NEUROprotection Via optimizINg Cerebral Blood Flow afTer cArdiaC arresT (NEURO-INTACT) Study

This single-center proof of concept study aims to assess the efficacy of a blood pressure strategy targeting person- and time-specific cerebral blood flow compared with standard-of-care using neuron-specific enolase as a quantitative biomarker of brain injury. Our central hypothesis is that an individualized blood pressure strategy targeting cerebral perfusion will reduce the extent of brain injury as indicated by changes in levels of neuron-specific enolase from baseline at 72 hours. To test this hypothesis, we will recruit 49 patients to an individualized blood pressure management strategy targeting cerebral blood flow, where optimal blood pressure will be serially calculated by the ICM+ brain monitoring software (Cambridge, UK) using inputs from transcranial Doppler ultrasound and near-infrared spectroscopy.

Study Overview

• Status: Recruiting
• Conditions: Out-Of-Hospital Cardiac Arrest (OHCA)
• Intervention / Treatment: Other: Individualized blood pressure strategy

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shir Lynn Lim; Phone Number: 69082222; Email: shir_lynn_lim@nuhs.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Heart Centre, Singapore
    • Contact: Shir Lynn Lim; Phone Number: 69082222; Email: shir_lynn_lim@nuhs.edu.sg
    • Principal Investigator: Shir Lynn Lim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 21 years of age
2. Comatose defined as not being able to obey verbal commands and no verbal response to pain after sustained ROSC.

Exclusion Criteria:

1. ≥ 80 years old at time of enrolment
2. Pregnant patients
3. Limitations of care or life support therapy withdrawn within 24 hours of admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized blood pressure strategy; Hemodynamic optimization performed to an individualized target mean arterial pressure in the first 72 hours post ROSC based on cerebral perfusion assessed serially.	Other: Individualized blood pressure strategy; An individualized blood pressure strategy targeting cerebral blood flow, serially guided by near-infrared spectroscopy and transcranial Doppler ultrasound. Assessments are performed on admission, and at 12, 24 and 48 hours post-ROSC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in neuron-specific enolase (NSE)	The mean change in concentration of NSE from baseline levels to 72 hours post-ROSC.	72 hours post ROSC

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak concentration of myocardial injury biomarker - High-sensitive troponin (hsTNT)	Peak concentration of myocardial injury biomarker, High-sensitive troponin (hsTNT) within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of myocardial injury biomarker - N-terminal pro b-type natriuretic peptide (NT-proBNP)	Peak concentration of myocardial injury biomarker, N-terminal pro b-type natriuretic peptide (NT-proBNP) within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of renal function - Creatinine	Peak concentration of renal function, Creatinine within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of renal injury biomarker - Proenkephalin A 119-159 (penKID)	Peak concentration of renal injury biomarker, Proenkephalin A 119-159 (penKID) within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of renal injury biomarker - Biologically active adrenomedullin (bio-ADM)	Peak concentration of renal injury biomarker, Biologically active adrenomedullin (bio-ADM) within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of renal injury biomarker - Tissue inhibitor of metalloproteinases 2 (TIMP2)	Peak concentration of renal injury biomarker, Tissue inhibitor of metalloproteinases 2 (TIMP2) within 72 hours of ROSC	Within 72hours of ROSC
Peak concentration of renal injury biomarker - Insulin Like Growth Factor Binding Protein 7 (IGFBP7)	Peak concentration of renal injury biomarker, Insulin Like Growth Factor Binding Protein 7 (IGFBP7) within 72 hours of ROSC	Within 72hours of ROSC
Neurological outcome	Neurological outcomes measured by Cerebral Performance Category (CPC) scale on hospital discharge, and at 3, 6 and 12 months post OHCA. The CPC purports to assess domains of functioning after cardiopulmonary resuscitation (CPR) with scores ranging from 1 (good cerebral performance/normal life) to 5 (brain death).	Through study completion, average of 12 months post OHCA
Physical function	Physical function measured by the change of Duke Activity Status Index (DASI) self-reported questionnaire on hospital discharge, and at 3, 6 and 12 months post OHCA. DASI score is the sum of the questionnaire responses, score of 34 or less means moderate-to-severe complications.	Through study completion, average of 12 months post OHCA
Neurocognitive outcome - Montreal Cognitive Assessment (MOCA)	Neurocognitive is assessed by Montreal Cognitive Assessment (MOCA, global cognition) on hospital discharge, and at 3, 6 and 12 months post OHCA. Scores on the MOCA from zero to 30, while score of 26 and above is considered normal.	Through study completion, average of 12 months post OHCA
Neuropsychological outcome - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	Neuropsychological deficits is assessed by the modified local version of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) on hospital discharge, and at 3, 6 and 12 months post OHCA. Standard scores of 70 and above will classify as average/mild impairment, scores 55 to 69 as moderate impairment and severe impairment for scores less than 55.	Through study completion, average of 12 months post OHCA
Neuropsychological outcome- Depression, Anxiety, and Stress Scale (DASS-21)	Depression, Anxiety, and Stress Scale (DASS-21) is used to assess neuropsychological outcome on hospital discharge, and at 3, 6 and 12 months post OHCA.	Through study completion, average of 12 months post OHCA
Health-related quality of life	Health-related quality of life measured by EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire on hospital discharge, and at 3, 6 and 12 months post OHCA. EQ-5D-5L questionnaire consists of 5 dimensions (mobility, self care, usual activities, pain/comfort, anxiety/depression). There are 5 levels in each dimensions. The lowest level means normal which the highest level means extremely severe.	Through study completion, average of 12 months post OHCA

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome - Digital neurocognitive assessment	Neurocognitive is assessed by digital neurocognitive assessment on hospital discharge, and at 3, 6 and 12 months post OHCA.	Through study completion, average of 12 months post OHCA

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Shir Lynn Lim, National University Hospital, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 30, 2022
• First Submitted That Met QC Criteria: December 23, 2022
• First Posted (Actual): January 11, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: NEURO-INTACT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No