Insights Into a "Negative" ICU Trial Derived From Gene Expression Profiling

Critical Care Medicine
Mary HoekstraJohn Muscedere

Abstract

Randomized controlled trials in the ICU often fail to show differences in endpoints between groups. We sought to explore reasons for this at a molecular level by analyzing transcriptomic data from a recent negative trial. Our objectives were to determine if randomization successfully balanced transcriptomic features between groups, to assess transcriptomic heterogeneity among the study subjects included, and to determine if the study drug had any effect at the gene expression level. Bioinformatics analysis of transcriptomic and clinical data collected in the course of a randomized controlled trial. Tertiary academic mixed medical-surgical ICU. Adult, critically ill patients expected to require invasive mechanical ventilation more than 48 hours. Lactoferrin or placebo delivered enterally and via an oral swab for up to 28 days. We found no major imbalances in transcriptomic features between groups. Unsupervised analysis did not reveal distinct clusters among patients at the time of enrollment. There were marked differences in gene expression between early and later time points. Patients in the lactoferrin group showed changes in the expression of genes associated with immune pathways known to be associated with lactoferrin. In th...Continue Reading

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Citations

Sep 27, 2020·Critical Care : the Official Journal of the Critical Care Forum·Zudin A PuthuchearyKonrad F R Schmidt

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