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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Coronary Artery Disease (CAD)

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Acetylsalicylic Acid
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental treatment strategy<br>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<br>* 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.<br>* Other names: Brilique;Drug: Acetylsalicylic Acid<br>* 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<br>* Other names: B01AC06;|
| Active Comparator: Reference treatment strategy<br>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<br>* 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.<br>* Other names: Brilique;Drug: Acetylsalicylic Acid<br>* 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<br>* Other names: B01AC06;Drug: Clopidogrel<br>* 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<br>* Other names: B01AC04;|

What is the study measuring?
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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) | 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 |  | 2-year | 
| Number of Participants With Myocardial Infarction |  | 2 year | 
| Number of Participants With New Q-wave Myocardial Infarction |  | 2-year | 
| Number of Participants With a Composite of All-cause Mortality, Stroke, or New Q-wave Myocardial Infarction | 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 |  | 2 year | 
| Number of Participants With a Myocardial Revascularisation |  | 2 year | 
| Number of Participants With a Definite Stent Thrombosis |  | 2 year | 
| Number of Participants With a Bleeding Academic Research Consortium (BARC) 3 or 5 Bleeding | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAD, ACS, All comers, DAPT, PCI