Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: a one-year follow-up of cognitive and psychosocial outcomes

P C W van Gils; S Nutma; K F Meeske; C van Heugten; W M van den Bergh; N A Foudraine; J le Feber; P M G Filius; M J A M van Putten; A Beishuizen; J Hofmeijer; GRECO investigators

doi:10.1093/ehjacc/zuae119

Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: a one-year follow-up of cognitive and psychosocial outcomes

Eur Heart J Acute Cardiovasc Care. 2024 Oct 24:zuae119. doi: 10.1093/ehjacc/zuae119. Online ahead of print.

Authors

P C W van Gils^{1

2}, S Nutma^{3

4}, K F Meeske⁵, C van Heugten^{2

6}, W M van den Bergh⁷, N A Foudraine⁸, J le Feber³, P M G Filius⁹, M J A M van Putten^{3

4}, A Beishuizen¹⁰, J Hofmeijer^{3

11}; GRECO investigators

Affiliations

¹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
² Limburg Brain Injury Center, Maastricht University, Maastricht, the Netherlands.
³ Department of Clinical Neurophysiology, Technical Medical Center, University of Twente, Enschede, the Netherlands.
⁴ Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands.
⁵ Department of Medical Psychology, Medisch Spectrum Twente, Enschede, the Netherlands.
⁶ Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
⁷ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁸ Department of Critical Care, VieCuri Medical Center, Venlo, the Netherlands.
⁹ Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, the Netherlands.
¹⁰ Department of Critical Care, Medisch Spectrum Twente, Enschede, the Netherlands.
¹¹ Department of Neurology, Rijnstate Hospital, Arnhem, the Netherlands.

PMID: 39445445
DOI: 10.1093/ehjacc/zuae119

Abstract

Background: Effective treatments to improve brain recovery after cardiac arrest are needed. Ghrelin showed efficacy in experimental models and was associated with lower neuron specific enolase levels in the clinical Ghrelin in Coma (GRECO) trial. Here we present cognitive and psychosocial outcomes at one-year follow-up.

Methods: GRECO was a phase 2 multicenter, double-blind, randomized, placebo-controlled trial in comatose patients after cardiac arrest. The intervention was intravenous acyl-ghrelin 600 μg twice daily or placebo for one week, starting within 12 hours after the arrest. Patients were assessed after one year using cognitive tests and questionnaires measuring participation, health-related quality of life, mood, and caregiver strain. Composite z-scores of the cognitive tests were computed by comparing the scores to those of a norm-population and averaging the tests for memory, attention and executive functioning separately. Groups were compared based on composite z-scores and cutoff scores for psychosocial outcomes.

Results: Of the 160 participants originally included, 66 of the 85 participants who survived to one year after OHCA completed the psychosocial and cognitive follow-up. The intervention group scored numerically higher across all cognitive domains compared to the control group, but the differences were not statistically significant (memory median = -.850 vs. -1.385, U = 424.5, p = .587; attention median = -.733 vs. -.717, U = 420.5, p = .548; executive functioning median = -.311 vs. -.369, U = 408.5, p = .323). There were significantly fewer signs of depression in the intervention group, U = 322.5, p = .014.

Conclusions: This predefined secondary analysis found that ghrelin treatment was associated with non-significantly but consistently better cognitive outcomes and significantly fewer signs of depression. This is in line with the primary outcomes.

Trial registration: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

Keywords: Cardiac arrest; acyl-ghrelin; cognitive outcome; neuroprotection; psychosocial outcomes.