Zi-Ai Zhao ¹ Hai-Zhou Hu ¹ Wei Li ¹ Jing Qiu ¹ Yong-Gang Zhao ¹ Thanh N. Nguyen ² Hui-Sheng Chen ^1*

• ¹ General Hospital of Northern Theater Command, Shenyang, China
• ² Boston Medical Center, Boston, Massachusetts, United States

Clinically ineffective reperfusion refers to the mismatch between successful reperfusion and favorable functional outcome among large vessel occlusion (LVO) stroke after endovascular treatment (EVT). INSIST-CT (Improving Neuroprotective Strategy for Ischemic Stroke with Sufficient recanalization after Thrombectomy by intra-arterial Cocktail Therapy) trial aimed to explore the safety, feasibility and efficacy of intraarterial cocktail therapy with argatroban, dexamethasone, and edaravone in patients with sufficient reperfusion after EVT.In this prospective, single arm, pilot study, eligible patients with anterior circulation LVO and sufficient reperfusion after EVT were enrolled in the INSIST-CT trial.Concurrent patients who met inclusion/exclusion criteria were retrospectively included as control group. In INSIST-CT group, argatroban, dexamethasone and edaravone was continuously administered for 30 minutes in the culprit artery after sufficient recanalization. The primary endpoint was the proportion of favorable functional outcome, defined as a modified Rankin Scale 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.Thirty patients were enrolled in INSIST-CT group and 261 patients were included in the control group. The proportion of 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, P=0.67; adjusted OR 1.42, 95% CI 0.62-3.26, P=0.41). No significant difference in sICH at 48 hours after treatment was observed between the two groups (unadjusted OR 0.96, 95% CI 0.15-3.56, P=0.96; adjusted OR 0.82 95% CI 0.17-3.97, P=0.809). Similar results were observed after PSM and IPTW analyses.Among anterior circulation LVO patients with sufficient reperfusion after EVT, bridging intra-arterial cocktail therapy composed of argatroban, dexamethasone and edaravone may be safe and feasible, but did not improve 90-day functional outcomes.A numerically higher probability of favorable outcome in INSIST-CT group may suggest potential promise of this cocktail therapy to reduce clinically ineffective reperfusion.