Biomarkers of Brain Injury After Cardiac Arrest; a Statistical Analysis Plan from the TTM2 Trial Biobank Investigators

Overview

Journal Resusc Plus

Date 2022 Jun 9

PMID 35677835

Authors

Marion Moseby-Knappe

Helena Levin

Kaj Blennow

Susann Ullen

Henrik Zetterberg

Gisela Lilja

Josef Dankiewicz

Janus Christian Jakobsen

Alice Lagebrant

Hans Friberg

Alistair Nichol

Kate Ainschough

Glenn M Eastwood

Matt P Wise

Matthew Thomas

Thomas Keeble

Alain Cariou

Christoph Leithner

Christian Rylander

Joachim During

Jan Belohlavek

Anders Grejs

Ola Borgquist

Johan Unden

Maryline Simon

Vinzent Rolny

Alex Piehler

Tobias Cronberg

Niklas Nielsen

Affiliations

Soon will be listed here.

Abstract

Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation.

Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument.

Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities.

Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.

Citing Articles

Predictive Performance of Neuron-Specific Enolase (NSE) for Survival after Resuscitation from Cardiac Arrest: A Systematic Review and Meta-Analysis.

Kurek K, Swieczkowski D, Pruc M, Tomaszewska M, Cubala W, Szarpak L J Clin Med. 2023; 12(24).

PMID: 38137724 PMC: 10744223. DOI: 10.3390/jcm12247655.

Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest: Rationale and design of the prospective TTM2-CT-substudy.

Lang M, Leithner C, Scheel M, Kenda M, Cronberg T, During J Resusc Plus. 2022; 12:100316.

PMID: 36267356 PMC: 9576971. DOI: 10.1016/j.resplu.2022.100316.

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