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GLOBAL LEADERS Adjudication Sub-Study (GLASSY)

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ClinicalTrials.gov Identifier: NCT03231059
Recruitment Status : Active, not recruiting
First Posted : July 27, 2017
Last Update Posted : January 16, 2019
Sponsor:
Collaborator:
European Cardiovascular Research Center
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Study Description
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Brief Summary:
The GLOBAL LEADERS Adjudication Sub-StudY, GLASSY, is based on a re-assessment of all the events reported in the dataset of the parent trial (COMPARATIVE EFFECTIVENESS OF 1 MONTH OF TICAGRELOR PLUS ASPIRIN FOLLOWED BY TICAGRELOR MONOTHERAPY VERSUS A CURRENT-DAY INTENSIVE DUAL ANTIPLATELET THERAPY IN ALL-COMERS PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION WITH BIVALIRUDIN AND BIOMATRIX FAMILY DRUG-ELUTING STENT USE) by an independent Clinical Event Committee (CEC), composed of three physicians not involved in the main trial. The substudy include the first 19 top-enrolling sites of the GLOBAL LEADERS to reach the estimated sample size of 7,186 patients for the two co-primary outcomes of death, any non-fatal myocardial infarction, any non-fatal stroke or urgent target vessel revascularization and bleeding events classified as 3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria. To ensure a comprehensive assessment of clinical events, a triggers logic is adopted to identify other potential events qualifying for study endpoints but not reported as such by local investigators.

Condition or disease
Coronary Artery Disease Platelet-aggregation Inhibitors

Detailed Description:
The GLOBAL LEADERS trial was designed to determine the benefits and risks of an antithrombotic regimen using ticagrelor 90 mg BID combined with low-dose (75 mg OD) acetylsalicylic acid (ASA) for one month followed by ticagrelor 90 mg BID alone for 23 months, compared to conventional dual antiplatelet therapy (DAPT) in all-comers patients with coronary artery disease undergoing biolimus-eluting stent implantation on bivalirudin. It was intended as a pragmatic clinical trial and, by design, endpoints included in primary and secondary analyses are only investigator-reported (IR) and will not undergo independent adjudication by a CEC. It is well known that in the absence of blinding of randomized treatment (i.e. in an open-label design such as GLOBAL LEADERS) the use of IR outcome may introduce detection and/or reporting bias. There are multiple lines of evidence indicating that central and independent adjudication of events may affect the results of a randomized trial by minimizing variability and heterogeneity inherently present when several different clinicians and data managers apply definitions of endpoints which are complex and sometimes not well known.Moreover, independent adjudication of ischaemic and bleeding endpoints may provide important mechanistic information that may deepen understanding of the primary endpoint result of the study by better characterizing component of such endpoints including, but not limited to, precise cause of death, sub-type of myocardial infarction (MI), and bleeding location. The objectives of this substudy are: to assess the impact of CEC-adjudication process on the results of the study; to quantify the added value of CEC adjudication process for endpoint reporting by evaluating the concordance between IR-reported and CEC-adjudicated events; to gather mechanistic information to aid in the interpretation of the effect of the experimental treatment in the parent trial and to identify specific subgroups of patients that could particularly benefit from the experimental therapy in terms of ischemic and bleeding events.

Study Design
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Study Type : Observational
Actual Enrollment : 7365 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: GLOBAL LEADERS Adjudication Sub-Study
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : December 30, 2019
Groups and Cohorts
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Group/Cohort
Experimental treatment strategy
All patients in the treatment group received acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy
Reference treatment strategy

Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and 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.


Outcome Measures
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Primary Outcome Measures :
  1. Composite of death, stroke, cardiac and bleeding events [ Time Frame: 24 months ]

    Death, any non-fatal MI, any non-fatal stroke (i.e. including both ischemic and haemorrhagic) or urgent target vessel revascularization (TVR) (co-primary efficacy endpoint) Bleeding 3 or 5 according to Bleeding Academic Research Consortium (BARC) definition (co-primary safety endpoint).

    Primary outcome will be defined as the occurrence of the sum of listed events



Secondary Outcome Measures :
  1. Death [ Time Frame: 24 months or at earlier time point ]
    Any death

  2. Non-fatal MI [ Time Frame: 24 months or at earlier time point ]
    Any non-fatal MI

  3. Non-fatal stroke [ Time Frame: 24 months or at earlier time point ]
    Any non-fatal stroke (i.e. including both ischemic and haemorrhagic)

  4. Rates of urgent revascularization of the target vessel (Urgent TVR) [ Time Frame: 24 months or at earlier time point ]
    One or more episodes of rest pain, presumed to be ischemic in origin which results in either urgent percutaneous coronary intervention or urgent coronary artery by pass graft. To be considered urgent, the repeat revascularization will be initiated within 24 hours of the last episode of ischemia and not be identified as planned or staged.

  5. Definite, probable or possible Stent thrombosis [ Time Frame: 24 months or at earlier time point ]
    Definite, probable or possible Stent thrombosis according to Academic Research Consortium (ARC) classification

  6. Bleeding events [ Time Frame: 24 months or at earlier time point ]
    Bleeding events according to Bleeding Academic Research Consortium (BARC), Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies To Open coronary arteries (GUSTO) classifications

  7. Differences between the rates of outcomes reported by the investigators and the rates of outcomes as adjudicated by an independent clinical event committee [ Time Frame: 24 months or at earlier time point ]
    Concordance between IR- and CEC- endpoints


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients included in the GLOBAL LEADERS Trial, e.g. "All comers" with coronary artery disease requiring percutaneous coronary intervention (PCI)
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 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
Contacts and Locations
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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): NCT03231059


Locations
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Austria
Wilhelminenspital 1160
Vienna, Austria
Belgium
Research centre Bonheiden 3204
Bonheiden, Belgium
Research centre Charleroi 3202
Charleroi, Belgium
Research centre Genk 3205
Genk, Belgium
Research centre Hasselt 3203
Hasselt, Belgium
Bulgaria
Research centre Sofia, 9901
Sofia, Bulgaria
Germany
Research centre Bad Nauheim 4902
Bad Nauheim, Germany
Research centre Essen 4903
Essen, Germany
Italy
Research centre Arezzo 3902
Arezzo, Italy
Research centre Ferrara 3905
Ferrara, Italy
Research centre Pavia 3903
Pavia, Italy
Research centre Terni 3909
Terni, Italy
Netherlands
Research centre Amsterdam 3104
Amsterdam, Netherlands
Research centre Rotterdam 3101
Rotterdam, Netherlands
Poland
Research centre Chrzanow 4802
Chrzanów, Poland
Research centre Dabrowa Gornicza 4801
Dąbrowa Górnicza, Poland
Research centre Krakov 4807
Kraków, Poland
Switzerland
Inselspital Bern University Hospital
Bern, Switzerland, 3010
United Kingdom
Research centre Blackburn 4404
Blackburn, United Kingdom
Sponsors and Collaborators
University Hospital Inselspital, Berne
European Cardiovascular Research Center
Investigators
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Study Chair: Stephan Windecker, MD Inselspital Bern University Hospital
Principal Investigator: Marco Valgimigli, MD Inselspital Bern University Hospital
More Information
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Publications:

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03231059     History of Changes
Other Study ID Numbers: 039_2013_Substudy
First Posted: July 27, 2017    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital Inselspital, Berne:
Coronary artery disease
Percutaneous coronary intervention
Drug-eluting stent
Antiplatelet drugs
Clinical event committee
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
 Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases