[저자] Cathrine Axfors, Perrine Janiaud, Andreas M. Schmitt, Janneke van’t Hooft, Emily R. Smith, Noah A. Haber, Akin Abayomi, Manal Abduljalil, Abdulkarim Abdulrahman, Yeny Acosta-Ampudia, Manuela Aguilar-Guisado, Farah Al-Beidh, Marissa M. Alejandria, Rachelle N. Alfonso, Mohammad Ali, Manaf AlQahtani, Alaa AlZamrooni, Juan-Manuel Anaya, Mark Angelo C. Ang, Ismael F. Aomar, Luis E. Argumanis, Alexander Averyanov, Vladimir P. Baklaushev, Olga Balionis, Thomas Benfield, Scott Berry, Nadia Birocco, Lynn B. Bonifacio, Asha C. Bowen, Abbie Bown, Carlos Cabello-Gutierrez, Bernardo Camacho, Adrian Camacho-Ortiz, Sally Campbell-Lee, Damon H. Cao, Ana Cardesa, Jose M. Carnate, German Jr. J. Castillo, Rossana Cavallo, Fazle R. Chowdhury, Forhad U. H. Chowdhury, Giovannino Ciccone, Antonella Cingolani, Fresthel Monica M. Climacosa, Veerle Compernolle, Carlo Francisco N. Cortez, Abel Costa Neto, Sergio D’Antico, James Daly, Franca Danielle, Joshua S. Davis, Francesco Giuseppe De Rosa, Justin T. Denholm, Claudia M. Denkinger, Daniel Desmecht, Juan C. Díaz-Coronado, Juan A. Díaz Ponce-Medrano, Anne-Françoise Donneau, Teresita E. Dumagay, Susanna Dunachie, Cecile C. Dungog, Olufemi Erinoso, Ivy Mae S. Escasa, Lise J. Estcourt, Amy Evans, Agnes L. M. Evasan, Christian J. Fareli, Veronica Fernandez-Sanchez, Claudia Galassi, Juan E. Gallo, Patricia J. Garcia, Patricia L. Garcia, Jesus A. Garcia, Mutien Garigliany, Elvira Garza-Gonzalez, Deonne Thaddeus V. Gauiran, Paula A. Gaviria García, Jose-Antonio Giron-Gonzalez, David Gómez-Almaguer, Anthony C. Gordon, André Gothot, Jeser Santiago Grass Guaqueta, Cameron Green, David Grimaldi, Naomi E. Hammond, Heli Harvala, Francisco M. Heralde, Jesica Herrick, Alisa M. Higgins, Thomas E. Hills, Jennifer Hines, Karin Holm, Ashraful Hoque, Eric Hoste, Jose M. Ignacio, Alexander V. Ivanov, Maike Janssen, Jeffrey H. Jennings, Vivekanand Jha, Ruby Anne N. King, Jens Kjeldsen-Kragh, Paul Klenerman, Aditya Kotecha, Fiorella Krapp, Luciana Labanca, Emma Laing, Mona Landin-Olsson, Pierre-François Laterre, Lyn-Li Lim, Jodor Lim, Oskar Ljungquist, Jorge M. Llaca-Díaz, Concepción López-Robles, Salvador López-Cárdenas, Ileana Lopez-Plaza, Josephine Anne C. Lucero, Maria Lundgren, Juan Macías, Sandy C. Maganito, Anna Flor G. Malundo, Rubén D. Manrique, Paola M. Manzini, Miguel Marcos, Ignacio Marquez, Francisco Javier Martínez-Marcos, Ana M. Mata, Colin J. McArthur, Zoe K. McQuilten, Bryan J. McVerry, David K. Menon, Geert Meyfroidt, Ma. Angelina L. Mirasol, Benoît Misset, James S. Molton, Alric V. Mondragon, Diana M. Monsalve, Parastoo Moradi Choghakabodi, Susan C. Morpeth, Paul R. Mouncey, Michel Moutschen, Carsten Müller-Tidow, Erin Murphy, Tome Najdovski, Alistair D. Nichol, Henrik Nielsen, Richard M. Novak, Matthew V. N. O’Sullivan, Julian Olalla, Akin Osibogun, Bodunrin Osikomaiya, Salvador Oyonarte, Juan M. Pardo-Oviedo, Mahesh C. Patel, David L. Paterson, Carlos A. Peña-Perez, Angel A. Perez-Calatayud, Eduardo Pérez-Alba, Anastasia Perkina, Naomi Perry, Mandana Pouladzadeh, Inmaculada Poyato, David J. Price, Anne Kristine H. Quero, Md. M. Rahman, Md. S. Rahman, Mayur Ramesh, Carolina Ramírez-Santana, Magnus Rasmussen, Megan A. Rees, Eduardo Rego, Jason A. Roberts, David J. Roberts, Yhojan Rodríguez, Jesús Rodríguez-Baño, Benjamin A. Rogers, Manuel Rojas, Alberto Romero, Kathryn M. Rowan, Fabio Saccona, Mehdi Safdarian, Maria Clariza M. Santos, Joe Sasadeusz, Gitana Scozzari, Manu Shankar-Hari, Gorav Sharma, Thomas Snelling, Alonso Soto, Pedrito Y. Tagayuna, Amy Tang, Geneva Tatem, Luciana Teofili, Steven Y. C. Tong, Alexis F. Turgeon, Januario D. Veloso, Balasubramanian Venkatesh, Yanet Ventura-Enriquez, Steve A. Webb, Lothar Wiese, Christian Wikén, Erica M. Wood, Gaukhar M. Yusubalieva, Kai Zacharowski, Ryan Zarychanski, Nina Khanna, David Moher, Steven N. Goodman, John P. A. Ioannidis, Lars G. Hemkens
[Category] MERS, SARS, 비임상, 임상, 진단,
[Article Type] Meta-Analysis
[Source] PMC
Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I 2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06829-7.
All Keywords
【저자키워드】 COVID-19, convalescent plasma, Meta-analysis, SARS-CoV-2, breath, 【초록키워드】 Treatment, convalescent plasma, Meta-analysis, randomized clinical trial, Trial, intensive care, clinical trials, systematic review, risk, database, heterogeneity, clinical, weight, Patient, plasma, WHO, Placebo, registry, randomized clinical trials, mortality data, patients, trials, RECOVERY trial, COVID-19 patients, Evidence, risk ratio, open, Patient care, randomized trials, supplementary material, email, chance, all-cause mortality, control patients, WHO International Clinical Trials Registry Platform, Registered, investigators, investigator, treat, convalescent plasma treatment, Open Science Framework, random effect, benefit, Result, enrolled, died, investigated, provided, searched, hospitalized patient, did not reduce, clinical trial registry, ongoing trial, patients with COVID-19, 【제목키워드】 randomized clinical trial, Mortality, systematic review,
배경 회복기 혈장은 COVID-19 치료에 널리 사용되어 왔으며 수많은 무작위 임상 시험에서 조사 중이지만 결과는 소수의 시험에서만 공개적으로 제공됩니다. 이 연구의 목적은 미공개 및 진행 중인 시험(Open Science Framework)을 포함하여 이용 가능한 모든 무작위 임상 시험의 데이터를 사용하여 COVID-19 환자에서 위약 또는 무치료와 비교한 회복기 혈장 치료의 이점 및 모든 원인 사망률을 평가하는 것이었습니다. , https://doi.org/10.17605/OSF.IO/GEHFX ). 방법 이 공동의 체계적인 검토 및 메타 분석에서는 2021년 4월 8일까지 임상 시험 레지스트리(ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), Cochrane COVID-19 레지스터, LOVE 데이터베이스 및 PubMed를 검색했습니다. 게시된 결과가 없는 2021년 3월 1일까지 등록된 시험은 이메일을 통해 연락했습니다. 설정이나 치료 일정에 관계없이 COVID-19 환자에서 회복기 혈장을 위약 또는 무치료와 비교한 진행 중, 중단 및 완료된 무작위 임상 시험이 적격이었습니다. 집계된 사망률 데이터는 출판물에서 추출하거나 미공개 시험의 조사관이 제공했으며 Hartung-Knapp-Sidik-Jonkman 무작위 효과 모델을 사용하여 결합되었습니다. 우리는 전체 증거에 대한 미공개 시험의 기여도를 조사했습니다. 결과 총 16,477명의 환자가 33건의 시험에 포함되었습니다(20건의 미발표된 3,190명의 환자, 13건의 공개된 13,287명의 환자). 32건의 시험은 입원 환자만 등록했습니다(중환자실 환자만 있는 3건 포함). 비뚤림 위험은 29/33 시험에서 낮았습니다. 회복기 혈장을 투여받은 8495명의 환자 중 1997명이 사망했고(23%), 7982명의 대조군 환자 중 1952명이 사망했다(24%). 모든 원인으로 인한 사망률에 대한 결합된 위험 비율은 0.97(95% 신뢰 구간: 0.92; 1.02)이었고 연구 간 이질성은 우연을 넘어서지 않았습니다(I 2 = 0%). RECOVERY 시험은 메타분석에서 비중이 69.8%, 미공개 근거가 25.3%였다. 결론 COVID-19 환자의 회복기 혈장 치료는 모든 원인으로 인한 사망률을 줄이지 못했습니다. 이러한 결과는 COVID-19 환자에 대한 회복기 혈장 치료가 무작위 시험 외에 사용되어서는 안 된다는 강력한 증거를 제공합니다. 시험 조사관 간의 협력을 통한 증거 합성은 증거 생성과 환자 치료에 대한 증거 적용 모두에 정보를 제공할 수 있습니다. 보충 정보 온라인 버전에는 10.1186/s12879-021-06829-7에서 사용할 수 있는 보충 자료가 포함되어 있습니다.