; O da Silva Júnior; C Pradela; C Jorge; M Buka; O Costa; D Frassatto; J Vieira; P Dutra; L Moreira; N da Silva; N Prado; A Martins; A Centurione; A de Matos Soeiro; PR Avancini Caramori; N Coppola; M Contoli; E Lopez-de-Sa; F Worner; A López-Bernús; JR Gonzalez Juanatey; J Peteiro; S Gandotra; V Krishnan; R Widmer; L Satterwhite; A Macchiavelli; N Hanna; H Patel; R Lyubarova; E Gashi; A Alvaro; S Pan; S Vallurupalli; N Iovine; R Nair; A Jathavedam; A Shah; A Duggal; A Khan; MA Matthay; ME Prekker; G Lim; S Moore; TW Costantini; ME Kutcher; B Joseph; M Bromberg; MB Effron; A Pishko; JP Sheehan; M Gaddh; K Rezai; JG Latorre; C Liang; Z Ajani; S Guo; M Whitson |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04505774 |
| المشرفين على المادة: | 0 (Anticoagulants) 0 (P2RY12 protein, human) 0 (Platelet Aggregation Inhibitors) 0 (Purinergic P2Y Receptor Antagonists) 0 (Receptors, Purinergic P2Y12) 9005-49-6 (Heparin) A74586SNO7 (Clopidogrel) GLH0314RVC (Ticagrelor) |
| تواريخ الأحداث: | Date Created: 20220118 Date Completed: 20220127 Latest Revision: 20231117 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8767444 |
| DOI: | 10.1001/jama.2021.23605 |
| PMID: | 35040887 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-3598 |
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| DOI: | 10.1001/jama.2021.23605 |