Drug treatments for covid-19: living systematic review and network meta-analysis.
Reed A C Siemieniuk,Jessica J Bartoszko,Long Ge,Dena Zeraatkar,Ariel Izcovich,Elena Kum,Hector Pardo-Hernandez,Anila Qasim,Juan Pablo Diaz Martinez,Bram Rochwerg,Francois Lamontagne,Mi Ah Han,Qin Liu,Arnav Agarwal,Arnav Agarwal,Thomas Agoritsas,Derek K. Chu,Rachel Couban,Ellen Cusano,Andrea Darzi,Tahira Devji,Bo Fang,Carmen Fang,Signe Flottorp,Signe Flottorp,Farid Foroutan,Farid Foroutan,Maryam Ghadimi,Diane Heels-Ansdell,Kimia Honarmand,Liangying Hou,Xiaorong Hou,Quazi Ibrahim,Assem M. Khamis,Bonnie Lam,Mark Loeb,Maura Marcucci,Shelley McLeod,Sharhzad Motaghi,Srinivas Murthy,Reem A. Mustafa,Reem A. Mustafa,John Neary,Gabriel Rada,Irbaz Bin Riaz,Behnam Sadeghirad,Nigar Sekercioglu,Lulu Sheng,Ashwini Sreekanta,Charlotte Switzer,Britta Tendal,Lehana Thabane,George Tomlinson,Tari Turner,Per Olav Vandvik,Robin W.M. Vernooij,Andrés Viteri-García,Ying Wang,Liang Yao,Zhikang Ye,Gordon H Guyatt,Romina Brignardello-Petersen +61 more
Reads0
Chats0
TLDR
Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care and the effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.Abstract:
Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is publicly available in the supplementary material. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.read more
Citations
More filters
Journal ArticleDOI
A living WHO guideline on drugs for covid-19
Bram Rochwerg,Arnav Agarwal,Reed A C Siemieniuk,Thomas Agoritsas,Francois Lamontagne,Lisa Askie,Lyubov Lytvyn,Yee Sin Leo,Helen Macdonald,Linan Zeng,Wagdy Amin,Erlina Burhan,Frédérique Jacquerioz Bausch,Carolyn S. Calfee,Maurizio Cecconi,Duncan Chanda,Bin Du,Heike Geduld,Patrick Gee,Nerina Harley,Madiha Hashimi,Beverly Hunt,Sushil K. Kabra,Seema Kanda,Leticia Kawano-Dourado,Yae-Jean Kim,Niranjan Kissoon,Arthur Kwizera,Imelda Mahaka,Hela Manai,Greta Mino,Emmanuel Nsutebu,Jacobus Preller,Natalia Pshenichnaya,Nida Qadir,Saniya Sabzwari,Rohit Sarin,Manu Shankar-Hari,Mike Sharland,Yinzhong Shen,Shalini Sri Ranganathan,João Paulo Souza,Miriam Stegemann,An De Sutter,Sebastian Ugarte,Sridhar Venkatapuram,Vu Quoc Dat,Dubula Vuyiseka,Ananda Wijewickrama,Brittany J. Maguire,Dena Zeraatkar,Jessica J Bartoszko,Long Ge,Long Ge,Romina Brignardello-Petersen,Andrew Owen,Gordon H. Guyatt,Janet V. Diaz,Michael Jacobs,Per Olav Vandvik +59 more
TL;DR: A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice, containing a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic cortiosteroids for non-severe patients.
Journal ArticleDOI
Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Derek C. Angus,Lennie P. G. Derde,Farah Al-Beidh,Djillali Annane,Yaseen M. Arabi,Abi Beane,Wilma van Bentum-Puijk,Lindsay R. Berry,Zahra Bhimani,Marc J. M. Bonten,Charlotte Bradbury,Frank M. Brunkhorst,Meredith Buxton,Adrian Buzgau,Allen C. Cheng,Menno de Jong,Michelle A. Detry,Lise J Estcourt,Lise J Estcourt,Mark Fitzgerald,Herman Goossens,Cameron Green,Rashan Haniffa,Alisa Higgins,Christopher M. Horvat,Sebastiaan J. Hullegie,Peter Kruger,Francois Lamontagne,Patrick R. Lawler,Kelsey Linstrum,Edward Litton,Elizabeth Lorenzi,John E. A. Marshall,John E. A. Marshall,Daniel F. McAuley,Anna McGlothin,Shay McGuinness,Shay McGuinness,Shay McGuinness,Bryan J. McVerry,Stephanie K. Montgomery,Paul R Mouncey,Srinivas Murthy,Alistair Nichol,Rachael Parke,Rachael Parke,Rachael Parke,Jane Parker,Kathryn M Rowan,Ashish Sanil,Marlene Santos,Christina Saunders,Christopher W. Seymour,Anne Turner,Frank L. van de Veerdonk,Balasubramanian Venkatesh,Balasubramanian Venkatesh,Ryan Zarychanski,Scott M. Berry,Roger J. Lewis,Roger J. Lewis,Colin McArthur,Steven A R Webb,Steven A R Webb,Steven A R Webb,Anthony C. Gordon +65 more
TL;DR: To determine whether hydrocortisone improves outcome for patients with severe COVID-19, an ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin was conducted.
Journal ArticleDOI
COVID-19-neutralizing antibodies predict disease severity and survival.
Wilfredo F. Garcia-Beltran,Evan C. Lam,Michael G Astudillo,Diane Yang,Tyler E. Miller,Jared Feldman,Blake M. Hauser,Timothy M. Caradonna,Kiera L. Clayton,Adam Nitido,Mandakolathur R. Murali,Galit Alter,Richelle C. Charles,Anand S. Dighe,John A. Branda,Jochen K. Lennerz,Daniel Lingwood,Aaron G. Schmidt,A. John Iafrate,Alejandro B. Balazs +19 more
TL;DR: It is found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels, highlighting the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.
Journal ArticleDOI
Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial.
Gilmar Reis,M Helena Vasconcelos,Eduardo Augusto dos Santos Moreira-Silva,Daniela Carla Medeiros Silva,Lehana Thabane,Aline Cruz Milagres,Thiago Santiago Ferreira,Castilho Vitor Quirino dos Santos,Vitoria Helena de Souza Campos,Ana Maria Ribeiro Nogueira,Ana Paula Figueiredo Guimaraes de Almeida,Eduardo Diniz Callegari,Adhemar Dias de Figueiredo Neto,Leonardo Cançado Monteiro Savassi,Maria Izabel Campos Simplicio,Luciene Barra Ribeiro,Rosemary Oliveira,Ofir Harari,Jamie I Forrest,Hinda Ruton,Sheila Sprague,Paula McKay,Alla V. Glushchenko,Craig R. Rayner,Craig R. Rayner,Eric J. Lenze,Angela M. Reiersen,Gordon H. Guyatt,Edward J Mills +28 more
TL;DR: The TOGETHER trial as discussed by the authors evaluated the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to CoV-19.
Journal ArticleDOI
Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial
TL;DR: The TOGETHER trial as discussed by the authors evaluated the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID19.
References
More filters
Journal ArticleDOI
RoB 2: a revised tool for assessing risk of bias in randomised trials.
Jonathan A C Sterne,Jelena Savović,Jelena Savović,Matthew J. Page,Roy G Elbers,Natalie S Blencowe,Isabelle Boutron,Isabelle Boutron,Isabelle Boutron,Christopher J Cates,Hung-Yuan Cheng,Mark Corbett,Sandra Eldridge,Jonathan Emberson,Miguel A. Hernán,Sally Hopewell,Asbjørn Hróbjartsson,Asbjørn Hróbjartsson,Daniela R Junqueira,Peter Jüni,Jamie J Kirkham,Toby J Lasserson,Tianjing Li,Alexandra McAleenan,Barnaby C Reeves,Sasha Shepperd,Ian Shrier,Lesley A. Stewart,Kate Tilling,Ian R. White,Penny Whiting,Penny Whiting,Julian P T Higgins,Julian P T Higgins +33 more
TL;DR: The Cochrane risk-of-bias tool has been updated to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
Journal ArticleDOI
Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
Journal ArticleDOI
Dexamethasone in Hospitalized Patients with Covid-19
Peter Horby,Wei Shen Lim,Jonathan Emberson,M Mafham,Jennifer L Bell,Louise Linsell,Natalie Staplin,Christopher E. Brightling,Andrew Ustianowski,E Elmahi,B Prudon,Christopher A Green,Timothy Felton,David Chadwick,K Rege,C Fegan,Lucy C Chappell,Saul N. Faust,Thomas Jaki,Katie Jeffery,Alan A Montgomery,Kathryn M Rowan,Edmund Juszczak,J K Baillie,Richard Haynes,Martin J Landray +25 more
TL;DR: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
Journal ArticleDOI
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
Bin Cao,Yeming Wang,Danning Wen,Wen Liu,Jingli Wang,Guohui Fan,Lianguo Ruan,Bin Song,Yanping Cai,Ming Wei,Xingwang Li,Jia'an Xia,Nanshan Chen,Jie Xiang,Ting Yu,Tao Bai,Xuelei Xie,Li Zhang,Caihong Li,Ye Yuan,Hua Chen,Huadong Li,Hanping Huang,Shengjing Tu,Fengyun Gong,Ying Liu,Yuan Wei,Chongya Dong,Fei Zhou,Xiaoying Gu,Jiuyang Xu,Zhibo Liu,Yi Zhang,Li Hui,Lianhan Shang,Ke Wang,Kunxia Li,Xia Zhou,Xuan Dong,Zhaohui Qu,Sixia Lu,Xujuan Hu,Shunan Ruan,Shanshan Luo,Jing Wu,Lu Peng,Fang Cheng,Lihong Pan,Jun Zou,Chunmin Jia,Juan Wang,Xia Liu,Shuzhen Wang,Xudong Wu,Qin Ge,Jing He,Haiyan Zhan,Fang Qiu,Li Guo,Chaolin Huang,Thomas Jaki,Frederick G. Hayden,Peter Horby,Dingyu Zhang,Chen Wang +64 more
TL;DR: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care, and future trials in patients withsevere illness may help to confirm or exclude the possibility of a treatment benefit.
Journal ArticleDOI
The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations
Brian Hutton,Georgia Salanti,Deborah M Caldwell,Anna Chaimani,Christopher H. Schmid,Chris Cameron,John P. A. Ioannidis,Sharon E. Straus,Kristian Thorlund,Jeroen P. Jansen,Cynthia D. Mulrow,Ferrán Catalá-López,Peter C Gøtzsche,Kay Dickersin,Isabelle Boutron,Douglas G. Altman,David Moher +16 more
TL;DR: The process of developing specific advice for the reporting of systematic reviews that incorporate network meta-analyses is described, and the guidance generated from this process is presented.
Related Papers (5)
Dexamethasone in Hospitalized Patients with Covid-19
Peter Horby,Wei Shen Lim,Jonathan Emberson,M Mafham,Jennifer L Bell,Louise Linsell,Natalie Staplin,Christopher E. Brightling,Andrew Ustianowski,E Elmahi,B Prudon,Christopher A Green,Timothy Felton,David Chadwick,K Rege,C Fegan,Lucy C Chappell,Saul N. Faust,Thomas Jaki,Katie Jeffery,Alan A Montgomery,Kathryn M Rowan,Edmund Juszczak,J K Baillie,Richard Haynes,Martin J Landray +25 more
Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
Bin Cao,Yeming Wang,Danning Wen,Wen Liu,Jingli Wang,Guohui Fan,Lianguo Ruan,Bin Song,Yanping Cai,Ming Wei,Xingwang Li,Jia'an Xia,Nanshan Chen,Jie Xiang,Ting Yu,Tao Bai,Xuelei Xie,Li Zhang,Caihong Li,Ye Yuan,Hua Chen,Huadong Li,Hanping Huang,Shengjing Tu,Fengyun Gong,Ying Liu,Yuan Wei,Chongya Dong,Fei Zhou,Xiaoying Gu,Jiuyang Xu,Zhibo Liu,Yi Zhang,Li Hui,Lianhan Shang,Ke Wang,Kunxia Li,Xia Zhou,Xuan Dong,Zhaohui Qu,Sixia Lu,Xujuan Hu,Shunan Ruan,Shanshan Luo,Jing Wu,Lu Peng,Fang Cheng,Lihong Pan,Jun Zou,Chunmin Jia,Juan Wang,Xia Liu,Shuzhen Wang,Xudong Wu,Qin Ge,Jing He,Haiyan Zhan,Fang Qiu,Li Guo,Chaolin Huang,Thomas Jaki,Frederick G. Hayden,Peter Horby,Dingyu Zhang,Chen Wang +64 more