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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01813435
Recruitment Status : Completed
First Posted : March 19, 2013
Results First Posted : July 5, 2019
Last Update Posted : August 1, 2019
Sponsor:
Collaborators:
Biosensors International
AstraZeneca
The Medicines Company
Information provided by (Responsible Party):
ECRI bv

Tracking Information
First Submitted Date  ICMJE February 12, 2013
First Posted Date  ICMJE March 19, 2013
Results First Submitted Date  ICMJE December 21, 2018
Results First Posted Date  ICMJE July 5, 2019
Last Update Posted Date August 1, 2019
Actual Study Start Date  ICMJE July 1, 2013
Actual Primary Completion Date November 9, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2013)
Composite of All-cause Mortality or Non-fatal New Q-wave MI [ Time Frame: 2 year ]
The composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
  • 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:
    • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2013)
Bleeding [ Time Frame: 2-year ]
The composite of investigator-reported BARC3 or BARC5 bleeding according to BARC definitions up to 2 years post randomisation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 14, 2013)
  • Additional Endpoints [ Time Frame: 2-year ]
    All-cause mortality
  • Additional Endpoints [ Time Frame: 2-year ]
    Non-fatal new Q-wave MI
  • Additional Endpoint [ Time Frame: 2-year ]
    Ischemic stroke, including stroke of undetermined cause
  • Additional Endpoint [ Time Frame: 2-year ]
    Haemorrhagic stroke
  • Additional Endpoint [ Time Frame: 2-year ]
    Composite of all-cause mortality, stroke and non-fatal new Q-wave MI
  • Additional Endpoints [ Time Frame: 2-year ]
    Coronary revascularisation
  • Additional Endpoint [ Time Frame: 2-year ]
    Definite Stent Thrombosis according to the Academic Research Consortium
 
Descriptive Information
Brief Title  ICMJE GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
Official Title  ICMJE GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
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
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Coronary Artery Disease (CAD)
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)

    Interventions:
    • Drug: Ticagrelor
    • Drug: Acetylsalicylic Acid
  • 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

    Interventions:
    • Drug: Ticagrelor
    • Drug: Acetylsalicylic Acid
    • Drug: Clopidogrel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2019)
15991
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2013)
16000
Actual Study Completion Date  ICMJE April 26, 2018
Actual Primary Completion Date November 9, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Netherlands,   Poland,   Portugal,   Singapore,   Spain,   Switzerland,   United Kingdom
Removed Location Countries Romania,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT01813435
Other Study ID Numbers  ICMJE ECRI-12-001, 02EU11
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party ECRI bv
Study Sponsor  ICMJE ECRI bv
Collaborators  ICMJE
  • Biosensors International
  • AstraZeneca
  • The Medicines Company
Investigators  ICMJE
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
PRS Account ECRI bv
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP