NCT03308305

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

Completed Last updated 30 January 2026

What this trial tests

trial in Post-Anoxic Coma in 94 participants. Completed in 1 November 2025.

Timeline

11 June 2018

Primary endpoint
1 November 2025

1 November 2025

Quick facts

Lead sponsor	Rijnstate Hospital
Status	Completed
Study type	OBSERVATIONAL
Enrollment	94
Start date	11 June 2018
Primary completion	1 November 2025
Estimated completion	1 November 2025
Sites	3 locations across Netherlands

Conditions studied

• Post-Anoxic Coma — all drugs for Post-Anoxic Coma →
• Postanoxic Enchephalopathie — all drugs for Postanoxic Enchephalopathie →

Sponsor

Rijnstate Hospital

Who can join

18 and older, any sex, with Post-Anoxic Coma or Postanoxic Enchephalopathie. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Long Term Cognitive Function After Cardiac Arrest: A Mini-Review.
   Hagberg G, Ihle-Hansen H, Sandset EC, Jacobsen D, et al · · 2022 · cited 15× · PMID 35721022 · DOI 10.3389/fnagi.2022.885226
2. MRI markers of brain network integrity relate to neurological outcome in postanoxic coma.
   Keijzer HM, Lange PAM, Meijer FJA, Tonino BAR, et al · · 2022 · cited 12× · PMID 36058165 · DOI 10.1016/j.nicl.2022.103171
3. Free water corrected diffusion tensor imaging discriminates between good and poor outcomes of comatose patients after cardiac arrest.
   Keijzer HM, Duering M, Pasternak O, Meijer FJA, et al · · 2023 · cited 10× · PMID 36418623 · DOI 10.1007/s00330-022-09245-w
4. Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.
   Verhulst MMLH, Keijzer HM, van Gils PCW, van Heugten CM, et al · · 2024 · cited 3× · PMID 39449030 · DOI 10.1002/hbm.26769
5. Separate functional and structural cerebral mechanisms relate to postanoxic coma recovery
   Verhulst MM, Keijzer HM, Mei T, Klijn CJ, et al · · 2025 · DOI 10.1101/2025.08.13.25333575
6. Brain topology and cognitive outcomes after cardiac arrest: A graph theoretical analysis of fMRI data.
   Verhulst MMLH, Lange P, Tuladhar AM, Tewarie P, et al · · 2025 · PMID 40567889 · DOI 10.1016/j.ynirp.2025.100244
7. Predictive value of resting-state fMRI graph measures in hypoxic encephalopathy after cardiac arrest.
   Lange P, Verhulst M, Tuladhar AM, Tewarie P, et al · · 2025 · PMID 40056784 · DOI 10.1016/j.nicl.2025.103763