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

Moseby-Knappe, Marion LU ; Levin, Helena LU ; Blennow, Kaj LU ; Ullén, Susann ; Zetterberg, Henrik LU ; Lilja, Gisela LU ; Dankiewicz, Josef LU orcid ; Jakobsen, Janus Christian ; Lagebrant, Alice LU orcid and Friberg, Hans LU , et al. (2022) In Resuscitation Plus 10.
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),... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain injury markers, Cardiac arrest, GFAP, S100, Neurofilament light, Neuron specific enolase, NFL, NSE, Prognostication, outcome, biomarkers, Protocol, Total-tau, glial fibrially acidic protein
in
Resuscitation Plus
volume
10
article number
100258
publisher
Elsevier
external identifiers
  • pmid:35677835
  • scopus:85131451730
ISSN
2666-5204
DOI
10.1016/j.resplu.2022.100258
language
English
LU publication?
yes
id
e6d245d2-19ba-432b-95b2-bbf93a82e0d7
date added to LUP
2023-01-13 10:30:39
date last changed
2024-04-18 17:59:28
@article{e6d245d2-19ba-432b-95b2-bbf93a82e0d7,
  abstract     = {{<p>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.</p>}},
  author       = {{Moseby-Knappe, Marion and Levin, Helena and Blennow, Kaj and Ullén, Susann and Zetterberg, Henrik and Lilja, Gisela and Dankiewicz, Josef and Jakobsen, Janus Christian and Lagebrant, Alice and Friberg, Hans and Nichol, Alistair and Ainschough, Kate and Eastwood, Glenn M. and Wise, Matt P. and Thomas, Matthew and Keeble, Thomas and Cariou, Alain and Leithner, Christoph and Rylander, Christian and Düring, Joachim and Bělohlávek, Jan and Grejs, Anders and Borgquist, Ola and Undén, Johan and Simon, Maryline and Rolny, Vinzent and Piehler, Alex and Cronberg, Tobias and Nielsen, Niklas}},
  issn         = {{2666-5204}},
  keywords     = {{Brain injury markers; Cardiac arrest; GFAP, S100; Neurofilament light; Neuron specific enolase; NFL; NSE; Prognostication, outcome, biomarkers; Protocol; Total-tau, glial fibrially acidic protein}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Resuscitation Plus}},
  title        = {{Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators}},
  url          = {{http://dx.doi.org/10.1016/j.resplu.2022.100258}},
  doi          = {{10.1016/j.resplu.2022.100258}},
  volume       = {{10}},
  year         = {{2022}},
}