Clinical trial NCT04667078: REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts
Official title: REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts (REPERFUSE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Ischemia
Lead sponsor: Fondation Ophtalmologique Adolphe de Rothschild
Sponsor class: NETWORK
Collaborators: name: Ministry of Health, France
First posted: 2020-12-14
Enrollment: 368
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: experimental group will be treated by P2Y12 inhibitor (cangrelor) in addition to MT and BMM
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Hypothesis: 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.

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Anterior circulation intracanial large artery occlusion isolated (Intracranial ICA and/or MCA) proved on CTA or MRA.
* Symptoms onset \< 24h at imaging
* Indication for MT and fulfillment of the following brain imaging criteria :

  1. 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) :
  2. CORE CLINICAL MISMATCH: Core calculated on DWI by RAPID, \<25 mL if NIHSS 6-20 and \<50 mL if NIHSS\>20

     OR (if RAPID results are not considered reliable by the clinician) :
  3. CORE CLINICAL MISMATCH according to the clinician evaluation
* Pre-stroke mRS ≤ 2
* NIHSS ≥ 6

Exclusion Criteria:- Contraindication to MT

* Contraindication to MT
* Patient over 80 years old with \>10 microbleeds on pre-treatment MRI
* Pre-existing dependency with mRS ≥3.
* Known 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)
* Patient benefiting from a legal protection
* Non-membership of a national insurance scheme
* Opposition of the patient or (in case of inclusion as a matter of urgency) of the trustworthy person Participation in another study regarding AIS care interfering with this study

Primary outcomes:
measure: Favorable functional evaluation at 3 month for patients with acute ischemic strocke treated by cangrelor.
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: CHU Lyon
city: Nancy
country: France
facility: CHRU Nancy
city: Paris
country: France
facility: Hôpital Fondation A de Rothschild
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
References: