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NCT04078737

Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II

Last Updated: 2021-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

6412 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-23

Study Completion Date

2021-07-01

Brief Summary

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The primary objective of this trial is to assess the effects of ticagrelor plus aspirin versus clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.

Detailed Description

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According to the Global Burden of Disease(GBD) Study 2016, China bears the greatest lifetime risk of stroke from 25-year-age onward. Minor ischemic events, including minor stroke and TIA, were major parts of stroke manifestations. Events (CHANCE) has shown that 21-day dual antiplatelet therapy (clopidogrel and aspirin) compared to aspirin alone which initiated within 24 hours after symptoms onset would reduce 32% risk of stroke recurrence within 90 day, but not in carriers of CYP2C19 loss-of-function (LOF) alleles. The primary purpose of this study is to compare ticagrelor plus aspirin with clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.

Both intent analysis (ITT) and compliance program set (PPS) were used for analysis.

We will use Kaplan-Meier estimates of the cumulative risk of stroke (ischemic or hemorrhagic) event during maximum 90-day follow-up, with hazards ratios and 95% CI calculated using Cox proportional hazards methods and the log-rank test to evaluate the treatment effect. All statistics will be 2-sided with P\<0.05 considered significant, accounting for interim analyses.

All patients who received study drugs and with at least one safety follow-up record will be included in the safety population. The data for safety evaluation included adverse reactions observed during the trial and changes in laboratory data before and after treatment.

Conditions

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Stroke Transient Ischemic Attack

Keywords

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stroke transient ischemic attack acute treatment acute non-disabling cerebrovascular event clopidogrel ticagrelor clopidogrel combined with ASA ticagrelor combined with ASA recurrence of stroke and other vascular events CYP2C19 loss-of-function allele(s) carrier

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Study Groups

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Ticagrelor plus Aspirin Group

Ticagrelor of loading dosing of 180mg followed by 90mg bid for 3 months plus aspirin of loading dose of 75-300mg followed by 75mg daily for 21 days

Group Type EXPERIMENTAL

Ticagrelor and Aspirin

Intervention Type DRUG

Day of randomization:

Day1:Ticagrelor 180mg; placebo of clopidogrel 300mg; aspirin 75-300mg (open label) Day2-21st: Ticagrelor 90mg bid/day; placebo of clopidogrel 75mg; aspirin 75mg (open label) Day 22nd-3 months:Ticagrelor 90mg bid/day; placebo of clopidogrel 75mg

Clopidogrel plus Aspirin Group

Clopidogrel of loading dosing of 300mg followed by 75mg daily for 3 months plus aspirin loading dose of 75-300mg followed by 75mg daily for 21 days

Group Type ACTIVE_COMPARATOR

Clopidogrel and Aspirin

Intervention Type DRUG

Day of randomization:

Day 1: Clopidogrel 300mg; placebo of ticagrelor 180mg; aspirin 75-300mg (open label) Day2-21st: Clopidogrel 75mg/day; placebo of ticagrelor 90mg bid/day; aspirin 75mg (open label) Day 22nd-3 months:Clopidogrel 75mg; placebo of ticagrelor 90mg bid/day

Interventions

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Ticagrelor and Aspirin

Intervention Type DRUG

Clopidogrel and Aspirin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 40 years or older than 40 years；
2. Acute cerebral ischemic event due to：

* Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization)or，
* TIA with moderate-to-high risk of stroke (ABCD2 score ≥ 4 at the time of randomization)；
3. Can be treated with study drug within 24 hours of symptoms onset\*(\*Symptom onset is defined by the "last seen normal" principle)；
4. CYP2C19 loss-of-function allele carriers；
5. Informed consent signed.

Exclusion Criteria

1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.
2. Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI.
3. Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA.
4. Preceding moderate or severe dependency (modified Rankin scale \[mRS\] score 3-5).
5. Contraindication to clopidogrel, ticagrelor or aspirin

* Known allergy
* Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range) or hepatic (ALT or AST \> twice the upper limit of normal range) insufficiency
* Severe cardiac failure (NYHA level: III to IV)
* History of hemostatic disorder or systemic bleeding
* History of thrombocytopenia or neutropenia
* History of drug-induced hematologic disorder or hepatic dysfunction
* Low white blood cell (\<2×109/L) or platelet count (\<100×109/L)
6. Hematocrit (HCT) \<30%
7. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)
8. History of intracranial hemorrhage or amyloid angiopathy
9. History of aneurysm (including intracranial aneurysm and peripheral aneurysm)
10. History of asthma or COPD (chronic obstructive pulmonary disease)
11. High-risk for bradyarrhythmia (first-degree or second-degree AV block caused by sinus node disease, and brady-arrhythmic syncope without pacemaker)
12. History of hyperuricemia nephropathy
13. Anticipated requirement for long-term (\>7 days) non-steroidal anti-inflammatory drugs (NSAIDs)
14. Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
15. Scheduled for surgery or interventional treatment requiring study drug cessation
16. Severe non-cardiovascular comorbidity with life expectancy \< 3 months
17. Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders
18. Dual antiplatelet treatment (or more than two antiplatelet agents) in 72 hours before randomization
19. Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation
20. Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy within 24 hours prior to randomization
21. Gastrointestinal bleed within 3 months or major surgery within 30 days
22. Diagnosis or suspicious diagnosis of acute coronary syndrome
23. Participation in another clinical study with an experimental product during the last 30 days
24. Currently receiving an experimental drug or device
25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control

Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Yongjun Wang

President of Beijing Tiantan Hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yongjun Wang, M.D

Role: PRINCIPAL_INVESTIGATOR

Beijing Tian Tan Hospital, Capital Medical University, Beijing, China

Locations

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Anqing Municipal Hospital

Anqing, Anhui, China

Site Status

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Site Status

Beijing Chaoyang Hospital, Capital MedicalUniversity（west Hospital）

Beijing, Beijing Municipality, China

Site Status

Beijing Tian tan Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Shunyi Airport Hospital

Beijing, Beijing Municipality, China

Site Status

The First Hospital of Fangshan District

Beijing, Beijing Municipality, China

Site Status

Beijing Coal Group Hospital

Beijing, Beijing Municipality, China

Site Status