Cracking Coma: Towards EEG and MRI Based Precision Medicine After Cardiac Arrest

NCT03308305 | Completed

• 1 other identifier: 2017-1006
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 3

Brief Summary

Rationale: 30-70% of comatose patients admitted to the intensive care unit (ICU) after cardiac arrest never regain consciousness as a result of post anoxic encephalopathy (PAE). Early identification of patients without potential for recovery of brain functioning may prevent inappropriate continuation of medical treatment and improve communication between doctors and patients. However, current diagnostic and prognostic measures can identify only 20-50% of the patients with irreversible brain damage, precluding cerebral recovery and awakening. Also, the pathophysiology of brain damage is largely unclear. New magnetic resonance imaging (MRI) sequences hold potential to substantially improve outcome prediction. Objectives: 1. To estimate the additional value of early MRI monitoring for the prediction of neurological outcome of comatose patients after cardiac arrest. 2. To gain insight in the pathophysiology of PAE by associating MRI findings with histopathological studies of brain tissue obtained from non-survivors. Study design: prospective cohort study. Study population: 100 subsequent comatose patients after cardiac arrest, admitted to the ICU. Intervention: In addition to standard treatments, patients will undergo MRI of the brain at day 3, 7, and three months after cardiac arrest. A subgroup of patients will be scanned within 24 hours after cardiac arrest, to assess feasibility and to gain more insight in the evolution of brain damage in PAE. Survivors will be followed for one year. Outcome measurements will focus on disabilities, quality of life, and depression. MRI measures will be related to outcome. Main study parameters/endpoints: The primary outcome measure is neurological outcome, defined as the score on the Cerebral Performance Category (CPC) at six months, dichotomized as good (CPC 1-2 = no or moderate neurological disability) or poor (CPC 3-5 = severe disability, coma, or death). Secondary outcome measures include cognitive functioning, depression, and quality of life at one year, as well as histopathological damage of brain tissue of non-survivors.

Conditions

Post-Anoxic Coma; Postanoxic Enchephalopathie

Keywords

Coma; Cardiac arrest; Prognosis; MRI; EEG

Outcome Measures

Primary Outcomes (1)

• Functional outcome

  Functional outcome as defined on the Cerebral Performance Category , dichotomized as good (CPC 1-2 = no or moderate neurological disability) or poor (CPC 3-5 = severe disability, coma, or death)

  6 months after cardiac arrest

Secondary Outcomes (6)

• cognitive functioning as defined by professional Neuropsychological examination

  12 months after cardiac arrest

• Presence of depression

  12 months after cardiac arrest

• histopathological damage of brain tissue of non-survivors

  Autopsy will take place at the first workday after the patient died at the ICU after cardiac arrest. After 2 weeks, the brain will be cut and paraffine coupes will be made. Analyses of the coupes will take place in batches.

• Early functional outcome

  At discharge from the ICU and 3 months after cardiac arrest.

• Participation in society score

  12 months after cardiac arrest

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of one hundred adult, comatose patients, successfully resuscitated from cardiac arrest. Generally, these patients are predominantly male and approximately 60-65 years of age. The patients are by definition at least temporarily incapacitated.

You may qualify if:

• Comatose, defined as Glasgow Coma Score ≤ 8
• Age ≥ 18 years
• Cardiac arrest with a presumed cardiac cause of the arrest or caused by pulmonary embolism
• Admission to ICU

You may not qualify if:

• Pregnancy
• Life expectancy \< 24 hours
• Absence of written informed consent (by a legal representative)
• Pre-existing dependency in daily living, defined as CPC score 3 or 4
• Any known progressive brain illness, such as a brain tumor or neurodegenerative disease.
• Known contra-indication for MRI

Sponsors & Collaborators

• Rijnstate Hospital: lead
• Donders Centre for Cognitive Neuroimaging: collaborator
• Maastricht University Medical Center: collaborator
• University Medical Center Nijmegen: collaborator

Study Sites (3)

Rijnstate Hospital

Arnhem, Gelderland, 6815 AD, Netherlands

Location

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Related Publications (4)

• Verhulst MMLH, Keijzer HM, van Gils PCW, van Heugten CM, Meijer FJA, Tonino BAR, Bonnes JL, Delnoij TSR, Hofmeijer J, Helmich RC. Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors. Hum Brain Mapp. 2024 Oct 15;45(15):e26769. doi: 10.1002/hbm.26769.

  PMID: 39449030 RESULT

• Keijzer HM, Duering M, Pasternak O, Meijer FJA, Verhulst MMLH, Tonino BAR, Blans MJ, Hoedemaekers CWE, Klijn CJM, Hofmeijer J. Free water corrected diffusion tensor imaging discriminates between good and poor outcomes of comatose patients after cardiac arrest. Eur Radiol. 2023 Mar;33(3):2139-2148. doi: 10.1007/s00330-022-09245-w. Epub 2022 Nov 24.

  PMID: 36418623 RESULT

• Keijzer HM, Lange PAM, Meijer FJA, Tonino BAR, Blans MJ, Klijn CJM, Hoedemaekers CWE, Hofmeijer J, Helmich RC. MRI markers of brain network integrity relate to neurological outcome in postanoxic coma. Neuroimage Clin. 2022;36:103171. doi: 10.1016/j.nicl.2022.103171. Epub 2022 Aug 26.

  PMID: 36058165 RESULT

• Keijzer HM, Verhulst MMLH, Meijer FJA, Tonino BAR, Bosch FH, Klijn CJM, Hoedemaekers CWE, Hofmeijer J. Prognosis After Cardiac Arrest: The Additional Value of DWI and FLAIR to EEG. Neurocrit Care. 2022 Aug;37(1):302-313. doi: 10.1007/s12028-022-01498-z. Epub 2022 Apr 25.

  PMID: 35469391 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Of patients who die during ICU stay, families are asked permission for autopsy of the brain. After fixation, multiple fragments of brain tissue will be retained for analysis.

MeSH Terms

Conditions

Coma; Heart Arrest

Condition Hierarchy (Ancestors)

Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Study Officials

• J Hofmeijer, PhD

  Rijnstate Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 12, 2017
• Study Start: June 11, 2018
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)