Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Derde Lennie, Gordon Anthony C, Mouncey Paul R, Al-Beidh Farah, Rowan Kathryn M, Nichol Alistair D, Arabi Yaseen M, Annane Djillali, Beane Abigail, Beasley Richard, Bonten Marc J M, Bradbury Charlotte A, Brunkhorst Frank M, Buzgau Adrian, Buxton Meredith, Cheng Allen C, Cooper Nicola, Cove Matthew, Cremer Olaf L, Detry Michelle A, Duffy Eamon J, Estcourt Lise J, Fitzgerald Mark, Galea James, Goossens Herman, Haniffa Rashan, Hills Thomas E, Huang David T, Ichihara Nao, King Andrew, Lamontagne François, Lawler Patrick R, Leavis Helen L, Lewis Roger J, Litton Edward, Marshall John C, Mayr Florian B, McAuley Daniel F, McGlothlin Anna, McGuinness Shay P, McVerry Bryan J, Morpeth Susan C, Murthy Srinivas, Netea Mihai G, Ogungbenro Kayode, Orr Katrina, Parke Rachael L, Parker Jane C, Patanwala Asad E, Pettila Ville, Reyes Luis Felipe, Saito Hiroki, Santos Marlene S, Saunders Christina T, Seymour Christopher W, Shankar-Hari Manu, Sligl Wendy I, Turgeon Alexis F, Turner Anne M, Tong Steven Y C, Vaara Suvi, Youngstein Taryn, Zarychanski Ryan, Green Cameron, Higgins Alisa M, McArthur Colin J, Berry Lindsay R, Lorenzi Elizabeth, Berry Scott, Webb Steve A, Angus Derek C, van de Veerdonk Frank L
Аннотация
METHODS: We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients. In this ongoing, adaptive platform trial in 133 sites in 9 countries, we randomly assigned patients with allocation ratios dependent on the number of interventions available at each site. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21 in survivors. The trial used a Bayesian statistical model with predefined triggers for superiority, inferiority, efficacy, equivalence or futility.
RESULTS: Of 2274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (IQR -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted ORs were 1.46 (95% credible intervals (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) and 0.99 (95% CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra relative to control, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared with control. All treatments appeared safe.
CONCLUSIONS: In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death. Anakinra is not effective in this population.
TRIAL REGISTRATION NUMBER: NCT02735707.