ACUTE-PRAS

JRCT ID: jRCTs031220079

Registered date:20/05/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Acute-phase Atherothrombotic Cerebral Infarction and high risk TIA
• Date of first enrollment: 04/07/2022
• Target sample size: 200
• Study type: Interventional

Intervention(s)

Prasugrel group
Plasugrel and aspirin are administered once daily by Oral.
The basic duration of dual antiplatelet therapy is 21 days according to the stroke treatment guidelines 2021.

Standard group
Clopidogrel and aspirin are administered once daily by Oral.
The dose of clopidogrel is set at the discretion of the investigator for each patients according to the Japanese and overseas guidelines.
The basic duration of dual antiplatelet therapy is 21 days according to the stroke treatment guidelines 2021.

Outcome(s)

Primary Outcome

EFFICACY ASSESSMENTS
-Platelet aggregation (PRU) at 5 days after administration of the study drug in patients with each genetic polymorphism of CYP2C19
-Platelet aggregation (PRU) at 5 days after administration of the study drug in all patients

Secondary Outcome

EFFICACY ASSESSMENTS
-Proportion of PRU/Asprin Reaction Unit and high platelete reactivity (PRU > 208) by CYP2C19 genetic polymorphism in all patients, Extensive Metabolizer, Intermediate Metabolizer, and Poor Metabolizer (predose, at 12 hours to 48 hours postdose, and at 5 days postdose)
-Presence or absence of a new infarction evaluated by MRI diffusion-weighted imaging (before administration, at 5 days after administration)
-Cumulative Incidence of the following Cerebro and Cardiovascular Events
1.Stroke (cerebral infarction, cerebral hemorrhage, and Subarachnoid hemorrhage) and TIA
2.myocardial infarction
3.death (all-cause death, vascular death, ischemic vascular death, other reasons)
4.composite endpoint 1 (cerebral infarction, myocardial infarction, ischemic vascular death)
5.composite endpoint 2 (composite endpoint 1, and TIAs)
6.Other event of arterial thrombosis and embolism
-NIHSS score (before administration, at 5 days after administration, at 21 days after administration, or at discharge, whichever comes first)
-Modified Rankin Scale (at 21 days after administration or at discharge, whichever comes first, and 90 days after administration)

Safety endpoints
-Cumulative Incidence of the following Bleeding Events
1.Major bleeding (POINT study criteria)
2.Minor bleeding (POINT study criteria)
3.Intracranial hemorrhage (Symptomatic intracranial hemorrhage, asymptomatic intracranial hemorrhage)
4.Other bleeding events (ISTH bleeding criteria: major bleeding, GUSTO bleeding criteria: Severe or life-threatening bleeding, moderate bleeding, minor bleeding, MATCH bleeding criteria: life-threatening bleeding, major bleeding, clinically significant bleeding, and other bleeding)
-Other Adverse Event Items

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Patients age are over 20 years at informed consent
2.Patients with acute atherothrombotic cerebral infarction (with a stenosis rate of >= 50% in diameter or complete occlusion of the culprit vessel due to atherosclerosis) with a NIH Stroke Scale score of <= 10 or patients with high-risk TIA (ABCD2 risk score >= 4 or paralyzed)
3.Patients who can receive the study drug within 48 hours after onset of symptoms. The origin of symptom onset is defined as the time point when the normal condition was finally confirmed
4.Patients with at least one of the following risk factors
i)Hypertension: patients with a systolic blood pressure of 140 mmHg and a diastolic blood pressure of 90 mmHg or higher, or patients who received therapeutic drugs
ii)Diabetes mellitus: HbA1c >= 6.5% or patients who received therapeutic drugs
iii)Chronic kidney disease: patients with eGFR < 60 mL/min/1.73 m2 or urinary protein >= 1+
iv)Dyslipidemia: LDL cholesterol >= 120 mg/dL, HDL cholesterol < 40 mg/dL, triglyceride >= 150 mg/dL, or therapeutic drugs
v)Medical history of cerebral infarction before the onset of index cerebral infarction or TIA
5.Patients from whom written informed consent is obtained after receiving an explanation on the details of this clinical study (consent obtained from patients as long as possible after consent from their legally acceptable representative in urgent situations)

Exclude criteria

1.Patients with a baseline modified Rankin Scale of >= 3
2.Patients who cannot undergo a brain MRI
3.Patients with moderate or high-risk cardiogenic embolic sources in the TOAST classification
4.Patients with or have a medical history of symptomatic nontraumatic intracranial hemorrhage, excludes asymptomatic microbleeding found only on MRI
5.Patients with subarachnoid hemorrhage or with high risk of subarachnoid hemorrhage such as an untreated unruptured cerebral aneurysm of 5 mm or more
6.Patients with cerebral hemorrhage at enrollment which are hemorrhagic infarction, vitreous bleeding, retinal bleeding, blood stasis, hematemesis, bloody urine, bloody stool, melena, hemorrhage, etc., and patients with a high risk of cerebral hemorrhage which are congenital or acquired bleeding diseases, blood coagulation disorders, platelet abnormalities, peptic ulcer etc.
7.Patients who were planned to undergo endovascular thrombectomy or cerebral revascularization, which are carotid endarterectomy, carotid artery stenting etc., for the last cerebral ischemic attack at enrollment
8.Patients who have undergone or were planned to undergo Intravenous rt-PA therapy etc., for the index cerebral infarction at enrollment
9.Patients who scheduled for surgery requiring discontinuation of the study drug during clinical trial
10.Patients who have severe hepatic disorder (fulminant hepatitis, cirrhosis, malignant liver tumors etc.,)
11.Patients who have severe renal disorder requiring dialysis
12.Patients with malignant tumors with requirement for treatment
13.Autoimmune disease
14.Patients who received antiplatelet drugs except for aspirin (such as clopidogrel, prasugrel, cilostazol, ticlopidine or ozagrel sodium) and Anticoagulant (excluding argatroban) within 14 days prior to the initiation of the study treatment
15.Patients who have a medical history of significant side effects or contraindications to prasugrel, clopidogrel or aspirin and patients with a medical history of serious drug allergy (including hypersensitivity to ingredients of this drug)
16.Patients who were pregnant, breastfeeding, or possibly pregnant or planned to be pregnant
17.Patients who are planning to participate in or are participating in other clinical trials during this clinical trial
18.Patients who were judged by the investigator to be ineligible for the study

Related Information

• Primary Sponsor: Fujimoto Shigeru
• Source(s) of Monetary Support: Daiichisankyo CO.,LTD