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

• ClinicalTrials.gov Identifier: NCT04667078
• Recruitment Status: Not yet recruiting
• First Posted: December 14, 2020
• Last Update Posted: February 25, 2022
• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): Fondation Ophtalmologique Adolphe de Rothschild

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemia	Drug: Cangrelor; Other: best medical management	Phase 3

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: experimental group will be treated by P2Y12 inhibitor (cangrelor) in addition to MT and BMM
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: REperfusion With P2Y12 Inhibitors in Addition to mEchanical thRombectomy for perFUsion Imaging Selected Acute Stroke patiEnts (REPERFUSE)
• Estimated Study Start Date: March 15, 2022
• Estimated Primary Completion Date: January 15, 2024
• Estimated Study Completion Date: January 15, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cangrelor group; 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.	Drug: Cangrelor; administration of cangrolor by iv befor thrombectomy
Active Comparator: Best medical management group; 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.	Other: best medical management; used yhe best medical management

Outcome Measures

Primary Outcome Measures :

1. Favorable functional evaluation at 3 month for patients with acute ischemic strocke treated by cangrelor. [ Time Frame: 3 months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18 years or older
• Anterior circulation intracanial large artery occlusion (Intracranial
• Symptoms onset < 24h at imaging
• Indication for thrombectomy and fulfillment of the following brain imaging criteria

Exclusion Criteria:

• Contraindication to TM
• Patient older than 80 years with >10 microbleeds on pre-treatment MRI
• Pre-existing disability: 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)

Contacts and Locations

Contacts

Contact: Mikael Pr Mazighi; 0148036565; mmazighi@for.paris

Contact: Amélie Yavchitz; 0148036565; ayavchitz@for.paris

Sponsors and Collaborators

Fondation Ophtalmologique Adolphe de Rothschild

Ministry of Health, France

Investigators

• Study Chair: Jean-François Dr Albucher; CHU Toulouse
• Study Chair: Gauthier Dr Marnat; CHU Bordeaux
• Study Chair: Benjamin Dr Gory; CHRU Nancy
• Study Chair: Tae-Hee Dr Cho; CHU LYON
• Study Chair: Lucie Dr Della Schiava; CHRU Lille
• Study Chair: Aymeric Dr Rouchaud; CHU Limoges
• Study Chair: Benjamin Pr Lapergue; Hôpital Foch

More Information

• Responsible Party: Fondation Ophtalmologique Adolphe de Rothschild
• ClinicalTrials.gov Identifier: NCT04667078
• Other Study ID Numbers: MMI_2020_35
• First Posted: December 14, 2020
• Last Update Posted: February 25, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Stroke; Ischemia; Pathologic Processes; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cangrelor; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs