Steroid, thiamine, and ascorbic acid for comatose out-of-hospital cardiac arrest survivors (STAR): a randomised, placebo-controlled, phase 2 trial

초록

Background: Pharmacologic neuroprotection for out-of-hospital cardiac arrest (OHCA) remains elusive. We evaluated whether early hydrocortisone, ascorbic acid, and thiamine reduced neuronal injury in comatose OHCA survivors. Methods: In this multicentre, placebo-controlled trial across four South Korean hospitals, comatose adult OHCA survivors undergoing targeted temperature management were randomly assigned (1:1) to intravenous hydrocortisone (100 mg), ascorbic acid (50 mg/kg), and thiamine (200 mg) every 12 h for 3 days, or placebo. Randomisation was computer-generated. Bedside clinicians were aware of treatment allocation, whereas laboratory personnel and independent outcome assessors were masked. The primary outcome was peak neuron-specific enolase (NSE) concentration, defined as the highest available value measured at 48 h or 72 h after return of spontaneous circulation. Efficacy was analysed using a modified intention-to-treat (mITT) principle, with multiple imputation for the full intention-to-treat (ITT) population. The completed trial was registered with ClinicalTrials.gov on June 4, 2021 (NCT04921189). Findings: Between Dec 31, 2021, and Dec 7, 2024, 160 participants (123 male, 37 female) were assigned (80 per group); 147 were included in the mITT analysis (74 treatment, 73 placebo). Peak NSE levels were 47·4 ng/mL (interquartile range [IQR] 22·4–262·6) in the treatment group and 53·3 ng/mL (IQR 26·6–244·2) in the placebo group (median difference −5·9 ng/mL; 95% confidence interval [CI] −34·5–40·8; p = 0·54). ITT sensitivity findings were consistent (geometric mean ratio 0·94; 95% CI 0·61–1·46; p = 0·80). At 180 days, survival (63·5% vs 69·9%) and good neurological outcome (54·1% vs 56·2%) were similar. Serious adverse events were comparable in the ITT population (52·5% vs 50·0%), with none deemed related to the study medication. Interpretation: Early administration of hydrocortisone, ascorbic acid, and thiamine did not reduce neuronal injury or improve 6-month clinical outcomes. The findings do not support empiric neuroprotective use in comatose OHCA survivors. Funding: National Research Foundation of Korea and Korea Health Technology R&D Project.

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