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

March 13, 2022 updated by: ECRI bv

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

Study Overview

Detailed Description

The study objective is to determine in all-comers patients undergoing percutaneous coronary intervention (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 myocardial infarction (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.

Study Type

Interventional

Enrollment (Actual)

15991

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Brisbane, Australia
        • Research centre Brisbane, 6101
      • Melbourne, Australia
        • Research centre Melbourne, 6104
      • Melbourne, Australia
        • Research centre Melbourne, 6105
      • Graz, Austria
        • Research centre Graz, 4305
      • Innsbruck, Austria
        • Rsearch centre Innsbruck, 4303
      • Linz, Austria
        • Research centre Linz, 4304
      • Vienna, Austria
        • Research centre Vienna, 4301
      • Vienna, Austria
        • Research centre Vienna, 4302
      • Aalst, Belgium
        • Research centre Aalst, 3201
      • Aalst, Belgium
        • Research centre Aalst, 3206
      • Bonheiden, Belgium
        • Research centre Bonheiden, 3204
      • Charleroi, Belgium
        • Research centre Charleroi, 3202
      • Genk, Belgium
        • Research centre Genk, 3205
      • Hasselt, Belgium
        • Research centre Hasselt, 3203
      • Rio de Janeiro, Brazil
        • Research centre Rio de Janeiro, 5503
      • Rio de Janeiro, Brazil
        • Research centre Rio de Janeiro, 5504
      • Sao Paulo, Brazil
        • Research centre Sao Paulo, 5501
      • Sao Paulo, Brazil
        • Research centre Sao Paulo, 5502
      • Uberlândia, Brazil
        • Research centre Uberlândia, 5505
      • Burgas, Bulgaria
        • Research centre Burgas, 9902
      • Plovdiv, Bulgaria
        • Research centre Plovdiv, 9905
      • Sofia, Bulgaria
        • Research centre Sofia, 9901
      • Sofia, Bulgaria
        • Research centre Sofia, 9903
      • Sofia, Bulgaria
        • Research centre Sofia, 9904
      • Sofia, Bulgaria
        • Research centre Sofia, 9907
      • Sofia, Bulgaria
        • Research centre Sofia, 9908
      • Varna, Bulgaria
        • Research centre Varna, 9906
      • Newmarket, Canada
        • Research centre Newmarket, 1003
      • Quebec, Canada
        • Research centre Quebec, 1001
      • Copenhagen, Denmark
        • Research centre Copenhagen, 4501
      • Roskilde, Denmark
        • Research centre Roskilde, 4503
      • Aix en Provence, France
        • Research centre Aix en Provence, 3311
      • Caen, France
        • Research centre Caen, 3308
      • Caen, France
        • Research centre Caen, 3309
      • Clermont-Ferrand, France
        • Research centre Clermont-Ferrand, 3303
      • Dijon, France
        • Research centre Dijon, 3313
      • Grenoble Cedex, France
        • Research centre Grenoble, 3312
      • Lyon, France
        • Research centre Lyon, 3316
      • Nancy, France
        • Research centre Nancy, 3314
      • Paris, France
        • Research centre Paris, 3301
      • Paris, France
        • Research centre Paris, 3305
      • Rouen, France
        • Research centre Rouen, 3307
      • Saint Etienne, France
        • Research centre Saint Etienne, 3310
      • Toulouse, France
        • Research centre Toulouse, 3302
      • Bad Krozingen, Germany
        • Research centre Bad Krozingen, 4904
      • Bad Nauheim, Germany
        • Research centre Bad Nauheim, 4902
      • Berlin, Germany
        • Research centre Berlin, 4918
      • Bonn, Germany
        • Research centre Bonn, 4911
      • Dresden, Germany
        • Research centre Dresden, 4908
      • Essen, Germany
        • Research centre Essen, 4903
      • Fulda, Germany
        • Research centre Fulda, 4905
      • Giessen, Germany
        • Research centre Giessen 4901
      • Göttingen, Germany
        • Research centre Göttingen, 4907
      • Landshut, Germany
        • Research centre Landshut, 4909
      • Lubeck, Germany
        • Research centre Lubeck, 4917
      • Mainz, Germany
        • Research centre Mainz, 4910
      • Mannheim, Germany
        • Research centre Mannheim, 4912
      • Mönchengladbach, Germany
        • Research centre Mönchengladbach, 4915
      • Neuss, Germany
        • Research centre Neuss, 4916
      • Tubingen, Germany
        • Research centre Tubingen, 4914
      • Villingen - Schwenningen, Germany
        • Research centre Villingen - Schwenningen, 4919
      • Balatonfüred, Hungary
        • Research centre Balatonfüred, 3608
      • Budapest, Hungary
        • Research centre Budapest, 3602
      • Budapest, Hungary
        • Research centre Budapest, 3603
      • Debrecen, Hungary
        • Research centre Debrecen, 3607
      • Gyula, Hungary
        • Research centre Gyula, 3606
      • Nyíregyháza, Hungary
        • Research centre Nyíregyháza, 3605
      • Pécs, Hungary
        • Research centre Pécs, 3604
      • Szeged, Hungary
        • Research centre szeged, 3601
      • Arezzo, Italy
        • Research centre Arezzo, 3902
      • Brescia, Italy
        • Research centre Brescia, 3912
      • Ferrara, Italy
        • Research centre Ferrara, 3905
      • Milano, Italy
        • Research centre Milano, 3901
      • Pavia, Italy
        • Research centre Pavia, 3903
      • Terni, Italy
        • Research centre Terni, 3909
      • Alkmaar, Netherlands
        • Research centre Alkmaar, 3106
      • Amsterdam, Netherlands
        • OLVG Research centre Amsterdam, 3104
      • Groningen, Netherlands
        • UMCG Groningen, 3108
      • Leeuwarden, Netherlands
        • Research centre Leeuwarden, 3102
      • Nieuwegein, Netherlands
        • Research centre Nieuwegein, 3107
      • Nijmegen, Netherlands
        • Research centre Nijmegen, 3105
      • Rotterdam, Netherlands
        • EMC Rotterdam, 3101
      • Rotterdam, Netherlands
        • Maasstad Rotterdam, 3103
      • Tilburg, Netherlands
        • Research centre Tilburg, 3109
      • Chrzanow, Poland
        • Research centre Chrzanow, 4802
      • Dabrowa Gornicza, Poland
        • Research centre Dabrowa Gornicza, 4801
      • Kedzierzyn-Kozle, Poland
        • Research centre Kedzierzyn-Kozle, 4805
      • Krakov, Poland
        • Research centre Krakov, 4807
      • Mielec, Poland
        • Research centre Mielec, 4809
      • Nysa, Poland
        • Research centre Nysa, 4808
      • Ustroń, Poland
        • Research centre Ustroń, 4803
      • Gaia, Portugal
        • Research centre Gaia, 3501
      • Lisbon, Portugal
        • Research centre Lisbon, 3503
      • Lisbon, Portugal
        • Research centre Lisbon, 3504
      • Lisbon, Portugal
        • Research centre Lisbon, 3505
      • Singapore, Singapore
        • Research centre Singapore, 6501
      • Singapore, Singapore
        • Research centre Singapore, 6502
      • Barcelona, Spain
        • Research centre Barcelona, 3401
      • Barcelona, Spain
        • Research centre Barcelona, 3403
      • Barcelona, Spain
        • Research centre Barcelona, 3405
      • Huelva, Spain
        • Research centre Huelva, 3408
      • Madrid, Spain
        • Research centre Madrid 3410
      • Madrid, Spain
        • Research centre Madrid, 3402
      • Madrid, Spain
        • Research centre Madrid, 3407
      • Madrid, Spain
        • Research centre Madrid, 3409
      • Vigo, Spain
        • Research centre Vigo, 3404
      • Bern, Switzerland
        • Research centre Bern, 4106
      • Bern, Switzerland
        • Research centre Bern, 4107
      • Geneva, Switzerland
        • Research centre Geneva, 4101
      • Lausanne, Switzerland
        • Research centre Lausanne, 4104
      • Liestal, Switzerland
        • Research centre Liestal, 4108
      • Lugano, Switzerland
        • Research centre Lugano, 4105
      • Belfast, United Kingdom
        • Research centre Belfast, 4420
      • Belfast, United Kingdom
        • Research Centre Belfast, 4423
      • Blackburn, United Kingdom
        • Research centre Blackburn, 4404
      • Blackpool, United Kingdom
        • Research centre Blackpool, 4408
      • Bournemouth, United Kingdom
        • Research centre Bournemouth, 4418
      • Brighton, United Kingdom
        • Research centre Brighton, 4405
      • Cambridge, United Kingdom
        • Research centre Cambridge, 4417
      • Cardiff, United Kingdom
        • Research centre Cardiff, 4402
      • Glasgow, United Kingdom
        • Research centre Glasgow, 4407
      • Leicester, United Kingdom
        • Research centre Leicester, 4421
      • Liverpool, United Kingdom
        • Research centre Liverpool, 4001
      • Manchester, United Kingdom
        • Research centre Manchester, 4403
      • Manchester, United Kingdom
        • Research centre Manchester, 4406
      • Newcastle, United Kingdom
        • Research centre Newcastle, 4413
      • Rhyl, United Kingdom
        • Research centre Rhyl, 4414
      • Southampton, United Kingdom
        • Research centre Southampton, 4415
      • Stevenage, United Kingdom
        • Research centre Stevenage, 4412
      • Wolverhampton, United Kingdom
        • Research centre Wolverhampton, 4422

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 coronary artery bypass graft (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

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:
  • Brilique
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

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:
  • Brilique
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

Other Names:
  • Plavix
  • B01AC04

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Composite of All-cause Mortality or Non-fatal New Q-wave Myocardial Infarction (MI)
Time Frame: 2 year
Number of Participants with a composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With All-cause Mortality
Time Frame: 2-year
2-year
Number of Participants With Myocardial Infarction
Time Frame: 2 year
2 year
Number of Participants With New Q-wave Myocardial Infarction
Time Frame: 2-year
2-year
Number of Participants With a Composite of All-cause Mortality, Stroke, or New Q-wave Myocardial Infarction
Time Frame: 2-year
shown are the first event per event type for each patient only. Multiple events of the same type within the same patient are disregarded
2-year
Number of Participants With a Stroke
Time Frame: 2 year
2 year
Number of Participants With a Myocardial Revascularisation
Time Frame: 2 year
2 year
Number of Participants With a Definite Stent Thrombosis
Time Frame: 2 year
2 year
Number of Participants With a Bleeding Academic Research Consortium (BARC) 3 or 5 Bleeding
Time Frame: 2 year

BARC definition. We only considered BARC 3 or 5 for this secondary safety endpoint.

Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with:

  • Type 3a:

    • Overt bleeding + Hb drop of 3 to < 5 g/dL (provided Hb drop is related to bleed)
    • Any transfusion with overt bleeding
  • Type 3b:

    • Overt bleeding + Hb drop ≥5 g/dL (provided Hb drop is related to bleed)
    • Cardiac tamponade
    • Bleeding requiring surgical intervention (excluding dental/nasal/skin/haemorrhoid)
    • Bleeding requiring intravenous vasoactive agents
  • Type 3c:

    • Intracranial haemorrhage (does not include microbleeds or haemorrhagic transformation, does include intraspinal)
    • Subcategories confirmed by autopsy or imaging or lumbar puncture
    • Intraocular bleed compromising vision. Type 5: Fatal bleeding
    • Type 5a:

      • Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious

    • Type 5b:

      • Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Stephan Windecker, Prof. MD, Inselspital, University Hospital Bern, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2013

Primary Completion (Actual)

November 9, 2015

Study Completion (Actual)

April 26, 2018

Study Registration Dates

First Submitted

February 12, 2013

First Submitted That Met QC Criteria

March 14, 2013

First Posted (Estimate)

March 19, 2013

Study Record Updates

Last Update Posted (Actual)

March 15, 2022

Last Update Submitted That Met QC Criteria

March 13, 2022

Last Verified

March 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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