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

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ClinicalTrials.gov Identifier: NCT01813435
Recruitment Status : Completed
First Posted : March 19, 2013
Results First Posted : July 4, 2019
Last Update Posted : August 1, 2019
Sponsor:
Collaborators:
Biosensors International
AstraZeneca
The Medicines Company
Information provided by (Responsible Party):
ECRI bv

Brief Summary:

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 or disease Intervention/treatment Phase
Coronary Artery Disease (CAD) Drug: Ticagrelor Drug: Acetylsalicylic Acid Drug: Clopidogrel Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15991 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
Actual Study Start Date : July 1, 2013
Actual Primary Completion Date : November 9, 2015
Actual Study Completion Date : April 26, 2018

Resource links provided by the National Library of Medicine


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)

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of Participants With All-cause Mortality [ Time Frame: 2-year ]
  2. Number of Participants With Myocardial Infarction [ Time Frame: 2 year ]
  3. Number of Participants With New Q-wave Myocardial Infarction [ Time Frame: 2-year ]
  4. 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

  5. Number of Participants With a Stroke [ Time Frame: 2 year ]
  6. Number of Participants With a Myocardial Revascularisation [ Time Frame: 2 year ]
  7. Number of Participants With a Definite Stent Thrombosis [ Time Frame: 2 year ]
  8. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01813435


  Show 130 Study Locations
Sponsors and Collaborators
ECRI bv
Biosensors International
AstraZeneca
The Medicines Company
Investigators
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Study Chair: Patrick Serruys, Prof. MD. Erasmus Medical Center
Principal Investigator: Marco Valgimigli, Prof. 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

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ECRI bv
ClinicalTrials.gov Identifier: NCT01813435     History of Changes
Other Study ID Numbers: ECRI-12-001, 02EU11
First Posted: March 19, 2013    Key Record Dates
Results First Posted: July 4, 2019
Last Update Posted: August 1, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
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Aspirin
Clopidogrel
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
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