TY - JOUR

T1 - Lower or higher oxygenation targets for acute Hypoxaemic respiratory failure

T2 - Protocol for an individual patient data meta-analysis

AU - Nielsen, Frederik Mølgaard

AU - Klitgaard, Thomas Lass

AU - Bruun, Niels Henrik

AU - Møller, Morten Hylander

AU - Schjørring, Olav Lilleholt

AU - Rasmussen, Bodil Steen

N1 - Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

PY - 2023

Y1 - 2023

N2 - Background: Supplemental oxygen therapy is central to the treatment of acute hypoxaemic respiratory failure, a condition which remains a major driver for morbidity and mortality in intensive care. Despite several large randomised clinical trials comparing a higher versus a lower oxygenation target for these patients, significant differences in study design impede analysis of aggregate data and final clinical recommendations. Methods: This paper presents the protocol for conducting an individual patient data meta-analysis where full individual patient data according to the intention-to-treat principle will be pooled from the HOT-ICU and HOT-COVID trials in a one-step procedure. The two trials are near-identical in design. We plan to use a hierarchical general linear mixed model that accounts for data clustering at a trial and site level. The primary outcome will be 90-day all-cause mortality while the secondary outcome will be days alive without life-support at 90 days. Further, we outline 14 clinically relevant predefined subgroups which we will analyse for heterogeneity in the intervention effects and interactions, and we present a plan for assessing the credibility of the subgroup analyses. Conclusion: The presented individual patient data meta-analysis will synthesise individual level patient data from two of the largest randomised clinical trials on targeted oxygen therapy in intensive care. The results will provide a re-analysis of the intervention effects on the pooled intention-to-treat populations and facilitate subgroup analyses with an increased power to detect clinically important effect modifications.

AB - Background: Supplemental oxygen therapy is central to the treatment of acute hypoxaemic respiratory failure, a condition which remains a major driver for morbidity and mortality in intensive care. Despite several large randomised clinical trials comparing a higher versus a lower oxygenation target for these patients, significant differences in study design impede analysis of aggregate data and final clinical recommendations. Methods: This paper presents the protocol for conducting an individual patient data meta-analysis where full individual patient data according to the intention-to-treat principle will be pooled from the HOT-ICU and HOT-COVID trials in a one-step procedure. The two trials are near-identical in design. We plan to use a hierarchical general linear mixed model that accounts for data clustering at a trial and site level. The primary outcome will be 90-day all-cause mortality while the secondary outcome will be days alive without life-support at 90 days. Further, we outline 14 clinically relevant predefined subgroups which we will analyse for heterogeneity in the intervention effects and interactions, and we present a plan for assessing the credibility of the subgroup analyses. Conclusion: The presented individual patient data meta-analysis will synthesise individual level patient data from two of the largest randomised clinical trials on targeted oxygen therapy in intensive care. The results will provide a re-analysis of the intervention effects on the pooled intention-to-treat populations and facilitate subgroup analyses with an increased power to detect clinically important effect modifications.

KW - individual patient data meta-analysis

KW - intensive care

KW - supplemental oxygen therapy

U2 - 10.1111/aas.14220

DO - 10.1111/aas.14220

M3 - Journal article

C2 - 36807011

AN - SCOPUS:85150458533

VL - 67

SP - 811

EP - 819

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 6

ER -