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Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial.
Eikelboom, John W; Jolly, Sanjit S; Belley-Cote, Emilie P; Whitlock, Richard P; Rangarajan, Sumathy; Xu, Lizhen; Heenan, Laura; Bangdiwala, Shrikant I; Luz Diaz, Maria; Diaz, Rafael; Yusufali, Afzalhussein; Kumar Sharma, Sanjib; Tarhuni, Wadea M; Hassany, Mohamed; Avezum, Alvaro; Harper, William; Wasserman, Sean; Almas, Aysha; Drapkina, Oxana; Felix, Camilo; Lopes, Renato D; Berwanger, Otavio; Lopez-Jaramillo, Patricio; Anand, Sonia S; Bosch, Jackie; Choudhri, Shurjeel; Farkouh, Michael E; Loeb, Mark; Yusuf, Salim.
  • Eikelboom JW; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: eikelbj@mcmaster.ca.
  • Jolly SS; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Belley-Cote EP; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Whitlock RP; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
  • Rangarajan S; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada.
  • Xu L; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada.
  • Heenan L; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada.
  • Bangdiwala SI; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada.
  • Luz Diaz M; Estudios Clínicos Latino América, Instituto Cardiovascular de Rosario, Rosario, Argentina.
  • Diaz R; Estudios Clínicos Latino América, Instituto Cardiovascular de Rosario, Rosario, Argentina.
  • Yusufali A; Hatta Hospital, Dubai Medical College, Dubai Health Authority, Dubai, United Arab Emirates.
  • Kumar Sharma S; BP Koirala Institute of Health Sciences, Dharan, Nepal.
  • Tarhuni WM; Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada; Department of Medicine, Western University, Clinical Skills Building London, ON, Canada; Windsor Cardiac Centre, Windsor, ON, Canada.
  • Hassany M; National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
  • Avezum A; International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
  • Harper W; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada.
  • Wasserman S; Wellcome Centre for Infectious Diseases Research in Africa, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Division of Infectious Diseases and HIV Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
  • Almas A; Section of Internal Medicine, Department of Medicine, Aga Khan University, Karachi, Pakistan.
  • Drapkina O; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.
  • Felix C; Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Ecuador.
  • Lopes RD; Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute, NC, USA.
  • Berwanger O; Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Lopez-Jaramillo P; Masira Research Institute, Medical School, Universidad de Santander, Bucaramanga, Colombia.
  • Anand SS; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Bosch J; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
  • Choudhri S; Bayer, Medical & Scientific Affairs, Mississauga, ON, Canada.
  • Farkouh ME; Peter Munk Cardiac Centre, University of Toronto, Toronto, ON, Canada.
  • Loeb M; Departments of Pathology and Molecular Medicine and Health Evidence Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Yusuf S; Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Lancet Respir Med ; 10(12): 1169-1177, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2062044
ABSTRACT

BACKGROUND:

COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19.

METHODS:

The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (11) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (11) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www. CLINICALTRIALS gov, NCT04324463 and is ongoing.

FINDINGS:

Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio [HR] 1·04, 95% CI 0·90-1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78-1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 [6·7%] of 1304 vs 90 [6·9%] of 1307) or with rivaroxaban and aspirin versus control groups (85 [8·0%] vs 91 [8·6%]). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug.

INTERPRETATION:

Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death.

FUNDING:

Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, Thistledown Foundation. TRANSLATIONS For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.
Тема - темы

Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Rivaroxaban / COVID-19 Drug Treatment Тип исследования: Когортное исследование / Экспериментальные исследования / Прогностическое исследование / Рандомизированные контролируемые испытания Темы: Вакцина Пределы темы: Подростки / Взрослые / Люди Страна как тема: Северная Америка Язык: английский Журнал: Lancet Respir Med Год: 2022 Тип: Статья

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Rivaroxaban / COVID-19 Drug Treatment Тип исследования: Когортное исследование / Экспериментальные исследования / Прогностическое исследование / Рандомизированные контролируемые испытания Темы: Вакцина Пределы темы: Подростки / Взрослые / Люди Страна как тема: Северная Америка Язык: английский Журнал: Lancet Respir Med Год: 2022 Тип: Статья