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

• 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 (R) 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. 

Ämnesord

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Anesthesiology and Intensive Care  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Anestesi och intensivvård  (hsv)

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Neurology  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Neurologi  (hsv)

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Cardiac and Cardiovascular Systems  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Kardiologi  (hsv)

Genre

government publication  (marcgt)

Indexterm och SAB-rubrik

Cardiac arrest

Brain injury markers

Neurofilament light

NFL

Total-tau

glial fibrially acidic protein

GFAP

S100

Neuron specific enolase

NSE

Prognostication

outcome

biomarkers

Protocol