Tseng, Ping-Tao ORCID: 0000-0001-5761-7800 , Zeng, Bing-Syuan, Hsu, Chih-Wei ORCID: 0000-0002-8650-4060 , Thompson, Trevor ORCID: 0000-0001-9880-782X , Stubbs, Brendon, Hsueh, Po-Ren, Su, Kuan-Pin, Chen, Yen-Wen, Chen, Tien-Yu, Wu, Yi-Cheng, Lin, Pao-Yen, Carvalho, Andre F, Li, Dian-Jeng, Yeh, Ta-Chuan, Sun, Cheuk-Kwan, Cheng, Yu-Shian, Shiue, Yow-Ling, Liang, Chih-Sung ORCID: 0000-0003-1138-5586 and Tu, Yu-Kang (2023) The difference in all-cause mortality between COVID-19 patients treated with standard of care plus placebo and those treated with standard of care alone: a network meta-analysis of randomised controlled trials of immunomodulatory kinase inhibitors. Journal of the Royal Society of Medicine. pp. 1-12. ISSN 0141-0768 (Print), 1758-1095 (Online) (doi:https://doi.org/10.1177/01410768231202657)

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Abstract

Objectives: The aim of this network meta-analysis (NMA) was to assess whether participants assigned to a placebo and standard of care (SoC) group had different major coronavirus disease 2019 (COVID-19)-related outcomes than those assigned to SoC alone.
Design: Frequentist model-based NMA.
Setting: We searched for randomised controlled trials (RCTs) of Janus kinase/Bruton tyrosine kinase inhibitors for the management of COVID-19.
Participants: Patients with COVID-19 infection.
Main outcome measures: The primary outcome was the 28-day all-cause mortality, and secondary outcomes were: (1) use of mechanical ventilation; (2) secondary bacterial infection; (3) acceptability (i.e. drop-out rate); and (4) safety (i.e. serious adverse events). We conducted an NMA using the frequentist model. Effect sizes were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs).
Results: We identified 14 eligible RCTs enrolling a total of 13,568 participants with COVID-19. Participants assigned to placebo plus SoC had a significantly higher risk of 28-day all-cause mortality than those receiving SoC alone (OR = 1.39, 95% CI = 1.07-1.79). This finding did not change substantially by subgroup analysis stratified by epidemiology factor, pandemic history progression and statistical methodologic consideration. In addition, none of the treatments investigated were associated with a significantly different risk of secondary bacterial infection, acceptability or safety compared with the SoC group.
Conclusions: This NMA suggested a higher all-cause mortality in patients treated with placebo plus SoC compared with those treated with SoC alone. However, caution is advised in interpreting these results due to the absence of a direct head-to-head comparison. Future research should critically evaluate the necessity of placebo administration in COVID-19 RCTs and consider alternative study designs to minimise potential biases. Trial registration: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022376217).

Item Type:	Article
Uncontrolled Keywords:	COVID-19; Network meta-analysis; immunomodulatory kinase inhibitor; mortality; placebo
Subjects:	B Philosophy. Psychology. Religion > BF Psychology Q Science > QR Microbiology > QR180 Immunology
Faculty / School / Research Centre / Research Group:	Faculty of Education, Health & Human Sciences Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development > Centre for Chronic Illness and Ageing Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	06 Dec 2023 16:27
URI:	http://gala.gre.ac.uk/id/eprint/45061

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