Ghrelin for neuroprotection in post-cardiac arrest coma: a 1-year follow-up of cognitive and psychosocial outcomes

Aims: 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 1-year follow-up. Methods and results: GRECO was a Phase 2 multicentre, double-blind, randomized, placebo-controlled trial in comatose patients after cardiac arrest. The intervention was intravenous acyl-ghrelin 600μg twice daily or placebo for 1 week, starting within 12h after the arrest. Patients were assessed after 1 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 with 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 cut-off scores for psychosocial outcomes. Of the 160 participants originally included, 66 of the 85 participants who survived to 1 year after OHCA completed the psychosocial and cognitive follow-up. The intervention group scored numerically higher across the cognitive domains compared with the control group, but the differences were not statistically significant (memory median = -0.850 vs. -1.385, U = 424.5, P = 0.587; attention median = -0.733 vs. -0.717, U = 420.5, P = 0.548; and executive functioning median = -0.311 vs. -0.482, U = 408.5, P = 0.323). There were significantly fewer signs of depression in the intervention group (U = 322.5, P = 0.014). Conclusion: 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.