A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial
Abstract
Background Small observational studies suggest the effect of corticosteroids in patients with vasodilatory shock vary depending on endotypes determined by gene expression. We sought to replicate these findings in a larger cohort from a randomised clinical trial. Methods In a cross-sectional substudy of the Adjunctive Glucocorticoid Therapy In Septic Shock (ADRENAL) trial, patients were classified as one of two immune endotypes using predefined gene expression signatures: immune adaptive-prevalent (IA-P) or immune innate-prevalent (IN-P). We compared the outcomes of the two endotypes using a Bayesian analysis. The primary outcome was Day-28 mortality. Findings Of 540 patients, 267 (49.4%) were classified as IA-P and 273 (50.6%) as IN-P. In a Bayesian analysis using noninformative priors, there was no difference in the effect of hydrocortisone on 28-day mortality (odds ratio [OR] 1.43, 95% credible intervals [CrI] 0.72–2.87) and OR 1.39, 95% CrI 0.74–2.61, between the IA-P and IN-P groups, respectively. In the subgroup of patients with more severe shock (n = 215/540, 40%), the corresponding figures for IA-P and IN-P were 1.21, 95% CrI (0.31–4.74) and OR 0.72 (95% CrI 0.30–1.67), respectively. In the subgroup of patients with pulmonary sepsis (232/540, 43%), IA-P patients treated with hydrocortisone had increased mortality (OR 5.55, 95% CrI 1.81–21.2). Interpretation Gene expression data from patients with septic shock reveal distinct immune endotypes. There was no evidence of…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 540 participants or records.
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