REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts (REPERFUSE)

REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts

REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts (REPERFUSE)

The main objective is to evaluate the efficacy of IV administration of the P2Y12 inhibitor (cangrelor) in addition to mecanich thrombectomy and WMD versus mecanich thrombectomy and WMD alone on the functional prognosis at 3 months, in patients with acute ischemic stroke eligible for mecanich thrombectomy on the basis of infusion imaging between 0 and 24 hours after the onset of symptoms.

The emergent reperfusion of the ischemic penumbra is the goal of acute ischemic stroke (AIS) treatment. Mechanical thrombectomy (MT) may be proposed up to 6 hours and from 6 to 24 hours after stroke onset if multimodal imaging demonstrates the presence of a substantial ischemic penumbra. Despite the major benefit associated with MT, more than half of patients will remain disabled at 3 months. The rate of complete reperfusion after MT appears to be a major factor affecting functional outcome. However, this rate of complete reperfusion is only achieved in 50 % of the patients due to, at least in part, distal microcirculatory impairment and or erratic emboli. In coronary artery disease, new antiplatelet agents, with a very short half-life, such as P2Y12 inhibitors (P2Y12I), have been shown to reduce in-stent thrombosis, myocardial infarction and death. The IV route for P2Y12 inhibitors administration is adapted to the stroke population who has frequently dysphagia that prevents per os drug administration. In addition, the very short half-life of the drug is quite interesting for the management of hemorrhagic complications or emergent surgical interventions and early antithrombotic secondary prevention initiation. Hpothesis: subgroup of patients treated from 0 to 24 hours after onset with a demonstrated ischemic penumbra on perfusion imaging, the administration of P2Y12I in addition to MT and best medical management (BMM) may increase reperfusion rates and improve functional outcome compared to MT with BMM alone.

treated by P2Y12 inhibitor (cangrelor) in addition to MT and BMM. The dose of cangrelor will be started with a 30 micrograms/kg IV bolus over 1 minute right after randomization and before MT. The bolus will be immediately followed with 4 micrograms/kg/min IV infusion for the duration of MT up to 4 hours. Cangrelor infusion will be stopped at the end of the MT procedure and will not go further 4 hours. Transition to oral antiplatelet therapy will be possible 1 hour after cangrelor infusion discontinuation. No other anti-thrombotic drug is authorized during cangrelor infusion. MT technique choice is left to the investigator decision.

treated by BMM associated to MT. Anti-thrombotic including alteplase are authorized if they follow the recommendations of the international guidelines. If alteplase infusion is given, no other anti-thrombotic drug is allowed for the following 24 hours. MT technique choice is left to the choice of the investigator.

Favorable functional evaluation at 3 month for patients with acute ischemic strocke treated by cangrelor.

The favorable functional outcome at 3 month will be evaluated using a modified Rankin Scale (mRS). The scale runs from 0 to 6, running from perfect health without symptoms to death (0: no symptoms, 3: Moderate disability. Requires some help, but able to walk unassisted, 6: Dead).

Inclusion Criteria: Age18 or older Anterior circulation intracanial large artery occlusion proved on angioscanner or angio MRI. Symptoms onset < 24h at imaging Indication for MT and fulfillment of the following brain imaging criteria : Perfusion imaging: An initial infarct volume (ischemic core on DWI or CTP calculated by the RAPID software) of less than 70 ml, a ratio between the critically hypoperfused lesion volume (calculated by RAPID with a TMax>6s) and initial infarct volume of 1.8 or more, and an absolute difference between those 2 volumes of 15 ml or more. OR (if perfusion imaging not available or uninterpretable) : CORE CLINICAL MISMATCH: Core calculated on DWI by RAPID, <25 mL if NIHSS 10-20 and <50 mL id NIHSS>20 Pre-stroke mRS ≤ 2 NIHSS ≥ 6 Exclusion Criteria:- Contraindication to MT Patient over 80 years old with >10 microbleeds on pre-treatment MRI Pre-existing dependency with mRS ≥3. Tandem ICA-MCA occlusions requiring stenting ASPECT<6 on NCCT or DWI-MRI Known hypersensitivity to cangrelor or to any of the excipients (mannitol, sorbitol) History of previous intracranial hemorrhage Evidence of active bleeding or acute trauma (fracture) on examination Recent surgery with a significant risk of bleeding VKA oral anticoagulation with INR >1.7 Curative heparin or direct oral anticoagulants (DOACs) in previous 48 hours Platelet count <100 000/ mm3 Women with childbearing potential (15-49 years old)