Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)


Autoři: Sophie Juul aff001;  Emil Eik Nielsen aff001;  Joshua Feinberg aff001;  Faiza Siddiqui aff001;  Caroline Kamp Jørgensen aff001;  Emily Barot aff001;  Niklas Nielsen aff003;  Peter Bentzer aff003;  Areti Angeliki Veroniki aff004;  Lehana Thabane aff006;  Fanlong Bu aff007;  Sarah Klingenberg aff001;  Christian Gluud aff001;  Janus Christian Jakobsen aff001
Působiště autorů: Copenhagen Trial Unit–Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark aff001;  Department of Internal Medicine–Cardiology Section, Holbæk Hospital, Holbæk, Denmark aff002;  Lund University, Helsingborg Hospital, Department of Clinical Sciences Lund, Anesthesia & Intensive Care, Lund, Sweden aff003;  Department of Primary Education, School of Education, University of Ioannina, Ioannina, Greece aff004;  Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada aff005;  Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada aff006;  Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China aff007;  Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark aff008
Vyšlo v časopise: Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project). PLoS Med 17(9): e1003293. doi:10.1371/journal.pmed.1003293
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003293

Souhrn

Background

Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed.

Methods and findings

This is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology.

We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62–0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40–1.37; p = 0.34, I2 = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80–1.11; p = 0.48, I2 = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63–0.94; p = 0.009, I2 = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial.

Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I2 = 0%; 7 trials; low certainty) and serious adverse events (RR 1.07; 95% CI 0.96–1.18; p = 0.21; I2 = 0%; 7 trials; low certainty) by 20% or more, and meta-analysis showed evidence of a harmful effect on nonserious adverse events (RR 2.40; 95% CI 2.01–2.87; p < 0.00001; I2 = 90%; 6 trials; very low certainty). Meta-analysis showed no evidence of a difference between lopinavir–ritonavir versus standard care on serious adverse events (RR 0.64; 95% CI 0.39–1.04; p = 0.07, I2 = 0%; 2 trials; very low certainty) or nonserious adverse events (RR 1.14; 95% CI 0.85–1.53; p = 0.38, I2 = 75%; 2 trials; very low certainty). Meta-analysis showed no evidence of a difference between convalescent plasma versus standard care on all-cause mortality (RR 0.60; 95% CI 0.33–1.10; p = 0.10, I2 = 0%; 2 trials; very low certainty). Five single trials showed statistically significant results but were underpowered to confirm or reject realistic intervention effects.

None of the remaining trials showed evidence of a difference on our predefined outcomes. Because of the lack of relevant data, it was not possible to perform other meta-analyses, network meta-analysis, or individual patient data meta-analyses. The main limitation of this living review is the paucity of data currently available. Furthermore, the included trials were all at risks of systematic errors and random errors.

Conclusions

Our results show that dexamethasone and remdesivir might be beneficial for COVID-19 patients, but the certainty of the evidence was low to very low, so more trials are needed. We can exclude the possibility of hydroxychloroquine versus standard care reducing the risk of death and serious adverse events by 20% or more. Otherwise, no evidence-based treatment for COVID-19 currently exists. This review will continuously inform best practice in treatment and clinical research of COVID-19.

Klíčová slova:

Adverse events – COVID 19 – Database searching – Chloroquine – Interferons – Medical risk factors – Metaanalysis – Research errors


Zdroje

1. Guan W, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032 32109013

2. World Health Organization. Novel Coronavirus (2019-nCOV). Situation Report 51. 2020. [cited 2020 Aug 7]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10

3. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382:1787–1799. doi: 10.1056/NEJMoa2001282 32187464

4. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5 31986264

5. Chan JF, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–23. doi: 10.1016/S0140-6736(20)30154-9 31986261

6. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2. doi: 10.1016/S2213-2600(20)30076-X 32085846

7. Baden LR, Rubin EJ. Covid-19—The search for effective therapy. New England Journal of Medicine. 2020. doi: 10.1056/NEJMe2005477 [Epub ahead of print] 32187463

8. Fauci AS, Lane HC, Redfield RR. Covid-19—Navigating the uncharted. N Engl J Med. 2020;382:1268–1269. doi: 10.1056/NEJMe2002387 32109011

9. Juul S, Nielsen N, Bentzer P, Veroniki AA, Thabane L, Linder A, et al. Interventions for treatment of COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING Project). Syst Rev. 2020;9(1):108. doi: 10.1186/s13643-020-01371-0 32386514

10. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7). doi: 10.1371/journal.pmed.1000097 19621072

11. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. BMJ. 2009;339(b2700).

12. Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. [cited 2020 Aug 7]. Available from: www.training.cochrane.org/handbook

13. The Cochrane Collaboration. Cochrane COVID-19 Study Register [Internet]. [cited 2020 Aug 7]. Available from: https://covid-19.cochrane.org/

14. Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ. A real-time dashboard of clinical trials for COVID-19. Lancet Dig Health. 2020;2(6):E286–E287. doi: 10.1016/S2589-7500(20)30086-8 32363333

15. Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366. doi: 10.1136/bmj.l4898 31462531

16. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice (ICH-GCP). 2015. [cited 2020 Jul 4]. Available from: https://ichgcp.net/.

17. Keus F, Wetterslev J, Gluud C, van Laarhoven CJ. Evidence at a glance: error matrix approach for overviewing available evidence. BMC Med Res Methodol. 2010;10(1):90.

18. Jakobsen JC, Wetterslev J, Winkel P, Lange T, Gluud C. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods. BMC Med Res Methodol. 2014;14(1):120.

19. Review Manager (RevMan). Version 5.4. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2020.

20. StataCorp. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC.2019.

21. Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011. [cited 2020 Aug 7] Available from: https://handbook-5-1.cochrane.org/.

22. Higgins JP, Spiegelhalter DJ. Being sceptical about meta-analyses: a Bayesian perspective on magnesium trials in myocardial infarction. Int J Epidemiol. 2002;31(1):96–104. doi: 10.1093/ije/31.1.96 11914302

23. Copenhagen Trial Unit. TSA—Trial Sequential Analysis. [cited 2020 Jul 6]. Available from: http://www.ctu.dk/tsa/.

24. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2008;61(1):64–75. doi: 10.1016/j.jclinepi.2007.03.013 18083463

25. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61(8):763–9. doi: 10.1016/j.jclinepi.2007.10.007 18411040

26. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta-analyses may be inconclusive—trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol. 2008;38(1):287–98. doi: 10.1093/ije/dyn188 18824466

27. Thorlund K, Devereaux P, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses? Int J Epidemiol. 2008;38(1):276–86 doi: 10.1093/ije/dyn179 18824467

28. Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol. 2009;9(1):86.

29. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud, C. User manual for trial sequential analysis (TSA). 2011. [cited 2020 Jul 4]. Available from: http://wwwctudk/tsa/files/tsa_manualpdf

30. Thorlund K, Anema A, Mills E. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals. Clin Epidemiol. 2010;2:57. doi: 10.2147/clep.s9242 20865104

31. Imberger G, Thorlund K, Gluud C, Wetterslev J. False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review. BMJ Open. 2016;6(8):e011890. doi: 10.1136/bmjopen-2016-011890 27519923

32. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19—Preliminary report. N Engl J Med. 2020. doi: 10.1056/NEJMoa2007764 32445440

33. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. Epub 2020. doi: 10.1056/NEJMoa200128

34. Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, et al. Favipiravir versus arbidol for COVID-19: A randomized clinical trial. medRxiv. 2020:2020.03.17.20037432. [preprint]

35. Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci). 2020;49(1).

36. Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. 2020:2020.03.22.20040758. [preprint]

37. Davoudi-Monfared E, Rahmani H, Khalili H, Hajiabdolbaghi M, Salehi M, Abbasian L, et al. Efficacy and safety of interferon beta-1a in treatment of severe COVID-19: A randomized clinical trial. medRxiv. 2020. doi: 10.1101/2020.05.28.20116467 [Preprint]

38. Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med. Epub 2020. doi: 10.1056/NEJMoa2015301 32459919

39. Hung IF-N, Lung K-C, Tso EY-K, Liu R, Chung TW-H, Chu M-Y, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;395: 1695–704 doi: 10.1016/S0140-6736(20)31042-4 32401715

40. Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: A randomized clinical trial. JAMA. 2020;324(5):460–470. doi: 10.1001/jama.2020.10044 32492084

41. Li Y, Xie Z, Lin W, et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Cell Press. 2020 [Pre-proof]

42. Lou Y, Liu L, Yao H, Hu X, Su J, Xu K, et al. Clinical outcomes and plasma concentrations of baloxavir marboxil and favipiravir in COVID-19 patients: An exploratory randomized, controlled trial. medRxiv. 2020. https://doi.org/10.1101/2020.04.29.20085761 [preprint]

43. Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:1849.

44. Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):P1569–1578. doi: 10.1016/S0140-6736(20)31022-9 32423584

45. Wu CN, Xia LZ, Li KH, Ma WH, Yu DN, Qu B, et al. High-flow nasal-oxygenation-assisted fibreoptic tracheal intubation in critically ill patients with COVID-19 pneumonia: a prospective randomised controlled trial. Br J Anaesth. 2020;125(1):E166–E168. doi: 10.1016/j.bja.2020.02.020 32200994

46. Zheng F, Zhou Y, Zhou Z, Ye F, Huang B, Huang Y, et al. A novel protein drug, novaferon, as the potential antiviral drug for COVID-19. medRxiv. 2020. https://doi.org/10.1101/2020.04.24.20077735 [preprint]

47. Zhong M, Sun A, Xiao T, Yao G, Sang L, Zheng X, et al. A randomized, single-blind, group sequential, active-controlled study to evaluate the clinical efficacy and safety of α-lipotic acid for critically ill patients with coronavirus disease 2019 (COVID-19). medRxiv. 2020. 2020.04.15.20066266. [preprint]

48. Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19 –Preliminary report. medRxiv. 2020. https://doi.org/10.1101/2020.06.22.20137273 [preprint]

49. Chen L, Zhang Z-Y, Fu J-G, et al. Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study. medRxiv. 2020. https://doi.org/10.1101/2020.06.19.20136093 [preprint]

50. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: The GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136 32579195

51. Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. JAMA Netw Open. 2020;3(4).

52. Gharbharan A, Jordans CCE, Geurtsvankessel C, et al. Convalescent plasma for COVID-19. A randomized clinical trial. medrRxiv. 2020: https://doi.org/10.1101/2020.07.01.20139857 [Preprint]

53. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19—Preliminary report. N Engl J Med. Epub 2020. doi: 10.1056/NEJMoa2021436 32678530

54. Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann Intern Med. 2020. https://doi.org/10.7326/M20-4207. [Epub ahead of print]

55. Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. Epub 2020. doi: 10.1056/NEJMoa2019014 32706953

56. Mitjà O, Corbacho-Monné M, Ubals M, et al. Hydroxychloroquine for early treatment of adults with mild covid-19: a randomized-controlled trial. Clin Infect Dis. Epub 2020. https://doi.org/10.1093/cid/ciaa1009

57. Corral-Gudino L, Bahamonde A, Arnaiz delas Revillas F, et al. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. 2020. doi: 10.1101/2020.06.17.20133579 [Preprint]

58. Sakoulas G, Geriak M, Kullar R, et al. Intravenous Immunoglobulin (IVIG) significantly reduces respiratory morbidity in COVID-19 pneumonia: a prospective randomized trial. medRxiv. 2020. https://doi.org/10.1101/2020.07.20.20157891. [Preprint]

59. Horby P, Mafham M, Linsell L, et al. Effect of hydroxychloroquine in hospitalized patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. medRxiv. 2020. https://doi.org/10.1101/2020.07.15.20151852. [Preprint]

60. Chen C-P, Lin Y-C, Chen T-C, et al. A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19). medRxiv. 2020. doi: 10.1101/2020.07.08.20148841 [Preprint]

61. Chen J, Xia L, Liu L, et al. Antiviral activity and safety of darunavir/cobicistat for the treatment of COVID-19. Open Forum Infect Dis. 2020;7(7).

62. Chen Y-K, Huang Y-Q, Tang S-Q, et al. Comparative effectiveness and safety of ribavirin plus interferon-alpha, lopinavir/ritonavir plus interferon-alpha and ribavirin plus lopinavir/ritonavir plus interferon-alpha in patients with mild to moderate novel coronavirus pneumonia: results of a randomized, open-labeled prospective study. SSRN. 2020. http://dx.doi.org/10.2139/ssrn.3576905. [Preprint]

63. Guvenmez O, Keskin H, Ay B, et al. The comparison of the effectiveness of Lincocin® and Azitro® in the treatment of covid-19-associated pneumonia: A prospective study. J Popul Ther Clin Pharmacol. 2020;27(SP1):e5–e10.

64. Yuan X, Yi W, Liu B, et al. Pulmonary radiological change of COVID-19 patients with 99mTc-MDP treatment. medRxiv. 2020. https://doi.org/10.1101/2020.04.07.20054767. [Preprint]

65. Idelsis E-M, Jesus P-E, Yaquelin D-R, et al. Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. medRxiv. 2020. https://doi.org/10.1101/2020.07.29.20164251. [Preprint]

66. Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020. doi: 10.1016/j.jaci.2020.05.019 32470486

67. Davoodi L, Abedi SM, Salehifar E, et al. Febuxostat therapy in outpatients with suspected COVID-19: A clinical trial. Int J Clin Pract. 2020:e13600.

68. Lofgren SMM, Nicol MR, Bangdiwala AS, et al. Safety of hydroxychloroquine among outpatient clinical trial participants for COVID-19. medRxiv. 2020. https://doi.org/10.1101/2020.07.16.20155531 [Preprint]

69. Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on hydroxychloroquine 5 June 2020. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. [cited 2020 Jul 4]. Available from: https://www.recoverytrial.net/files/hcq-recovery-statement-050620-final-002.pdf

70. Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial on lopinavir-ritonavir 29 June 2020. No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY. [cited 2020 Jul 4]. Available from: https://www.recoverytrial.net/files/lopinavir-ritonavir-recovery-statement-29062020_final.pdf

71. Dimairo M, Pallmann P, Wason J, et al. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020;369:m115. https://doi.org/10.1136/bmj.m115 [Epub ahead of print] doi: 10.1136/bmj.m115 32554564

72. Morris T, Dahly D, Hood K, et al. Statistical review of effect of dexamethasone in hospitalized patients with COVID-19 –preliminary report. Zenodo. 2020. doi: 10.5281/zenodo.3928540

73. Savović J, Turner RM, Mawdsley D, et al. Association between risk-of-bias assessments and results of randomized trials in Cochrane reviews: the ROBES meta-epidemiologic study. Am J Epidemiol. 2018;187(5):1113–22. doi: 10.1093/aje/kwx344 29126260

74. Jakobsen JC, Gluud C, Winkel P, et al. The thresholds for statistical and clinical significance–a five-step procedure for evaluation of intervention effects in randomised clinical trials. BMC Med Res Methodol. 2014;14(1):1–12.

75. World Health Organization. Coronavirus disease (COVID-19) outbreak 2020. [cited 2020 Jul 5]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019

76. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020. https://doi.org/10.1016/S0140-6736(20)31180-6 [Epub ahead of print] [Retracted]

77. Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020;370:m2980. doi: 10.1136/bmj.m2980 32732190

78. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA. 2020;323(18):1824–1836. doi: 10.1001/jama.2020.6019 32282022

79. Boutron I, Ravaud P, Chaimani A, Tovey D, Devane D, Meerpohl J, et al. Living mapping and living systematic review of Covid-19 studies. 2020 [cited 2020 Aug 7]. Available from: www.covid-nma.com.

80. Rios P, Radhakrishnan A, Antony J, Thomas SM, Muller M, Straus SE, et al. Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review. medRxiv. 2020.03.19.20039008 [preprint]


Článek vyšel v časopise

PLOS Medicine


2020 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Imunitní trombocytopenie (ITP) u dospělých pacientů
nový kurz
Autoři: prof. MUDr. Tomáš Kozák, Ph.D., MBA

Pěnová skleroterapie
Autoři: MUDr. Marek Šlais

White paper - jak vidíme optimální péči o zubní náhrady
Autoři: MUDr. Jindřich Charvát, CSc.

Hemofilie - série kurzů

Faktory ovlivňující léčbu levotyroxinem
Autoři:

Všechny kurzy
Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×