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

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.