Multi-center, randomized, parallel-group, superiority study to compare the efficacy of adjunct intra-arterial rt-PA versus not adjunct intra-arterial rt-PA in the improvement of the efficacy of mechanical thrombectomy in patients with large vessel occlusion acute ischemic stroke.

Inclusion Criteria:

• Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation (ICA, ACA or MCA) treated with MT resulting in a mTICI score 2b/3 at end of the procedure. Patients with a mTICI score 2b/3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.
• Estimated delay to onset of rescue intraarterial rt-PA administration <24 hours from symptom onset, defined as the point in time the patient was last seen well.
• No significant pre-stroke functional disability (modified Rankin scale 0-1), or mRS >1 that according to the investigator is not related to neurological disease (i.e., amputation, blindness)
• Age ≥18
• ASPECTS >6 on non-contrast CT (NCCT) scan if symptoms lasting <4.5 hours of last seen well. In patients with >4.5h of last seen well, a CT-perfusion (Flow maps) or MRI-perfusion should be considered instead of NCCT, especially if >9h have elapsed, or in seriously ill patients (i.e., NIHSS>17). Nonetheless, if a perfusion study is not available, NCCT can still be used as long as it is confirmed without a doubt that the ASPECTS is > 6.
• Informed consent, obtained from patient or acceptable patient surrogate, or Differed Informed Consent (DIC) to avoid any delay in the initiation of the mechanical thrombectomy and the i.a thrombolysis. The DIC will be signed by the patient or acceptable patient surrogate at any time after the tPA treatment is started.

Exclusion Criteria:

• NIHSS score on admission >25
• Contraindication to IV t-PA as per local national guidelines (except time to therapy)
• Use of carotid artery stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
• Need of more than 3 passes (per vessel) or more than a total of 5 passes (in more than one vessel) to complete the endovascular procedure
• Female who is pregnant or lactating or has a positive pregnancy test at time of admission
• Current participation in another investigation drug or device treatment study
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
• Known coagulopathy, INR > 1.7
• Platelets < 50,000
• Renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30
• Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
• Any hemorrhage on CT/MRI
• Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
• Suspicion of aortic dissection
• Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
• History of life-threatening allergy (more than rash) to contrast medium
• SBP >185 mmHg or DBP >110 mmHg refractory to treatment
• Serious, advanced, terminal illness with anticipated life expectancy < 6 months
• Pre-existing neurological or psychiatric disease that would confound evaluation
• Presumed vasculitis or septic embolization
• Unlikely to be available for 90-day follow-up (i.e., no fixed home address, visitor from overseas)

Deidentified individual participant data on outcome measures will be published along with the main results of the trial.

The data will become available after publication of main study results.

The IPD will be available from the Sponsor of the trial on reasonable request.

The evaluation of the primary outcome measure (modified Rankin Scale Score 0-1 at day 90) will be conducted by central blinded evaluators following a structured questionnaire. The evaluation of imaging outcome measures will be conducted at the Imaging Central Core Laboratory by blinded evaluators