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

Cardiac arrest acyl-ghrelin cognitive outcome neuroprotection psychosocial outcomes

Journal

European heart journal. Acute cardiovascular care
ISSN: 2048-8734
Titre abrégé: Eur Heart J Acute Cardiovasc Care
Pays: England
ID NLM: 101591369

Informations de publication

Date de publication:
24 Oct 2024
Historique:
received: 19 08 2024
revised: 27 09 2024
accepted: 22 10 2024
medline: 24 10 2024
pubmed: 24 10 2024
entrez: 24 10 2024
Statut: aheadofprint

Résumé

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

Sections du résumé

BACKGROUND 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 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 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 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 BACKGROUND
Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.

Identifiants

pubmed: 39445445
pii: 7833600
doi: 10.1093/ehjacc/zuae119
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

H B van der Worp (HB)
A J C Slooter (AJC)
M van Smeeden (M)
E Wilms (E)
Martin Rinket (M)
Tim Krol (T)
Rosalie Visser (R)
Esther van Veen (E)
Lucien Gijsbers (L)
Manon Fleuren-Janssen (M)
Michel Kreijtz (M)
Hester Tamminga (H)
Margreet Filius (M)
Martin Rinket (M)
Tim Krol (T)
Wim Addink (W)
Rob Damink (R)
Marlies Snoek-Pecht (M)
Michel Kreijtz (M)
Hester Tamminga (H)
Suzanne Dittrich (S)
Margriet Bosma (M)
Jerôme Appeldoorn (J)
Jolanda Elenbaas (J)
Vera IJmker (V)
Laura de Bever (L)
Ozzy Roesink (O)

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

Auteurs

P C W van Gils (PCW)

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Limburg Brain Injury Center, Maastricht University, Maastricht, the Netherlands.

S Nutma (S)

Department of Clinical Neurophysiology, Technical Medical Center, University of Twente, Enschede, the Netherlands.
Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands.

K F Meeske (KF)

Department of Medical Psychology, Medisch Spectrum Twente, Enschede, the Netherlands.

C van Heugten (C)

Limburg Brain Injury Center, Maastricht University, Maastricht, the Netherlands.
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.

W M van den Bergh (WM)

Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

N A Foudraine (NA)

Department of Critical Care, VieCuri Medical Center, Venlo, the Netherlands.

J le Feber (J)

Department of Clinical Neurophysiology, Technical Medical Center, University of Twente, Enschede, the Netherlands.

P M G Filius (PMG)

Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, the Netherlands.

M J A M van Putten (MJAM)

Department of Clinical Neurophysiology, Technical Medical Center, University of Twente, Enschede, the Netherlands.
Department of Neurology, Medisch Spectrum Twente, Enschede, the Netherlands.

A Beishuizen (A)

Department of Critical Care, Medisch Spectrum Twente, Enschede, the Netherlands.

J Hofmeijer (J)

Department of Clinical Neurophysiology, Technical Medical Center, University of Twente, Enschede, the Netherlands.
Department of Neurology, Rijnstate Hospital, Arnhem, the Netherlands.

Classifications MeSH