Efficacy Study of Clopidogrel in High-risk Population With Acute Non-disabling Cerebrovascular Events Ⅱ

Transient Ischemic Attack Clinical Trial

Official title:

Multicentre, Double-blind, Double-simulation, Randomized Controlled Clinical Trial of Ticagrelor/Aspirin Versus Clopidogrel/Aspirin for the Prevention of Stroke in a Population at High Risk for Non-crippling Cerebrovascular Events Carrying the CYP2C19 LOF Allele

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04952311
• Other study ID #: M2020521
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2019
• Est. completion date: September 30, 2021

Study information

• Verified date: June 2021
• Source: Peking University Third Hospital
• Contact: Yu Fu
• Phone: +86 15611908699
• Email: lilac_fu[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to test whether ticagrelor combined with aspirin can reduce the recurrence rate of stroke within 3 months compared with clopidogrel combined with aspirin in patients at high risk of non-disablement ischemic cerebrovascular events who carry the CYP2C19 function loss allele within 24 hours of onset.

Description:

This study was a multicenter, double-blind, double-simulated, randomized controlled study. To test whether ticagrelor combined with aspirin reduces the recurrence rate of stroke within 3 months compared with clopidogrel combined with aspirin in patients with a high risk of noncrippling ischemic cerebrovascular events with CYP2C19 loss within 24 hours of onset.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10878
• Est. completion date: September 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Age =40;

2. Patients with acute non-disabling ischemic stroke or transient ischemic attack (TIA) who meet the following definitions:

• Acute non-disabling ischemic stroke: NIHSS score =3 at enrolment,

• Mediate-high risk of stroke TIA: ABCD2 score =4;

3. Study drugs can be administered within 24 hours of symptoms * appearing;

4. CYP2C19 loss allele carriers;

5. Signed informed consent.

Exclusion Criteria:

1. Hemorrhage or other pathological brain disease, such as vascular malformation, tumor, abscess, or other common non-ischemic brain disease (e.g., multiple sclerosis), as diagnosed by CT or MRI of the head at baseline.

2. There were only isolated sensory symptoms (e.g., numbness), isolated visual changes, isolated dizziness or vertigo, but no evidence of acute infarction on baseline head CT or MRI.

3. Mild stroke /TIA due to angioplasty/vascular surgery. 4. Pre-onset MRS score > Two points. Pre-onset MRS score [Note: According to the patient's pre-onset history assessment, if patients with MRS> score of 2 were not included] 5. There are contraindications for the use of clopidogrel, ticagrelor or aspirin.

• a known history of allergies;

• Severe liver or renal insufficiency;

• (Severe liver dysfunction is defined as ALT value > 2 times the upper normal limit or AST value > 2 times the upper normal limit; Severe renal insufficiency was defined as creatinine > 1.5 times the upper normal limit);

• Severe heart failure (NYHA rating ? and AA);

• A history of coagulation disorders or systemic bleeding;

• A history of thrombocytopenia or neutropenia;

• A history of blood-system disease or abnormal liver function caused by drugs;

• Leukopenia (lt; 2×109/L) or thrombocytopenia (< 100 x 109 / L); Hematocrit < 30%. 7. There are clear indications of anticoagulant therapy (suspected cardiac embolism, such as atrial fibrillation, known artificial heart valves, suspected endocarditis, etc.).

8. Have a history of intracranial hemorrhage or a history of amyloid cerebrovascular disease.

9. A history of aneurysms (including intracranial and peripheral aneurysms). A history of asthma or COPD (chronic obstructive pulmonary disease). 11. High risk bradyarrhythmias, such as disordered sinus syndrome, second or third degree atrioventricular block, bradycardia associated syncope due to absence of a pacemaker.

12. A history of hyperuric acid nephropathy (fasting serum uric acid content in men and menopausal women on two different days under the condition of anopurine diet > 420umol/L(7.0mg/ dL), premenopausal women > 357 umol/L (6.0 mg/dl).) .

13. It is expected that it will be possible for a long time (gt; 7 days) take any non-steroidal anti-inflammatory drugs other than aspirin.

14. Surgical or endovascular treatment is expected to be required in the next 3 months.

15. Discontinuation of the experimental drug may be required for other planned surgical or interventional therapies.

16. Severe non-cardio-cerebrovascular diseases with an expected survival time of less than 3 months.

17. Inability to understand and/or comply with study procedures and/or follow-up due to mental illness, cognitive or emotional disorder.

18. Two or more antiplatelet drugs were taken within 72 hours before enrolment. 19. Heparin or oral anticoagulants were used within 10 days before enrollment. 20. Patients who had received intravenous or arterial thrombolysis or mechanical thrombectomy within 24 hours before enrollment.

21. A history of gastrointestinal bleeding within 3 months before enrollment or major surgery within 30 days.

22. Confirmed or suspected acute coronary syndrome. 23. Participated in other clinical drug studies in the past 30 days. 24. Experimental drug or instrument tests are under way. 25. Women of childbearing age, pregnancy or breastfeeding who have negative pregnancy tests but refuse to use effective contraceptives.

Related Conditions & MeSH terms

• Ischemia
• Ischemic Attack, Transient
• Transient Ischemic Attack

Intervention

Drug:
• Tagrelor combined with aspirin
Combination of ticagrelor (first 180mg a day, 90mg/ d, 2 times/d) with aspirin (first 75 to 300mg/ d, 75mg/ d, 2 days/d) for 21 days followed by ticagrelor (90mg/ d, 2 times/d) alone for 3 months
• Clopidogrel combined with aspirin
Clopidogrel (first dose 300mg daily, 75mg/ d from day 2) was combined with aspirin (first dose 75-300mg/ d, 75mg/ d from day 2) for 21 days, followed by clopidogrel (75mg/ d) alone for up to 3 months

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University Third Hospital	Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	new stroke event	Any new stroke event (ischemic stroke or hemorrhagic stroke) within 3 months	3 months
Secondary	new stroke event	Any new stroke event (ischemic stroke or hemorrhagic stroke) within 1 year	1 year