Intra-Arterial Thrombolysis After SUCCESSful Reperfusion in Anterior Circulation Ischemic Stroke

Prospective phase 3 multicenter with open label blinded endpoint (PROBE) superiority randomized controlled trial, with health-economics evaluation.

The study strategy is to demonstrate the superiority of adjunct intra-arterial thrombolysis compared to no adjunct intra-arterial thrombolysis after successful angiographic reperfusion (eTICI 2b-2c-3) after intravenous alone, bridging therapy, or mechanical thrombectomy alone on 90-day functional outcome rate (shift of 90-day modified Rankin Scale toward a better functional outcome).

Patients with anterior circulation large vessel occlusion stroke will be recruited in the angiosuite by neurologists and/or neuroradiologists in participating centres after acute reperfusion therapy (intravenous thrombolysis alone, bridging therapy, or mecanical thrombectomy alone).

Patients enrolled in the experimental arm will receive intra-arterial thrombolysis with Alteplase. The dose of intra-arterial Alteplase is 0.225 mg/kg body weight and the maximal allowed dose is 20mg. Intra-arterial Alteplase will be injected through the guiding catheter placed in the internal carotid artery during 15 minutes.The total intra-arterial dose must be injected in the absence of complications.

Secondary objectives:

• To assess the clinical and safety of adjunct intra-arterial thrombolysis.
• To assess the cost-effectiveness of adjunct intra-arterial thrombolysis.
• To assess the budget impact of new stroke management strategy in case of successful angiographic reperfusion.

Inclusion criteria

• Age ≥ 18 years
• Pre-stroke mRS 0-2
• Acute ischemic stroke with anterior circulation large vessel occlusion defined as intracranial internal carotid artery, M1, or M2 occlusion proven on CT or MRI
• NIHSS score ≥ 5 at admission
• Acute reperfusion strategy started within 24h after stroke onset according to the international guidelines
• DWI-ASPECTS ≥ 2 (MRI) or CT-ASPECTS ≥ 3
• Delay from imaging to puncture within 3 hours for transferred patients
• eTICI 2b-2c-3 after intravenous thrombolysis alone, bridging therapy, or mechanical thrombectomy alone and confirmed by catheter angiogram
• Person affiliated to or beneficiary of a social security plan

Exclusion criteria

• Person who do not speak French
• Contraindications for intra-arterial thrombolysis: Platelet count <100 000/mm3, INR >1.7, AOD use <48h or biological confirmation of activity and effective heparin treatment
• Bleeding-risk complications during the mechanical thrombectomy procedure (e.g carotid dissection, complicated femoral approach)
• Bleeding-risk complications consecutive to a fall associated with stroke
• More than 5 thrombectomy device
• Intracerebral hemorrhage
• Occlusion or high grade stenosis treated by stenting
• Patient expected to be unable to present or be available for 3-month visit follow-up
• Participation in another clinical trial within 30 days prior to the inclusion which the experiment may affect the 90-day mRS score
• Woman of childbearing age without effective contraception
• Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the French Public Health Code