Intra-arterial tenecteplase fails to improve recovery after basilar artery thrombectomy
Adjunctive intra-arterial tenecteplase did not improve 90-day functional recovery after successful thrombectomy for acute basilar artery occlusion in the INSIST-IT randomized clinical trial, and the study was stopped early because of safety concerns and lack of efficacy. The result matters because basilar artery occlusion remains one of the most dangerous forms of ischemic stroke, with severe disability and high mortality even after reperfusion has been achieved in the proximal vessel.
The trial tested a simple but clinically consequential question: if the clot has been opened mechanically, can local thrombolysis improve downstream perfusion enough to change recovery? In theory, the answer seemed plausible. Reperfusion of the large artery does not guarantee restoration of capillary flow, particularly in the posterior circulation where perforator territories are small, eloquent, and vulnerable to microvascular obstruction. White blood cells, microthrombi, endothelial swelling, and pericyte constriction can leave tissue ischemic despite an angiographically successful result.
Trial design and patient selection
INSIST-IT enrolled patients with acute basilar artery occlusion within 24 hours of estimated symptom onset who achieved successful reperfusion after endovascular treatment. Investigators used a prospective, randomized, adaptive-enrichment, open-label design with blinded endpoint assessment. Patients were assigned in a 1:1 ratio to receive either intra-arterial tenecteplase or standard medical therapy alone after thrombectomy.
A total of 144 patients were randomized: 75 to tenecteplase and 69 to control. Follow-up was completed for 143 participants, a remarkably high retention rate of 99.3%. Even with that strong follow-up, the Data Safety and Monitoring Committee recommended early termination because the accumulating data pointed in the wrong direction on both efficacy and safety.
The primary efficacy endpoint was independent ambulation at 90 days, defined as a modified Rankin Scale score of 0 to 3. The primary safety endpoint was symptomatic intracranial hemorrhage. Those two outcomes capture the central tension in post-thrombectomy rescue therapy: any gain in tissue salvage has to justify the hemorrhagic risk of another thrombolytic exposure.
Functional outcomes stayed flat, and mortality trended higher
At 90 days, independent ambulation was achieved in 40.0% of patients in the tenecteplase group and 50.0% in the control group. The odds ratio was 0.67, with a 95% confidence interval from 0.34 to 1.29, and the P value was 0.23. In plain clinical terms, adjunctive intra-arterial tenecteplase did not improve the chance of walking independently after basilar artery thrombectomy.
The mortality signal moved in the opposite direction. All-cause mortality at 90 days was 41.3% in the tenecteplase group versus 26.5% in controls, with an odds ratio of 1.96 and a 95% confidence interval of 0.97 to 4.03. The P value of 0.063 does not cross a conventional threshold for statistical significance, but the direction of effect is difficult to ignore in a condition where survival itself is a major endpoint.
Symptomatic intracranial hemorrhage occurred in 6.2% of the tenecteplase group and 4.8% of the control group. The odds ratio was 1.31, with a wide 95% confidence interval of 0.28 to 6.89, and the P value was 0.73. The event rates were not dramatically different, but the study stopped early before any signal of benefit could emerge, and the safety review judged the balance unfavorable.
One sentence captures the practical result: adding intra-arterial tenecteplase after successful basilar thrombectomy did not rescue outcomes.
Why the biological rationale did not translate into benefit
The negative result is notable because the rationale was not speculative in a vacuum. Basilar artery occlusion behaves differently from many anterior circulation strokes. The posterior circulation supplies structures with limited collateral buffering, and neurologic deterioration can be abrupt and catastrophic. Even when the main artery is reopened, small-vessel dysfunction may still choke off tissue perfusion in the brainstem and other critical territories.
That mechanistic logic made adjunctive thrombolysis appealing. Tenecteplase, delivered directly into the artery after reperfusion, was meant to work where mechanical thrombectomy cannot: at the level of distal emboli and microcirculatory obstruction. The hope was that local drug delivery would reduce residual clot burden and improve capillary flow without systemic exposure. Instead, the trial did not show a functional advantage, suggesting that the dominant barriers to recovery in this setting may be less amenable to thrombolytic rescue than expected.
The result also fits with the broader uncertainty around translating angiographic success into tissue-level success. Recanalization is not the same as reperfusion, and the no-reflow phenomenon remains a serious problem after apparently complete reopening of the vessel. In basilar artery occlusion, where the margin for error is narrow, a therapy that does not reliably shift downstream perfusion may simply add complexity and bleeding risk without changing the clinical course.
What this means for stroke practice now
For now, the trial pushes intra-arterial tenecteplase out of the category of promising rescue strategy and into the category of an intervention that failed to prove benefit in a randomized setting. The result will matter most to interventional stroke teams deciding what to do immediately after a technically successful thrombectomy in basilar artery occlusion. Routine use of adjunctive intra-arterial tenecteplase is difficult to justify on the basis of these data.
The study also reinforces how different posterior circulation stroke remains from anterior circulation disease. Previous work has suggested potential benefit from adjunctive intra-arterial thrombolysis after thrombectomy in large vessel occlusion of the anterior circulation, including the CHOICE trial and related studies. INSIST-IT shows that those signals cannot be assumed to extend to basilar artery occlusion, where anatomy, collateral patterns, and tissue vulnerability differ in clinically important ways.
The early stop leaves one unresolved issue: whether any subgroup of basilar occlusion patients might still benefit under narrower conditions, such as different infarct burdens, clot features, or reperfusion profiles. The trial does not answer that question, and its premature termination limits the certainty around smaller effect sizes. What it does answer is more immediate: in this randomized cohort, adjunctive intra-arterial tenecteplase did not improve recovery and carried enough concern for the monitoring committee to halt the study before completion.