tetano
Editor, Senior Moderator
J R Soc Med
. 2023 Nov 16:1410768231202657.
doi: 10.1177/01410768231202657. Online ahead of print. 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
Ping-Tao Tseng[SUP] 1 2 3 4 [/SUP], Bing-Syuan Zeng[SUP] 1 5 [/SUP], Chih-Wei Hsu[SUP] 6 [/SUP], Trevor Thompson[SUP] 7 [/SUP], Brendon Stubbs[SUP] 8 9 10 [/SUP], Po-Ren Hsueh[SUP] 11 12 [/SUP], Kuan-Pin Su[SUP] 13 14 15 [/SUP], Yen-Wen Chen[SUP] 3 [/SUP], Tien-Yu Chen[SUP] 16 17 [/SUP], Yi-Cheng Wu[SUP] 18 [/SUP], Pao-Yen Lin[SUP] 6 19 [/SUP], Andre F Carvalho[SUP] 20 [/SUP], Dian-Jeng Li[SUP] 21 [/SUP], Ta-Chuan Yeh[SUP] 16 [/SUP], Cheuk-Kwan Sun[SUP] 22 23 [/SUP], Yu-Shian Cheng[SUP] 2 24 [/SUP], Yow-Ling Shiue[SUP] 1 4 [/SUP], Chih-Sung Liang[SUP] 25 [/SUP], Yu-Kang Tu[SUP] 26 27 [/SUP]
Affiliations
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).
Keywords: COVID-19; Network meta-analysis; immunomodulatory kinase inhibitor; mortality; placebo.
. 2023 Nov 16:1410768231202657.
doi: 10.1177/01410768231202657. Online ahead of print. 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
Ping-Tao Tseng[SUP] 1 2 3 4 [/SUP], Bing-Syuan Zeng[SUP] 1 5 [/SUP], Chih-Wei Hsu[SUP] 6 [/SUP], Trevor Thompson[SUP] 7 [/SUP], Brendon Stubbs[SUP] 8 9 10 [/SUP], Po-Ren Hsueh[SUP] 11 12 [/SUP], Kuan-Pin Su[SUP] 13 14 15 [/SUP], Yen-Wen Chen[SUP] 3 [/SUP], Tien-Yu Chen[SUP] 16 17 [/SUP], Yi-Cheng Wu[SUP] 18 [/SUP], Pao-Yen Lin[SUP] 6 19 [/SUP], Andre F Carvalho[SUP] 20 [/SUP], Dian-Jeng Li[SUP] 21 [/SUP], Ta-Chuan Yeh[SUP] 16 [/SUP], Cheuk-Kwan Sun[SUP] 22 23 [/SUP], Yu-Shian Cheng[SUP] 2 24 [/SUP], Yow-Ling Shiue[SUP] 1 4 [/SUP], Chih-Sung Liang[SUP] 25 [/SUP], Yu-Kang Tu[SUP] 26 27 [/SUP]
Affiliations
- PMID: 37971412
- DOI: 10.1177/01410768231202657
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).
Keywords: COVID-19; Network meta-analysis; immunomodulatory kinase inhibitor; mortality; placebo.