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Clinical Trial
. 2023 Dec;49(12):1467-1478.
doi: 10.1007/s00134-023-07247-w. Epub 2023 Nov 9.

Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial

Laust E R Obling  1 , Rasmus P Beske  2 , Martin A S Meyer  2 , Johannes Grand  2 , Sebastian Wiberg  2   3 , Benjamin Nyholm  2 , Jakob Josiassen  2 , Frederik T Søndergaard  2 , Thomas Mohr  4 , Anders Damm-Hejmdal  5 , Mette Bjerre  6 , Ruth Frikke-Schmidt  7   8 , Fredrik Folke  5   8   9 , Jacob E Møller  2   8   10 , Jesper Kjaergaard  2   8 , Christian Hassager  2   8
Affiliations
Clinical Trial

Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial

Laust E R Obling et al. Intensive Care Med. 2023 Dec.

Abstract

Purpose: Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients.

Methods: The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up.

Results: We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group.

Conclusion: Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.

Trial registration: ClinicalTrials.gov NCT04624776.

Keywords: Inflammation; Intensive cardiovascular care; Neuroprotection; Out-of-hospital cardiac arrest; Post-cardiac arrest syndrome.

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Conflict of interest statement

The salary of the corresponding author was supported by a grant from the Research Foundation of Rigshospitalet (E-22652-04). The study, inclusive salary of RPB, was supported by a grant from Novo Nordisk Foundation (NNF20OC0064043) in the name of CH. CH is also supported by an unrestricted grant from Lundbeck Foundation (R186-2015–2132), and received a speaker honorarium from Abiomed during the course of the study, and further is a board member of the European Society of Cardiology and serves as chair of the Danish Heart Foundation. JK is supported by an unrestricted grant from Novo Nordisk Foundation (NNF17OC0028706), and is a part of two Data Safety Monitoring Boards for two randomized controlled trials, The IVIO trial (chair) and the COCA trial, without any reimbursement. JEM received two research grants outside the current study from Abiomed and Novo Nordisk Foundation; further he received speaker honorariums from Abiomed, Abbott, and Boehringer Ingelheim, and attended meetings with the support of Abiomed. FF is supported by a research grant from Novo Nordisk Foundation (NNF19OC0055142). RFS received grants from Lundbeck Foundation, Danish Heart Foundation, and Sygeforsikringen Danmark Research Fund, all outside the current study. The remaining authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Consort flow diagram. *Screening was done retrospectively per-protocol through review of data from the Danish Cardiac Arrest Registry. †Based on previous data, patients with PEA as primary rhythm accounted for ~ 5% at our cardiac arrest centers, thus the number of eligible patients with PEA was estimated to 10% of patients with primary shockable rhythm. ‡Erronous inclusions, excluded en-route or upon arrival to hospital
Fig. 2
Fig. 2
Primary efficacy analyses: A Treatment-by-time interaction for IL-6 (pg/mL) depicting geometric means and 95% confidence intervals after antilog to each time point according to randomization; B Treatment-by-time interaction for NSE (ug/L) depicting geometric means and 95% confidence intervals after antilog to each time point according to randomization. The figure includes the measurements for the modified intention-to-treat population (n = 137)
Fig. 3
Fig. 3
Kaplan–Meier plot of survival to day 180 after out-of-hospital cardiac arrest (modified intention-to-treat population), presenting the crude hazard ratio with 95% CI from a univariate Cox regression model, and the hazard ratio with 95% CI from a predefined multivariable Cox regression model adjusted for sex, age, primary defibrillator rhythm, time to ROSC, and primary percutaneous coronary intervention performed
See this image and copyright information in PMC

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