NCT02506140

Brief 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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
675

participants targeted

Target at P75+ for phase_2 stroke

Timeline
Completed

Started Aug 2015

Geographic Reach
1 country

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 19, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 23, 2015

Completed
9 days until next milestone

Study Start

First participant enrolled

August 1, 2015

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2017

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

July 24, 2020

Status Verified

December 1, 2017

Enrollment Period

1.6 years

First QC Date

July 19, 2015

Last Update Submit

July 22, 2020

Conditions

StrokeIschemic Attack, Transient

Keywords

minor stroketransient ischemic attackticagrelorclopidogreldual anti-platelet therapyplatelet reactivity

Outcome Measures

Primary Outcomes (1)

  • High on-treatment platelet reactivity (HOPR) defined as P2Y12 reaction unit (PRU)> 208 measured by VerifyNow® assay at 90 days

    90 days

Secondary Outcomes (24)

  • HOPR at 90 days in subjects carrying genetic variants which affected Clopidogrel metabolism.

    90 days

  • New vascular events defined as any event of the following: Any stroke (ischemic or hemorrhage).

    90 days, 6 months, 1 year

  • New composite clinical vascular events (ischemic stroke/ hemorrhagic stroke/TIA/ myocardial infarction/ vascular death) as a cluster.

    90 days, 6 months, 1 year

  • High on-treatment platelet reactivity defined as PRU> 208 measured by VerifyNow® assay.

    2hours, 24 hours, 7 days

  • High on-treatment platelet reactivity defined as Aspirin reactivity unit (ARU)> 555 measured by VerifyNow® assay.

    7 days

  • +19 more secondary outcomes

Study Arms (2)

Ticagrelor/ASA

EXPERIMENTAL

Drugs: Ticagrelor and Acetylsalicylic acid.

Drug: Ticagrelor and Acetylsalicylic acid

Clopidogrel/ASA

ACTIVE COMPARATOR

Drugs: Clopidogrel and Acetylsalicylic acid.

Drug: Clopidogrel and Acetylsalicylic acid

Interventions

Ticagrelor and Acetylsalicylic acidDRUG

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.

Also known as: BRILINTA, Aspirin
Ticagrelor/ASA
Clopidogrel and Acetylsalicylic acidDRUG

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.

Also known as: Plavix, Aspirin
Clopidogrel/ASA

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%).

You may not qualify if:

  • 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
  • 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.
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350005, China

Location

The Second People's Hospital of Shenzhen

Shenzhen, Guangdong, 518000, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

Location

North China University of Science And Technology Affiliated Hospital

Tangshan, Hebei, 063000, China

Location

Tangshan Gongren Hospital

Tangshan, Hebei, 063000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Wuhan Brain Hospital,General Hospital of The Yangtze River Shipping

Wuhan, Hubei, 430014, China

Location

Union Hospital,Tongji Medical College,Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Wuhan No.1 Hospital

Wuhan, Hubei, 430022, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Northern Jiangsu People's Hospital,Clinical Medical School,YangZhou University

Yangzhou, Jiangsu, 225001, China

Location

General Hospital of Shenyang Military

Shengyang, Liaoning, 110016, China

Location

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

General Hospital of TISCO

Taiyuan, Shanxi, 030003, China

Location

Taizhou First People's Hospital,Huangyan Hospital of Wenzhou Medical University

Taizhou, Zhejiang, 318020, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

Wenzhou Hospital of integrated Chinese and Western medicine

Wenzhou, Zhejiang, 325000, China

Location

Aviation General Hospital of China Medical University

Beijing, 100012, China

Location

Beijing Tian Tan Hospital, Capital Medical University

Beijing, 100050, China

Location

Dongfang Hospital Beijing University of Chinese Medicine

Beijing, 100078, China

Location

The First Hospital of Fangshan District,Beijing

Beijing, 102400, China

Location

Daping Hospital,Third Military Medical University

Chongqing, 400042, China

Location

Renji Hospital,Shanghai Jiao Tong University School of Medicine

Shanghai, 200127, China

Location

Tianjin Huanhu Hospital

Tianjin, 300350, China

Location

Related Publications (4)

  • 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.

    PMID: 32587571DERIVED

  • Yang 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.

    PMID: 32052517DERIVED

  • Wang 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.

    PMID: 31171523DERIVED

  • Wang 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.

    PMID: 28381198DERIVED

MeSH Terms

Conditions

StrokeIschemic Attack, Transient

Interventions

TicagrelorAspirinClopidogrel

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesBrain Ischemia

Intervention Hierarchy (Ancestors)

AdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsTiclopidineThienopyridinesThiophenesSulfur CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Executive Vice-President

Study Record Dates

First Submitted

July 19, 2015

First Posted

July 23, 2015

Study Start

August 1, 2015

Primary Completion

March 1, 2017

Study Completion

March 1, 2018

Last Updated

July 24, 2020

Record last verified: 2017-12

Locations

CN(25)