A living WHO guideline on drugs for covid-19

Bram Rochwerg; Reed AC Siemieniuk; Thomas Agoritsas; François Lamontagne; Lisa Askie; Lyubov Lytvyn; Arnav Agarwal; Yee-Sin Leo; Helen Macdonald; Linan Zeng; Wagdy Amin; Erlina Burhan; Frederique 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; Natalia Pshenichnaya; Nida Qadir; Saniya Sabzwari; Rohit Sarin; Manu Shankar-Hari; Michael Sharland; Yinzhong Shen; Shalini Sri Ranganathan; Joao P Souza; Miriam Stegemann; An De Sutter; Sebastian Ugarte; Sridhar Venkatapuram; Vu Quoc Dat; Dubula Vuyiseka; Ananda Wijewickrama; Brittany Maguire; Dena Zeraatkar; Jessica J Bartoszko; Long Ge; Romina Brignardello-Petersen; Andrew Owen; Gordon Guyatt; Janet Diaz; Michael Jacobs; Per Olav Vandvik

doi:10.1136/bmj.m3379

A living WHO guideline on drugs for covid-19

Bram Rochwerg, Reed AC Siemieniuk, Thomas Agoritsas, François Lamontagne, Lisa Askie, Lyubov Lytvyn, Arnav Agarwal, Yee-Sin Leo, Helen Macdonald, Linan Zeng, Wagdy Amin, Erlina Burhan, Frederique Jacquerioz Bausch, Carolyn S Calfee, Maurizio Cecconi, Duncan Chanda, Bin Du, Heike Geduld, Patrick Gee, Nerina HarleyMadiha 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, Natalia Pshenichnaya, Nida Qadir, Saniya Sabzwari, Rohit Sarin, Manu Shankar-Hari, Michael Sharland, Yinzhong Shen, Shalini Sri Ranganathan, Joao P Souza, Miriam Stegemann, An De Sutter, Sebastian Ugarte, Sridhar Venkatapuram, Vu Quoc Dat, Dubula Vuyiseka, Ananda Wijewickrama, Brittany Maguire, Dena Zeraatkar, Jessica J Bartoszko, Long Ge, Romina Brignardello-Petersen, Andrew Owen, Gordon Guyatt, Janet Diaz, Michael Jacobs, Per Olav Vandvik

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Abstract

Clinical question What is the role of drug interventions in the treatment of patients with covid-19?New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial.Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects.Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers note This is the fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

Original language	English
Pages (from-to)	m3379
Journal	BMJ
Volume	370
DOIs	https://doi.org/10.1136/bmj.m3379
Publication status	Published - 4 Sept 2020

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10.1136/bmj.m3379

http://www.bmj.com/content/370/bmj.m3379.abstract

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@article{287294a12f7d40779f926a49e727a416,

title = "A living WHO guideline on drugs for covid-19",

abstract = "Clinical question What is the role of drug interventions in the treatment of patients with covid-19?New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial.Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects.Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers note This is the fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.",

author = "Bram Rochwerg and Siemieniuk, {Reed AC} and Thomas Agoritsas and Fran{\c c}ois Lamontagne and Lisa Askie and Lyubov Lytvyn and Arnav Agarwal and Yee-Sin Leo and Helen Macdonald and Linan Zeng and Wagdy Amin and Erlina Burhan and Bausch, {Frederique Jacquerioz} and Calfee, {Carolyn S} and Maurizio Cecconi and Duncan Chanda and Bin Du and Heike Geduld and Patrick Gee and Nerina Harley and Madiha Hashimi and Beverly Hunt and Kabra, {Sushil K} and Seema Kanda and Leticia Kawano-Dourado and Yae-Jean Kim and Niranjan Kissoon and Arthur Kwizera and Imelda Mahaka and Hela Manai and Greta Mino and Emmanuel Nsutebu and Natalia Pshenichnaya and Nida Qadir and Saniya Sabzwari and Rohit Sarin and Manu Shankar-Hari and Michael Sharland and Yinzhong Shen and Ranganathan, {Shalini Sri} and Souza, {Joao P} and Miriam Stegemann and {De Sutter}, An and Sebastian Ugarte and Sridhar Venkatapuram and Dat, {Vu Quoc} and Dubula Vuyiseka and Ananda Wijewickrama and Brittany Maguire and Dena Zeraatkar and Bartoszko, {Jessica J} and Long Ge and Romina Brignardello-Petersen and Andrew Owen and Gordon Guyatt and Janet Diaz and Michael Jacobs and Vandvik, {Per Olav}",

year = "2020",

month = sep,

day = "4",

doi = "10.1136/bmj.m3379",

language = "English",

volume = "370",

pages = "m3379",

journal = "BMJ",

issn = "0959-8138",

publisher = "BMJ Publishing Group Ltd",

}

Rochwerg, B, Siemieniuk, RAC, Agoritsas, T, Lamontagne, F, Askie, L, Lytvyn, L, Agarwal, A, Leo, Y-S, Macdonald, H, Zeng, L, Amin, W, Burhan, E, Bausch, FJ, Calfee, CS, Cecconi, M, Chanda, D, Du, B, Geduld, H, Gee, P, Harley, N, Hashimi, M, Hunt, B, Kabra, SK, Kanda, S, Kawano-Dourado, L, Kim, Y-J, Kissoon, N, Kwizera, A, Mahaka, I, Manai, H, Mino, G, Nsutebu, E, Pshenichnaya, N, Qadir, N, Sabzwari, S, Sarin, R, Shankar-Hari, M, Sharland, M, Shen, Y, Ranganathan, SS, Souza, JP, Stegemann, M, De Sutter, A, Ugarte, S, Venkatapuram, S, Dat, VQ, Vuyiseka, D, Wijewickrama, A, Maguire, B, Zeraatkar, D, Bartoszko, JJ, Ge, L, Brignardello-Petersen, R, Owen, A, Guyatt, G, Diaz, J, Jacobs, M & Vandvik, PO 2020, 'A living WHO guideline on drugs for covid-19', BMJ, vol. 370, pp. m3379. https://doi.org/10.1136/bmj.m3379

TY - JOUR

T1 - A living WHO guideline on drugs for covid-19

AU - Rochwerg, Bram

AU - Siemieniuk, Reed AC

AU - Agoritsas, Thomas

AU - Lamontagne, François

AU - Askie, Lisa

AU - Lytvyn, Lyubov

AU - Agarwal, Arnav

AU - Leo, Yee-Sin

AU - Macdonald, Helen

AU - Zeng, Linan

AU - Amin, Wagdy

AU - Burhan, Erlina

AU - Bausch, Frederique Jacquerioz

AU - Calfee, Carolyn S

AU - Cecconi, Maurizio

AU - Chanda, Duncan

AU - Du, Bin

AU - Geduld, Heike

AU - Gee, Patrick

AU - Harley, Nerina

AU - Hashimi, Madiha

AU - Hunt, Beverly

AU - Kabra, Sushil K

AU - Kanda, Seema

AU - Kawano-Dourado, Leticia

AU - Kim, Yae-Jean

AU - Kissoon, Niranjan

AU - Kwizera, Arthur

AU - Mahaka, Imelda

AU - Manai, Hela

AU - Mino, Greta

AU - Nsutebu, Emmanuel

AU - Pshenichnaya, Natalia

AU - Qadir, Nida

AU - Sabzwari, Saniya

AU - Sarin, Rohit

AU - Shankar-Hari, Manu

AU - Sharland, Michael

AU - Shen, Yinzhong

AU - Ranganathan, Shalini Sri

AU - Souza, Joao P

AU - Stegemann, Miriam

AU - De Sutter, An

AU - Ugarte, Sebastian

AU - Venkatapuram, Sridhar

AU - Dat, Vu Quoc

AU - Vuyiseka, Dubula

AU - Wijewickrama, Ananda

AU - Maguire, Brittany

AU - Zeraatkar, Dena

AU - Bartoszko, Jessica J

AU - Ge, Long

AU - Brignardello-Petersen, Romina

AU - Owen, Andrew

AU - Guyatt, Gordon

AU - Diaz, Janet

AU - Jacobs, Michael

AU - Vandvik, Per Olav

PY - 2020/9/4

Y1 - 2020/9/4

N2 - Clinical question What is the role of drug interventions in the treatment of patients with covid-19?New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial.Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects.Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers note This is the fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

AB - Clinical question What is the role of drug interventions in the treatment of patients with covid-19?New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial.Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects.Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers note This is the fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

U2 - 10.1136/bmj.m3379

DO - 10.1136/bmj.m3379

M3 - Article

SN - 0959-8138

VL - 370

SP - m3379

JO - BMJ

JF - BMJ

ER -

A living WHO guideline on drugs for covid-19

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