Intra-arterial TNK Following Successful EVT in Patients With Large Vessel Occlusion AIS

Rationale: Recently, one prospective multicenter RCT reported a potential beneficial effect of intra-arterial alteplase following successful endovascular thrombectomy (EVT) in patients with an acute intracranial large vessel occlusion. In 2018, another prospective multicenter RCT supported the superiority of tenecteplase over alteplase in ischemic stroke patients with large vessel occlusion.Objective: To assess the effect of EVT in addition to intra-arterial tenecteplase compared to EVT alone, in patients with large vessel occlusion, on functional and safety outcomes.Study design: This is a parallel group, randomized clinical trial of EVT with IA-TNK versus EVT. The trial has observer blind assessment of the primary outcome and of neuro-imaging at baseline and follow-up.Study population: Patients with acute intracranial large vessel occlusion and an eTICI 2b-3 after EVT.Main study parameters/outcomes: The primary effect parameter will be excellent functional status at day 90 defined as a modified Rankin Score (mRS) of 0-1. The estimate will be adjusted for the known prognostic variables age, pre-stroke mRS, time from onset to randomization, stroke severity (NIHSS) and collaterals and adjusted and unadjusted estimates with corresponding 95% confidence intervals will be reported.

Inclusion criteriaAcute ischemic stroke patients with symptomatic intracranial large vessel occlusion (LVO) in the intracranial internal carotid artery, M1 segment of the middle cerebral artery (MCA), a dominant M2 MCA (supplying >55% of the MCA field), intracranial vertebral artery, or basilar artery.Treated with endovascular thrombectomy (EVT) resulting in an eTICI score 2b50/3 at end of the procedure.Age of 18 years or older;National Institutes of Health Stroke Scale (NIHSS) score on admission≥6;Limited Ischemic Burden defined as following: Anterior Circulation Occlusions: ASPECTS ≥ 6 on non-contrast CT or ≥ 5 on MRI-DWI; Posterior Circulation Occlusions: ASPECTS ≥ 6 on CTA-Source Images/MRI-DWI.Time from symptom onset to randomization<24 hours, defined as the point in time the patient was last seen well;Written informed consent.Exclusion criteriaPre-existing dependency with mRS >1;Contraindication to Intravenous Thrombolysis (except time to therapy);Complete clinical recovery in the angiography suite by end of EVT procedure;Use of acute carotid or intracranial stent requiring dual antiplatelet therapy;Pregnancy; if a woman is of childbearing potential a urine or serum beta HCG test is positive;Severe contrast allergy or absolute contraindication to iodinated contrast;Participation in other investigational drug or device clinical trials;Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs;Known genetic or acquired bleeding diathesis, lack of anticoagulant factors, or oral anticoagulant drugs and INR > 1.7, or treated with direct oral anticoagulant agents in the prior 48 hours;platelets <100 000/mm3, aPTT >40 s, or PT >15 s; Blood glucose < 2.7 or >22.2 mmol/L;Severe renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30, or patient requires hemodialysis or peritoneal dialysis;Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal;Suspicion of aortic dissection;Presumed vasculitis or septic embolization;Life expectancy < 1 year;Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.)；CT/MR shows intracranial hemorrhage;Ischemic stroke within 3 months;Severe head trauma within 3 months.