Neuroprotection via optimizing cerebral blood flow after cardiac arrest (neuro-intact) study - A phase II proof-of-concept study protocol.

INTRODUCTION

Optimizing cerebral blood flow after return of spontaneous circulation (ROSC) is key to neuroprotection in out-of-hospital cardiac arrest (OHCA) patients. Randomized trials comparing fixed mean arterial pressure (MAP) targets have been uniformly neutral, as between- and within-patient heterogeneity in cerebral autoregulation renders uniform targets inadequate. An individualized blood pressure strategy targeting patient-specific cerebral perfusion may reduce secondary brain injury.

METHODS

NEUROprotectIoN via optimizing cerebral blood flow afTer cArdiaC arresT (NEURO-INTACT) is a single-center, single-arm, phase II proof-of-concept trial enrolling 49 comatose OHCA survivors within 12 h post-ROSC. With constant ventilatory settings and continuous electrographic, pulse oximeter and end-tidal carbon dioxide monitoring, MAP is actively manipulated via vasopressor titration to generate slow MAP fluctuations. Changes in cerebral oxygenation (near-infrared spectroscopy) and blood flow velocities (transcranial Doppler) are continuously correlated with MAP by ICM+ software to characterize each patient's cerebral autoregulation and derive an individualized optimal MAP (MAPopt). MAP is then actively titrated to MAPopt, with this assess-and-titrate cycle repeated at three timepoints across 72 h post-ROSC. Primary endpoint is the mean change in neuron-specific enolase from baseline to 72 h. Secondary endpoints include peak cardiac and renal injury biomarkers within 72 h, neurological outcome at discharge, and health-related quality of life at six months, compared against historical controls.

CONCLUSION

This study will explore the effect of individualized, autoregulation-guided hemodynamic management on a validated surrogate marker of brain injury, demonstrate protocol feasibility and safety, and generate effect-size estimates to inform a definitive multicenter trial.

Trial registration: ClinicalTrials.gov ID NCT05679739.