Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators

Moseby-Knappe, Marion, Levin, Helena, Blennow, Kaj, Ullén, Susann, Zetterberg, Henrik, Lilja, Gisela, Dankiewicz, Josef, Jakobsen, Janus C., Lagebrant, Alice, Friberg, Hans, Nichol, Alistair, Ainschough, Kate, Eastwood, Glenn M., Wise, Matt P., Thomas, Matthew, Keeble, Thomas R., Cariou, Alain, Leithner, Christoph, Rylander, Christian, Düring, Joachim, Bělohlávek, Jan, Grejs, Anders, Borgquist, Ola, Undén, Johan, Simon, Maryline, Rolny, Vinzent, Piehler, Alex, Cronberg, Tobias and Nielsen, Niklas (2022) Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators. Resuscitation Plus, 10. p. 100258. ISSN 2666-5204

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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.

Item Type: Journal Article
Keywords: cardiac arrest, brain injury markers, neurofilament light, NFL, total-tau
Faculty: Faculty of Health, Education, Medicine & Social Care
Depositing User: Ian Walker
Date Deposited: 21 Jun 2022 10:53
Last Modified: 01 Jul 2022 12:05

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