Intra-Arterial Alteplase After Thrombectomy in Basilar Occlusion

Key Takeaways

• Adjunct intra-arterial alteplase was not associated with better 90-day functional independence after successful thrombectomy for basilar artery occlusion.
• Symptomatic intracranial hemorrhage and 90-day mortality were similar between groups.
• The trial stopped early for futility, subgroup analyses were consistent, and angiographic eTICI improvement was seen as a secondary finding.

The IAT-TOP randomized clinical trial compared adjunct intra-arterial alteplase with no intra-arterial thrombolysis after successful reperfusion. Adjusted relative risk for modified Rankin Scale 0 to 2 was 0.93, with 95% CI 0.73 to 1.18 and P = .55. The trial did not show an improvement in 90-day functional outcome.

The study was a multicenter, prospective, randomized, open-label, blinded-end point trial conducted at 30 comprehensive stroke centers in China. Adults presented within 24 hours of the time last known well with acute basilar artery occlusion and were randomized only after successful EVT reperfusion was confirmed. Researchers enrolled 247 patients, excluded 1 after basilar artery reocclusion before alteplase, and analyzed 246 patients, with 124 in the alteplase group and 122 in the control group. The comparison focused on adjunct treatment after thrombectomy rather than the initial reperfusion strategy.

Alteplase was given at 0.225 mg/kg, to a maximum of 22.5 mg, at a concentration of 1.0 mg/mL. Investigators infused the drug distal to the origin of the posterior inferior cerebellar artery. Treatment was to start within 30 minutes after randomization and finish within 15 minutes unless otherwise indicated. The primary efficacy endpoint was modified Rankin Scale 0 to 2 at 90 days. Primary safety endpoints were symptomatic intracranial hemorrhage within 48 hours and all-cause mortality at 90 days.

The primary endpoint was similar between groups. Modified Rankin Scale 0 to 1 occurred in 37.1% versus 39.3%, with adjusted RR 0.94, 95% CI 0.70 to 1.25, and P = .66. Modified Rankin Scale 0 to 3 occurred in 49.2% versus 53.3%, with adjusted RR 0.94, 95% CI 0.77 to 1.16, and P = .58. Ordinal modified Rankin Scale shift was neutral, with adjusted OR 1.00, 95% CI 0.62 to 1.59, and P = .99. Improved eTICI score after intra-arterial thrombolysis was seen in the alteplase group in 10.5% overall and 27.7% when baseline eTICI 3 cases were excluded.

In safety analyses, symptomatic intracranial hemorrhage occurred in 2.4% versus 2.5%, and 90-day mortality occurred in 29.6% versus 27.0%. Adjusted hazard ratio for mortality was 1.07 with 95% CI 0.71 to 1.61 and P = .75. Any intracranial hemorrhage was 4.0% versus 4.1%, while systemic hemorrhagic complications and nonhemorrhagic serious adverse events were similar. The trial was terminated early for futility, and prespecified subgroup analyses did not show evidence of effect modification. Overall, adjunct intra-arterial alteplase was not associated with improved 90-day functional outcomes and had similar reported safety outcomes.