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 5, 2019
Last Update Posted : March 15, 2022
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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 |
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 (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 |

Arm | Intervention/treatment |
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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:
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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:
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:
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- 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.
- Number of Participants With All-cause Mortality [ Time Frame: 2-year ]
- Number of Participants With Myocardial Infarction [ Time Frame: 2 year ]
- Number of Participants With New Q-wave Myocardial Infarction [ Time Frame: 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
- Number of Participants With a Stroke [ Time Frame: 2 year ]
- Number of Participants With a Myocardial Revascularisation [ Time Frame: 2 year ]
- Number of Participants With a Definite Stent Thrombosis [ Time Frame: 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:
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Type 3a:
- Overt bleeding + Hb drop of 3 to < 5 g/dL (provided Hb drop is related to bleed)
- Any transfusion with overt bleeding
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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
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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
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Type 5a:
• Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious
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Type 5b:
- Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-"All comer" patients
- Age ≥18 years;
- 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);
- Able to provide informed consent and willing to participate in 2 year follow- up period.
Exclusion Criteria:
- Known intolerance to aspirin, P2Y12 inhibitors, bivalirudin, stainless steel or biolimus;
- 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;
- Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);
- 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;
- Need for chronic oral anti-coagulation therapy;
- Active major bleeding or major surgery within the last 30 days;
- Known history of intracranial haemorrhagic stroke or intra-cranial aneurysm;
- Known stroke (any type) within the last 30 days;
- Known pregnancy at time of randomisation;
- Female who is breastfeeding at time of randomisation;
- Currently participating in another trial and not yet at its primary endpoint.

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

Study Director: | Ernest Spitzer, MD | European Cardiovascular Research Institute | |
Principal Investigator: | Stephan Windecker, Prof. MD | Inselspital, University Hospital Bern, Switzerland |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | ECRI bv |
ClinicalTrials.gov Identifier: | NCT01813435 |
Other Study ID Numbers: |
ECRI-12-001, 02EU11 |
First Posted: | March 19, 2013 Key Record Dates |
Results First Posted: | July 5, 2019 |
Last Update Posted: | March 15, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
CAD ACS All comers DAPT PCI |
Coronary Artery Disease Coronary Disease Myocardial Ischemia 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 |