by Isabella Colonna
For June, we have selected Nutma S, Beishuizen A, van den Bergh WM, Foudraine NA, le Feber J, Filius PMG, Cornet AD, van der Palen J, van Putten MJAM, Hofmeijer J; GRECO Investigators. Ghrelin for Neuroprotection in Post-Cardiac Arrest Coma: A Randomized Clinical Trial. JAMA Neurol. 2024 May 6:e241088. doi: 10.1001/jamaneurol.2024.1088. Epub ahead of print. PMID: 38709502; PMCID: PMC11074931.
Our paper of the month reports the result of a phase 2, placebo-controlled, randomised clinical trial investigating the safety and the potential efficacy of intravenous treatment with acyl-ghrelin in improving neurological outcome in patients in a coma after cardiac arrest. Ghrelin is a hormone with an important role in signaling nutrient availability from the gastrointestinal tract to the brain; moreover, it also works as a mildly excitatory neurotransmitter. In preclinical studies, acyl-ghrelin, the bioactive form of ghrelin, has been associated with improved recovery of in vitro neuronal cultures exposed to hypoxia and with reduced post-mortem histological brain damage of rats after cardiac arrest.
In this phase 2 trial, 160 patients in a coma after cardiac arrest were randomly assigned in a ratio of 1:1 to receive acyl-ghrelin at a dose of 600 μg or placebo, administered in an infusion in 30 minutes, twice daily for one week, starting within twelve hours after the cardiac arrest. The primary outcome was any improvement in neurological outcome at 6 months according to the Cerebral Performance Category (CPC) scale, while secondary outcomes were mortality as well as CPC scores at 3 and 12 months. Safety outcomes included any serious adverse events.
At six months after cardiac arrest, there was an improvement over all categories of the CPC in the intervention group, although it did not reach statistical significance (p = 0.06). The incidence and the type of adverse events were similar in the two groups; death occurred in 37% and 51% of patients in the intervention and control groups, respectively (p=0.08).
In conclusion, this study showed that treatment with acyl-ghrelin was safe and had potential benefit in improving neurological outcome in patients in a coma after cardiac arrest. Phase 3 trials are needed for further evidence of efficacy.
