StrokePhase 2/3PRINCENCT02506140
Platelet Reactivity in Acute Non-disabling Cerebrovascular Events
A Phase 2/3 study testing Ticagrelor and Acetylsalicylic acid and Clopidogrel and Acetylsalicylic acid in people with Stroke and Ischemic Attack, Transient, run by Beijing Tiantan Hospital at 25 sites in China.
Trial summary
Ticagrelor is a reversible and direct-acting oral antagonist of the P2Y12 (Purinergic receptor P2Y, G-protein coupled, 12) receptor for adenosine diphosphate, which provides faster, greater, and more consistent P2Y12 inhibition than Clopidogrel in patients with acute coronary syndrome, irrespective of the genetic… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Stroke, Ischemic Attack, Transient
- What is being tested?
- Ticagrelor and Acetylsalicylic acid and Clopidogrel and Acetylsalicylic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 675 participants
- Where
- 25 sitesChina
- Study dates
- Aug 2015to Mar 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent.
- Female or male aged≥ 40 years and <80 years.
- Acute non-disabling ischemic stroke (NIHSS≤ 3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset defined by the"last see normal"principle.
- TIA (Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with study drug within 24 hours of symptoms onset and with moderate-to-high risk of stroke recurrence (ABCD2 score ≥ 4 at the time of randomization or the stenosis of offending vessel ≥ 50%).
Who cannot join
- Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head Computed Tomography (CT) or magnetic resonance imaging (MRI).
- 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.
- Modified Rankin Scale Score > 2 at randomization (pre-morbid historical assessment)。
- Contraindication to ticagrelor, clopidogrel or acetylsalicylic acid :
- Known hypersensitivity
- Severe renal or hepatic insufficiency
Show all 32Show fewer
- Severe cardiac failure, asthma
- Hemostatic disorder or systemic bleeding
- History of hemostatic disorder or systemic bleeding
- History of drug-induced hematologic or hepatic abnormalities
- Low white blood cell (<2 x10^9/L) or platelet count (<100 x10^9/L)
- Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, ventricular aneurysm, prosthetic cardiac valves known, suspected endocarditis or other suspicion of cardioembolic pathology for TIA/stroke).
- Continuous use of ticagrelor or clopidogrel over 5 days before randomization
- Current treatment (last dose given within 10 days before randomization) with heparin therapy or anti coagulation therapy (e.g., warfarin; thrombin inhibitors such as dabigatran , argatroban, bivalirudin, ximelagatran; factor Xa inhibitors such as rivaroxaban, edoxaban, apixaban, betrixaban, tanexaban ; hirudin; unfractionated and low molecular weight heparins ).
- Receipt of intravenous/ intra-arterial thrombolysis or mechanical thrombectomy within 24 hours prior to randomization.
- History of intracranial hemorrhage or cerebral artery amyloidosis.
- History of aneurysm (including intracranial aneurysm or peripheral aneurysms)
- Diagnosis or of acute coronary syndrome.
- History of asthma or COPD (chronic obstructive pulmonary disease).
- High risk of bradyarrhythmia, such as sick sinus syndrome second-degree or third-degree atrioventricular block, bradycardia-related syncope without installed pacemaker.
- History of uric acid nephropathy.
- Anticipated requirement for long-term (>7 days) non-study anti-platelet drugs, or NSAIDs (nonsteroidal antiinflammatory drugs) affecting platelet function.
- History of previous symptomatic non-traumatic intracerebral bleed at any time (asymptomatic microbleeds do not qualify), gastrointestinal (GI) bleed within the past 3 months, or major surgery within 30 days.
- Qualifying TIA or minor stroke induced by angiography or surgery.
- Planned or likely revascularization within the next 3 months.
- Scheduled for surgery or interventional treatment requiring study drug cessation.
- Severe non-cardiovascular comorbidity with life expectancy < 3 months.
- Pregnancy or lactation, and women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test.
- Currently receiving an investigational drug or device.
- Participation in another clinical study with an investigational product during the last 30 days.
- Inability of the patient to understand and/or comply with study procedures and/or follow-up, in the opinion of the Investigator.
- Hematocrit (Hct) < 30%
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
China25 sites
Aviation General Hospital of China Medical University
Beijing, 100012
Beijing Tian Tan Hospital, Capital Medical University
Beijing, 100050
Dongfang Hospital Beijing University of Chinese Medicine
Beijing, 100078
The First Hospital of Fangshan District,Beijing
Beijing, 102400
Xiangya Hospital Central South University
Changsha, Hunan, 410008
Daping Hospital,Third Military Medical University
Chongqing, 400042
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005
Renji Hospital,Shanghai Jiao Tong University School of Medicine
Shanghai, 200127
General Hospital of Shenyang Military
Shengyang, Liaoning, 110016
The Second People's Hospital of Shenzhen
Shenzhen, Guangdong, 518000
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050000
The Second Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030001
General Hospital of TISCO
Taiyuan, Shanxi, 030003
Taizhou First People's Hospital,Huangyan Hospital of Wenzhou Medical University
Taizhou, Zhejiang, 318020
North China University of Science And Technology Affiliated Hospital
Tangshan, Hebei, 063000
Tangshan Gongren Hospital
Tangshan, Hebei, 063000
Tianjin Huanhu Hospital
Tianjin, 300350
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Wenzhou Hospital of integrated Chinese and Western medicine
Wenzhou, Zhejiang, 325000
Wuhan Brain Hospital,General Hospital of The Yangtze River Shipping
Wuhan, Hubei, 430014
Union Hospital,Tongji Medical College,Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Wuhan No.1 Hospital
Wuhan, Hubei, 430022
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060
Northern Jiangsu People's Hospital,Clinical Medical School,YangZhou University
Yangzhou, Jiangsu, 225001
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052
About this study
Official title: A Randomized, Open-label, Active-Controlled and Blinded-Endpoint Trial Comparing the Antiplatelet Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin in Chinese Patients With High-risk Transient Ischemic Attack or Minor Stroke.
Ticagrelor is a reversible and direct-acting oral antagonist of the P2Y12 (Purinergic receptor P2Y, G-protein coupled, 12) receptor for adenosine diphosphate, which provides faster, greater, and more consistent P2Y12 inhibition than Clopidogrel in patients with acute coronary syndrome, irrespective of the genetic variants affecting Clopidogrel metabolism. It is still undefined whether combination therapy of Ticagrelor and Aspirin is more effective than Clopidogrel and aspirin for minor stroke and transient ischemic attack (TIA). The primary purpose of the PRINCE trial is to evaluate the anti-platelet effects of a 3-month regimen of ticagrelor initiated with 180 mg loading dose followed by 90 mg twice/day combined with aspirin 100 mg/day during first 21 days versus a 3-month regimen of clopidogrel initiated with 300 mg loading dose of followed by 75 mg/day combined with aspirin 100 mg/day during first 21 days when initiated within 24 hours of symptom onset in high-risk transient ischemic attack or minor stroke.
Read the detailed description
The PRINCE trial is a prospective, randomized, multi-centre, open-label, active-controlled, blinded-endpoint trial (a PROBE design concerning clinical trial). A total of approximately 952 patients (40years≤Age<80years) with high-risk TIA (defined as an ABCD2 score ≥ 4 or the stenosis of offending vessel ≥ 50%) or minor ischemic stroke (defined as an NIHSS ≤ 3), who can be treated within 24 hours of symptom onset will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups after offering informed content: 1) one group will receive a 180 mg loading dose of ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to 3 months; 2) the other group will receive a 300 mg loading dose of clopidogrel on the day of randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months. Aspirin will be given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21 in the both groups. The primary objective is to assess the anti-platelet effects of Ticagrelor combined with Aspirin versus Clopidogrel combined with Aspirin in Chinese patients with high-risk TIA and minor stroke. The study consists of six visits including the day of randomization, 2 hours after the first anti-platelet agents, 24 hours after the first anti-platelet agents, Day 7+2days, Day 21±2days and Day 90±7days. Genomic DNA of all patients will be collected for genotyped. And the genetic variants affecting Clopidogrel metabolism will be analyzed. The antiplatelet effects will be analyzed in total subjects and genetic variants carriers. The trial is anticipated to complete in 18 months from the first subject recruitment , with 952 subjects recruited from 25 centres in China. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by IRB(Institutional Review Board) /EC(Ethics Committee) in Beijing Tiantan hospital, Capital Medical University.
- Conditions
- Stroke, Ischemic Attack, Transient
- Being tested
- Ticagrelor and Acetylsalicylic acid, Clopidogrel and Acetylsalicylic acid
- Keywords
- minor stroke, transient ischemic attack, ticagrelor, clopidogrel, dual anti-platelet therapy, platelet reactivity
- Medical subject headings
- Stroke, Ischemic Attack, Transient
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor and Acetylsalicylic acidDrug
Also called BRILINTA, Aspirin
This group will receive a 180 mg loading dose of ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21.
Clopidogrel and Acetylsalicylic acidDrug
Also called Plavix, Aspirin
This group will receive a 300 mg loading dose of clopidogrel on the day of randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21.
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor/ASA | Experimental | Drugs: Ticagrelor and Acetylsalicylic acid. Receives: Drug: Ticagrelor and Acetylsalicylic acid |
| Clopidogrel/ASA | Active comparator | Drugs: Clopidogrel and Acetylsalicylic acid. Receives: Drug: Clopidogrel and Acetylsalicylic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
High on-treatment platelet reactivity (HOPR) defined as P2Y12 reaction unit (PRU)> 208 measured by VerifyNow® assay at 90 days
Measured: 90 days
Secondary outcomes (24)
HOPR at 90 days in subjects carrying genetic variants which affected Clopidogrel metabolism.
HOPR defined as P2Y12 reaction unit (PRU)> 208 measured by VerifyNow® assay
Measured: 90 days
New vascular events defined as any event of the following: Any stroke (ischemic or hemorrhage).
All the new vascular events will be assessed by at least two neurologists based on neuroimaging and clinical feature. When there was disagreement, a third senior neurologist was consulted to reach a consensus decision.
Measured: 90 days, 6 months, 1 year
New composite clinical vascular events (ischemic stroke/ hemorrhagic stroke/TIA/ myocardial infarction/ vascular death) as a cluster.
All the new composite clinical vascular events will be assessed by at least two neurologists based on laboratory examination, imaging and clinical feature. When there was disagreement, a third senior neurologist was consulted to reach a consensus decision.
Measured: 90 days, 6 months, 1 year
High on-treatment platelet reactivity defined as PRU> 208 measured by VerifyNow® assay.
Measured: 2hours, 24 hours, 7 days
High on-treatment platelet reactivity defined as Aspirin reactivity unit (ARU)> 555 measured by VerifyNow® assay.
Measured: 7 days
HOPR defined as Maximum Amplitude-adenosine diphosphate (MA-ADP)>47 measured by Thrombelastography Platelet Mapping Assay (TEG) using the inducer of adenosine diphosphate.
Measured: 90 days
Residual platelet reactivity defined as the value of PRU.
Measured: 2hours, 24 hours, 7 days, 90 days
Residual platelet reactivity defined as the value of Aspirin reaction unit (ARU).
Measured: 7days
Residual platelet reactivity defined as the value of MA-ADP.
Measured: 7days, 90 days
Residual platelet reactivity defined as the value of Maximum Amplitude- acetylsalicylic acid (MA-AA) measured by TEG.
Measured: 7days
Residual platelet reactivity change from baseline in PRU.
Measured: 2hours, 24 hours, 7 days, 90 days
Residual platelet reactivity change from baseline in ARU.
Measured: 7 days
The inhibition of platelet aggregation (IPA) measured by VerifyNow® assay.
Measured: 2hours, 24 hours, 7 days, 90 days
The TEG-platelet inhibition(TPI)measured by TEG.
Measured: 7 days, 90 days
Platelet inhibition change from baseline in IPA.
Measured: 2hours, 24 hours, 7 days, 90 days
Platelet inhibition change from baseline in TPI.
Measured: 7 days, 90 days
Residual platelet reactivity detected by AspirinWorks.
Measured: 7days
Residual platelet reactivity detected by PL Platelet Analyser (SINNOWA®).
Measured: 7days, 90days
Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6.
Measured: 90 days, 6 months, 1 year
Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 90 days, 6 months, 1 year follow-up)
Measured: 90 days, 6 months, 1 year
Further efficacy exploratory analysis:Quality of Life (The EuroQol-5D 3 level version[EQ-5D-3L]scale).
Measured: 90 days, 6 months, 1 year
Major bleed (PLATO definition), including fatal/life-threatening and other.
The PLATO(Platelet Inhibition and Patient Outcomes) definition of fatal/life-threatening of major bleed is any one of the following: Fatal, Intracranial, Intrapericardial bleed with cardiac tamponade, Hypovolaemic shock or severe hypotension due to bleeding and requiring pressors or surgery, Clinically overt or apparent bleeding associated with a decrease in hemoglobin(Hb) of more than50 g/L, Transfusion of 4 or more units (whole blood or packed red blood cells [PRBCs]) for bleeding. The PLATO definition of other of major bleed is any one of the following:Significantly disabling (eg. intraocular with permanent vision loss), Clinically overt or apparent bleeding associated with a decrease in Hb of 30 g/L to 50 g/L, Transfusion of 2-3 units (whole blood or PRBCs) for bleeding.
Measured: 90 days, 6 months, 1 year
Intracranial hemorrhagic events.
Intracranial hemorrhagic events is assessed by brain computed tomography (CT) or gradient recalled echo (GRE) T2 star weighted MRI.
Measured: 90 days, 6 months, 1 year
Total mortality.
All deaths reported post-randomization will be recorded and adjudicated. Deaths will be subclassified by the adjudication committee as cardiovascular or non-cardiovascular.
Measured: 90 days, 6 months, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2015 (estimated)
- Study startAug 2015
- Primary completionMar 2017
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 675 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Municipal Science & Technology Commission
- Responsible party
- Principal investigator, Yongjun Wang, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02506140
- Sponsor's protocol ID
- D151100002015001
- Other IDs
- 81322019
- Acronym
- PRINCE
- Status last verified
- Dec 2017
- First submitted
- 19 Jul 2015
- Last updated
- 24 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yang Y, Chen W, Pan Y, Yan H, Meng X, Liu L, Wang Y, Wang Y. Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA. Front Neurol. 2020 Jun 10;11:534. doi: 10.3389/fneur.2020.00534. eCollection 2020.
PubMed 32587571Yang Y, Chen W, Meng X, Liu L, Wang Y, Pan Y, Wang Y. Impact of smoking on platelet function of ticagrelor versus clopidogrel in minor stroke or transient ischaemic attack. Eur J Neurol. 2020 May;27(5):833-840. doi: 10.1111/ene.14171. Epub 2020 Mar 8.
PubMed 32052517Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y; PRINCE Protocol Steering Group. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. BMJ. 2019 Jun 6;365:l2211. doi: 10.1136/bmj.l2211.
PubMed 31171523Wang Y, Lin Y, Meng X, Chen W, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Liu L, Zhao X, Wang Y; PRINCE Protocol Steering Group. Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design. Int J Stroke. 2017 Apr;12(3):321-325. doi: 10.1177/1747493017694390. Epub 2017 Jan 1.
PubMed 28381198
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Active-Controlled and Blinded-Endpoint Trial Comparing the Antiplatelet Effects of Ticagrelor Plus Aspirin Versus Clopidogrel Plus Aspirin in Chinese Patients With High-risk Transient Ischemic Attack or Minor Stroke.
- ClinicalTrials.gov ID
- NCT02506140
- Acronym / sponsor ID
- PRINCE / D151100002015001
- Conditions
- Stroke, Ischemic Attack, Transient
- Keywords
- minor stroke, transient ischemic attack, ticagrelor, clopidogrel, dual anti-platelet therapy, platelet reactivity
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 675 participants (actual)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- Beijing Municipal Science & Technology Commission
- Study start
- Aug 2015
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 23 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ticagrelor is a reversible and direct-acting oral antagonist of the P2Y12 (Purinergic receptor P2Y, G-protein coupled, 12) receptor for adenosine diphosphate, which provides faster, greater, and more consistent P2Y12 inhibition than Clopidogrel in patients with acute coronary syndrome, irrespective of the genetic variants affecting Clopidogrel metabolism. It is still undefined whether combination therapy of Ticagrelor and Aspirin is more effective than Clopidogrel and aspirin for minor stroke and transient ischemic attack (TIA). The primary purpose of the PRINCE trial is to evaluate the anti-platelet effects of a 3-month regimen of ticagrelor initiated with 180 mg loading dose followed by 90 mg twice/day combined with aspirin 100 mg/day during first 21 days versus a 3-month regimen of clopidogrel initiated with 300 mg loading dose of followed by 75 mg/day combined with aspirin 100 mg/day during first 21 days when initiated within 24 hours of symptom onset in high-risk transient ischemic attack or minor stroke.
Detailed description
The PRINCE trial is a prospective, randomized, multi-centre, open-label, active-controlled, blinded-endpoint trial (a PROBE design concerning clinical trial). A total of approximately 952 patients (40years≤Age<80years) with high-risk TIA (defined as an ABCD2 score ≥ 4 or the stenosis of offending vessel ≥ 50%) or minor ischemic stroke (defined as an NIHSS ≤ 3), who can be treated within 24 hours of symptom onset will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups after offering informed content: 1) one group will receive a 180 mg loading dose of ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to 3 months; 2) the other group will receive a 300 mg loading dose of clopidogrel on the day of randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months. Aspirin will be given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21 in the both groups. The primary objective is to assess the anti-platelet effects of Ticagrelor combined with Aspirin versus Clopidogrel combined with Aspirin in Chinese patients with high-risk TIA and minor stroke. The study consists of six visits including the day of randomization, 2 hours after the first anti-platelet agents, 24 hours after the first anti-platelet agents, Day 7+2days, Day 21±2days and Day 90±7days. Genomic DNA of all patients will be collected for genotyped. And the genetic variants affecting Clopidogrel metabolism will be analyzed. The antiplatelet effects will be analyzed in total subjects and genetic variants carriers. The trial is anticipated to complete in 18 months from the first subject recruitment , with 952 subjects recruited from 25 centres in China. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been approved by IRB(Institutional Review Board) /EC(Ethics Committee) in Beijing Tiantan hospital, Capital Medical University.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor/ASA | Experimental | Drug: Ticagrelor and Acetylsalicylic acidDrugs: Ticagrelor and Acetylsalicylic acid. |
| Clopidogrel/ASA | Active comparator | Drug: Clopidogrel and Acetylsalicylic acidDrugs: Clopidogrel and Acetylsalicylic acid. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of informed consent.
- Female or male aged≥ 40 years and <80 years.
- Acute non-disabling ischemic stroke (NIHSS≤ 3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset defined by the"last see normal"principle.
- TIA (Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with study drug within 24 hours of symptoms onset and with moderate-to-high risk of stroke recurrence (ABCD2 score ≥ 4 at the time of randomization or the stenosis of offending vessel ≥ 50%).
Key exclusion criteria (32 listed)
- Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head Computed Tomography (CT) or magnetic resonance imaging (MRI).
- 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.
- Modified Rankin Scale Score > 2 at randomization (pre-morbid historical assessment)。
- Contraindication to ticagrelor, clopidogrel or acetylsalicylic acid :
- Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, ventricular aneurysm, prosthetic cardiac valves known, suspected endocarditis or other suspicion of cardioembolic pathology for TIA/stroke).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ticagrelor and Acetylsalicylic acidAlso: BRILINTA, AspirinThis group will receive a 180 mg loading dose of ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21. | Drug | Ticagrelor/ASA |
| Clopidogrel and Acetylsalicylic acidAlso: Plavix, AspirinThis group will receive a 300 mg loading dose of clopidogrel on the day of randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21. | Drug | Clopidogrel/ASA |
Primary outcome
High on-treatment platelet reactivity (HOPR) defined as P2Y12 reaction unit (PRU)> 208 measured by VerifyNow® assay at 90 days
Time frame: 90 days
24 secondary outcomes
HOPR at 90 days in subjects carrying genetic variants which affected Clopidogrel metabolism.
Time frame: 90 days
New vascular events defined as any event of the following: Any stroke (ischemic or hemorrhage).
Time frame: 90 days, 6 months, 1 year
New composite clinical vascular events (ischemic stroke/ hemorrhagic stroke/TIA/ myocardial infarction/ vascular death) as a cluster.
Time frame: 90 days, 6 months, 1 year
High on-treatment platelet reactivity defined as PRU> 208 measured by VerifyNow® assay.
Time frame: 2hours, 24 hours, 7 days
High on-treatment platelet reactivity defined as Aspirin reactivity unit (ARU)> 555 measured by VerifyNow® assay.
Time frame: 7 days
HOPR defined as Maximum Amplitude-adenosine diphosphate (MA-ADP)>47 measured by Thrombelastography Platelet Mapping Assay (TEG) using the inducer of adenosine diphosphate.
Time frame: 90 days
Residual platelet reactivity defined as the value of PRU.
Time frame: 2hours, 24 hours, 7 days, 90 days
Residual platelet reactivity defined as the value of Aspirin reaction unit (ARU).
Time frame: 7days
Residual platelet reactivity defined as the value of MA-ADP.
Time frame: 7days, 90 days
Residual platelet reactivity defined as the value of Maximum Amplitude- acetylsalicylic acid (MA-AA) measured by TEG.
Time frame: 7days
Residual platelet reactivity change from baseline in PRU.
Time frame: 2hours, 24 hours, 7 days, 90 days
Residual platelet reactivity change from baseline in ARU.
Time frame: 7 days
The inhibition of platelet aggregation (IPA) measured by VerifyNow® assay.
Time frame: 2hours, 24 hours, 7 days, 90 days
The TEG-platelet inhibition(TPI)measured by TEG.
Time frame: 7 days, 90 days
Platelet inhibition change from baseline in IPA.
Time frame: 2hours, 24 hours, 7 days, 90 days
Platelet inhibition change from baseline in TPI.
Time frame: 7 days, 90 days
Residual platelet reactivity detected by AspirinWorks.
Time frame: 7days
Residual platelet reactivity detected by PL Platelet Analyser (SINNOWA®).
Time frame: 7days, 90days
Modified Rankin Scale score changes (continuous) and dichotomized at percentage with score 0-2 vs. 3-6.
Time frame: 90 days, 6 months, 1 year
Further efficacy exploratory analysis:Impairment (changes in NIHSS scores at 90 days, 6 months, 1 year follow-up)
Time frame: 90 days, 6 months, 1 year
Further efficacy exploratory analysis:Quality of Life (The EuroQol-5D 3 level version[EQ-5D-3L]scale).
Time frame: 90 days, 6 months, 1 year
Major bleed (PLATO definition), including fatal/life-threatening and other.
Time frame: 90 days, 6 months, 1 year
Intracranial hemorrhagic events.
Time frame: 90 days, 6 months, 1 year
Total mortality.
Time frame: 90 days, 6 months, 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Derived from this study: PubMed 32587571Yang Y, Chen W, Pan Y, Yan H, Meng X, Liu L, Wang Y, Wang Y. Ticagrelor Is Superior to Clopidogrel in Inhibiting Platelet Reactivity in Patients With Minor Stroke or TIA. Front Neurol. 2020 Jun 10;11:534. doi: 10.3389/fneur.2020.00534. eCollection 2020.
- Derived from this study: PubMed 32052517Yang Y, Chen W, Meng X, Liu L, Wang Y, Pan Y, Wang Y. Impact of smoking on platelet function of ticagrelor versus clopidogrel in minor stroke or transient ischaemic attack. Eur J Neurol. 2020 May;27(5):833-840. doi: 10.1111/ene.14171. Epub 2020 Mar 8.
- Derived from this study: PubMed 31171523Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y; PRINCE Protocol Steering Group. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. BMJ. 2019 Jun 6;365:l2211. doi: 10.1136/bmj.l2211.
- Derived from this study: PubMed 28381198Wang Y, Lin Y, Meng X, Chen W, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Liu L, Zhao X, Wang Y; PRINCE Protocol Steering Group. Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design. Int J Stroke. 2017 Apr;12(3):321-325. doi: 10.1177/1747493017694390. Epub 2017 Jan 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ticagrelor and Acetylsalicylic acid and Clopidogrel and Acetylsalicylic acid in people with Stroke and Ischemic Attack, Transient, run by Beijing Tiantan Hospital at 25 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
High on-treatment platelet reactivity (HOPR) defined as P2Y12 reaction unit (PRU)> 208 measured by VerifyNow® assay at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02506140, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.