Arterial Glyceryl Trinitrate in Acute Ischemic Stroke After Thrombectomy for Neuroprotection (AGAIN): A Pilot Randomized Controlled Trial

Abstract

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of glyceryl trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800 μg GTN or the same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends, while non-significant, were noted in both outcome and imaging for functional independence at 90 days and reduction in final infarct volume (75.0% vs 65.0%; 33.2 vs 38.9 ml) for the GTN group. Moreover, the concentration of blood NOx in the GTN group was significantly higher than in the control group at 2 h after GTN administration (26.2 vs 18.0 μmol/l, p < 0.05). The AGAIN study suggests intra-arterial administration of GTN post-endovascular therapy is safe and feasible and GTN successfully raised NOx levels over controls at 2 h. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy.