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Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II (CHANCE-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04078737
Recruitment Status : Active, not recruiting
First Posted : September 6, 2019
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Yongjun Wang, MD, Ministry of Science and Technology of the People´s Republic of China

Tracking Information
First Submitted Date  ICMJE July 8, 2019
First Posted Date  ICMJE September 6, 2019
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE June 29, 2019
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
Any new stroke events (ischemic stroke or hemorrhagic stroke) within 3 months [ Time Frame: 3 months after randomization ]
The aim 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
  • Any new stroke events (ischemic stroke or hemorrhagic stroke) within 1 year [ Time Frame: 1 year after randomization ]
    Percentage of patients with the 1 year new stroke events (ischemic stroke/ hemorrhagic stroke) as a cluster and evaluated individually.
  • 3-month and 1 year new clinical vascular events [ Time Frame: 3 months and 1 yearafter randomization ]
    Percentage of patients with the 3-month and 1 year new events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI(myocardial infarction)/vascular death)
  • 3-month and 1 year new ischemic stroke events [ Time Frame: 3 months and 1 year after randomization ]
    Percentage of patients with the 3-month and 1 year new ischemic stroke will be evaluated.
  • mRS change [ Time Frame: 3 months and 1 year after randomization ]
    Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6 at 3 month/ 1 year follow-up. Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.6 - Dead. The mRS scores between 3 to 6 points are considered to be poor functional outcome. (dead).
  • Further efficacy exploratory analysis: NIHSS change at 3 months [ Time Frame: 3 months after randomization ]
    Further efficacy exploratory analysis: Impairment (changes in NIHSS scores at 3 month follow-up). The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
  • Further efficacy exploratory analysis: Quality of Life [ Time Frame: 3 months and 1 year after randomization ]
    Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale). We will use the EQ-5D-5L scale to evaluate the quality of life. EQ-5D-5L is a standardized instrument for measuring generic health status. It has been widely used in population health surveys, clinical studies, economic evaluation and in routine outcome measurement in the delivery of operational healthcare. The EQ-5D-5L has five domain scales (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression) and five levels for each domain.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 3, 2019)
  • stratified analysis [ Time Frame: 3-month and 1-year after randomization ]
    Efficacy endpoint will also be analyzed stratified by gender (men vs. women), age (<65 vs. ≥65 years), by etiology subtype based on the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype system, by diabetes (yes vs. no) and by type of LOF allele (intermediate metabolizers vs. poor metabolizers), status of intracranial and extracranial artery stenosis (yes vs. no).
  • Moderate and severe bleeding events according to the GUSTO criteria [ Time Frame: 3 months after randomization ]
    Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.
  • Moderate and severe bleeding events according to the GUSTO criteria [ Time Frame: 1 year after randomization ]
    Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage.
  • All bleeding events [ Time Frame: 3 months and 1 year after randomization ]
    All bleeding events (severe/moderate bleeding and intracranial hemorrhage)
  • Total mortality [ Time Frame: 3 months and 1 year after randomization ]
    Total mortality
  • Incidence symptomatic and asymptomatic intracranial hemorrhagic events [ Time Frame: 3 months and 1 year after randomization ]
    Incidence symptomatic and asymptomatic intracranial hemorrhagic events
  • Adverse events [ Time Frame: 3 months and 1 year after randomization ]
    Adverse events
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II
Official Title  ICMJE Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Stroke
  • Transient Ischemic Attack
Intervention  ICMJE
  • Drug: Ticagrelor and Aspirin

    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

  • Drug: Clopidogrel and Aspirin

    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

Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: Ticagrelor and Aspirin
  • Active Comparator: 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
    Intervention: Drug: Clopidogrel and Aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 3, 2019)
6396
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Older than 40 Years ;
  2. Acute onset of cerebral ischemia due to

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

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 ASA (• Known allergy •Severe renal or hepatic insufficiency • Severe cardiac failure, asthma • History of Hemostatic disorder or systemic bleeding • History of thrombocytopenia or neutropenia • History of drug-induced hematologic
  6. Hematokrit(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 (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 bradyarrhythmic 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. Treatment with ticagrelor or clopidogrel 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 or major surgery within 3 months
  22. Diagnosis or suspicious diagnosis of acute coronary syndrome
  23. Participation in another clinical study with an investigational product during the last 30 days.
  24. Currently receiving an investigational drug or device
  25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04078737
Other Study ID Numbers  ICMJE 2017ZX09304018001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yongjun Wang, MD, Ministry of Science and Technology of the People´s Republic of China
Study Sponsor  ICMJE Ministry of Science and Technology of the People´s Republic of China
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yongjun Wang, M.D Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
PRS Account Ministry of Science and Technology of the People´s Republic of China
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP