Intra-arterial cocktail therapy for patients with anterior circulation large vessel occlusion who achieved endovascular reperfusion.

BACKGROUND

Clinically ineffective reperfusion (CIR) refers to the discrepancy between successful reperfusion and a favorable functional outcome in patients with large vessel occlusion (LVO) stroke after endovascular treatment (EVT). The Improving Neuroprotective Strategy for Ischemic Stroke with Sufficient Recanalization after Thrombectomy by Intra-arterial Cocktail Therapy (INSIST-CT) trial aimed to explore the safety, feasibility, and efficacy of intra-arterial cocktail therapy using argatroban, dexamethasone, and edaravone in patients who achieved sufficient reperfusion after EVT.

METHODS

In this prospective, single-arm, pilot study, eligible patients with anterior circulation LVO who achieved sufficient reperfusion after EVT were enrolled in the INSIST-CT trial. Consecutive patients who met the inclusion/exclusion criteria were included in the control group retrospectively. In the INSIST-CT group, argatroban, dexamethasone, and edaravone were continuously administered for 30 min into the culprit artery after sufficient recanalization. The primary endpoint was the proportion of favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to account for multiple confounders.

RESULTS

A total of 30 patients were included in the INSIST-CT group, and 261 patients were included in the control group. The proportion of the patients with the primary endpoint was 60% in the INSIST-CT group and 55.9% in the control group (unadjusted odds ratio [OR] 1.18, 95% CI 0.55-2.61,  = 0.67; adjusted OR 1.42, 95% CI 0.62-3.26,  = 0.41). No significant difference in sICH at 48 h after treatment was observed between the two groups (unadjusted OR 0.96, 95% CI 0.15-3.56,  = 0.96; adjusted OR 0.82 95% CI 0.17-3.97,  = 0.809). Similar results were observed after the PSM and IPTW analyses.

CONCLUSION

In anterior circulation, LVO patients who achieved sufficient reperfusion after EVT, bridging intra-arterial cocktail therapy with argatroban, dexamethasone, and edaravone may be safe and feasible. However, it did not improve the 90-day functional outcomes. A numerically higher probability of a favorable outcome in the INSIST-CT group suggests the potential promise of this cocktail therapy in reducing clinically ineffective reperfusion.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov, NCT04202549.