GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Biosensors International
AstraZeneca
The Medicines Company
Information provided by (Responsible Party):
ECRI bv
ClinicalTrials.gov Identifier:
NCT01813435
First received: February 12, 2013
Last updated: June 15, 2016
Last verified: April 2016
  Purpose

After a stent procedure, it is common practice to prescribe anti-platelet medication to prevent the blood from clotting. The main objective of this study is to determine if there is a better medication strategy to prevent blood from clotting and at the same time minimising the number of complications.

There are two medication strategies:

  • Study group: Dual anti-platelet therapy (ticagrelor combined with aspirin) for 1 month, and then ticagrelor alone for another 23 months OR
  • Control group: Standard treatment, being dual anti-platelet therapy (ticagrelor or clopidogrel combined with aspirin) for 12 months, and then aspirin alone indefinitely

Condition Intervention Phase
Coronary Artery Disease (CAD)
Drug: Ticagrelor
Drug: Acetylsalicylic Acid
Drug: Clopidogrel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparative Effectiveness of 1 Month of Ticagrelor Plus Aspirin Followed by Ticagrelor Monotherapy Versus a Current-day Intensive Dual Antiplatelet Therapy in All-comers Patients Undergoing Percutaneous Coronary Intervention With Bivalirudin and BioMatrix Family Drug-eluting Stent Use

Resource links provided by NLM:


Further study details as provided by ECRI bv:

Primary Outcome Measures:
  • Composite of all-cause mortality or non-fatal new Q-wave MI [ Time Frame: 2 year ] [ Designated as safety issue: Yes ]
    The composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.


Secondary Outcome Measures:
  • Bleeding [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    The composite of investigator-reported BARC3 or BARC5 bleeding according to BARC definitions up to 2 years post randomisation.


Other Outcome Measures:
  • All-cause mortality [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    All-cause mortality up to 2 years

  • Non-fatal new Q-wave MI [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Non-fatal new Q-wave MI up to 2 years

  • Ischemic stroke, including stroke of undetermined cause [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Ischemic stroke, including stroke of undetermined cause, up to 2 years

  • Haemorrhagic stroke [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Haemorrhagic stroke up to 2 years

  • Composite of all-cause mortality, stroke and non-fatal new Q-wave MI [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Composite of all-cause mortality, stroke and non-fatal new Q-wave MI up to 2 years

  • Coronary revascularisation [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Coronary revascularisation up to 2 years

  • Definite Stent Thrombosis [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
    Definite Stent Thrombosis up to 2 years according to the Academic Research Consortium


Enrollment: 16000
Study Start Date: May 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental treatment strategy

All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy.

Dosage and frequency:

Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd)

Drug: Ticagrelor
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.
Other Name: Brilique
Drug: Acetylsalicylic Acid
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy
Other Names:
  • Aspirin
  • B01AC06
Active Comparator: Reference treatment strategy

Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy.

Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy.

Dosage and frequency:

Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd

Drug: Ticagrelor
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.
Other Name: Brilique
Drug: Acetylsalicylic Acid
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy
Other Names:
  • Aspirin
  • B01AC06
Drug: Clopidogrel

Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy.

Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy

Other Names:
  • Plavix
  • B01AC04

Detailed Description:

The study objective is to determine in all-comers patients undergoing PCI under standardised treatment (including the BioMatrix family of drug-eluting stents and bivalirudin), whether treatment with 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy is superior with respect to the composite of all-cause mortality or non-fatal new Q-wave MI compared to treatment with 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.

The study design is an investigator-initiated, prospective randomised, multi-centre, multi-national, open-label trial to be conducted in approximately 60-80 interventional cardiology centres in Europe, North America, South America and Asia-Pacific. Patients will be randomised at a 1:1 ratio to study or reference treatment strategy.

Randomisation will occur at the time of the index procedure prior to PCI. Subjects will be stratified according to centre and according to the clinical presentation (Stable Coronary Artery Disease (CAD) vs. Acute Coronary Syndrome (ACS)).

All patients will be followed for a period of 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-"All comer" patients

  1. Age ≥18 years;
  2. Presence of one or more coronary artery stenoses of 50% or more in a native coronary artery or in a saphenous venous or arterial bypass conduit suitable for coronary stent implantation. The vessel should have a reference vessel diameter of at least 2.25 mm (no limitation on the number of treated lesions, vessels, or lesion length);
  3. Able to provide informed consent and willing to participate in 2 year follow- up period.

Exclusion Criteria:

  1. Known intolerance to aspirin, P2Y12 inhibitors, bivalirudin, stainless steel or biolimus;
  2. Known intake of a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir), as co-administration may lead to a substantial increase in exposure to ticagrelor;
  3. Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);
  4. Planned surgery, including CABG as a staged procedure (hybrid) within 12 months of the index procedure, unless dual antiplatelet therapy is maintained throughout the peri-surgical period;
  5. Need for chronic oral anti-coagulation therapy;
  6. Active major bleeding or major surgery within the last 30 days;
  7. Known history of intracranial haemorrhagic stroke or intra-cranial aneurysm;
  8. Known stroke (any type) within the last 30 days;
  9. Known pregnancy at time of randomisation;
  10. Female who is breastfeeding at time of randomisation;
  11. Currently participating in another trial and not yet at its primary endpoint.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01813435

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Locations
Australia
Research centre Brisbane, 6101
Brisbane, Australia
Research centre Melbourne, 6104
Melbourne, Australia
Research centre Melbourne, 6105
Melbourne, Australia
Austria
Research centre Graz, 4305
Graz, Austria
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Research centre Bonheiden, 3204
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Sponsors and Collaborators
ECRI bv
Biosensors International
AstraZeneca
The Medicines Company
Investigators
Study Chair: Patrick Serruys, Prof. MD. Erasmus Medical Center
Principal Investigator: Marco Valgimigli, MD Inselspital, University Hospital Bern, Switzerland
Principal Investigator: Pascal Vranckx, MD Jessa Hospital, Hasselt, Belgium
Principal Investigator: Stephan Windecker, Prof. MD Inselspital, University Hospital Bern, Switzerland
Principal Investigator: Christian Hamm, Prof. MD Kerckhoff Klinik GmbH, Germany
Principal Investigator: Peter Juni, Prof. MD University of Toronto, Canada
Principal Investigator: Gabriel Steg, Prof. MD. C.H.U. Bichat - Claude Bernard, France
Study Director: Gerrit-Anne van Es ECRI, the Netherlands
  More Information

Responsible Party: ECRI bv
ClinicalTrials.gov Identifier: NCT01813435     History of Changes
Other Study ID Numbers: ECRI-12-001, 02EU11 
Study First Received: February 12, 2013
Last Updated: June 15, 2016
Health Authority: Australia: Human Research Ethics Committee
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Ministry of Health
Canada: Health Canada
Denmark: Danish Health and Medicines Authority
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Singapore: Health Sciences Authority
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by ECRI bv:
CAD
ACS
All comers
DAPT
PCI

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Clopidogrel
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents

ClinicalTrials.gov processed this record on August 25, 2016