GLOBAL LEADERS Adjudication Sub-Study (GLASSY)

July 31, 2020 updated by: University Hospital Inselspital, Berne
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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

7365

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria
        • Wilhelminenspital 1160
  • Belgium
      • Bonheiden, Belgium
        • Research centre Bonheiden 3204
      • Charleroi, Belgium
        • Research centre Charleroi 3202
      • Genk, Belgium
        • Research centre Genk 3205
      • Hasselt, Belgium
        • Research centre Hasselt 3203
  • Bulgaria
      • Sofia, Bulgaria
        • Research centre Sofia, 9901
  • Germany
      • Bad Nauheim, Germany
        • Research centre Bad Nauheim 4902
      • Essen, Germany
        • Research centre Essen 4903
  • Italy
      • Arezzo, Italy
        • Research centre Arezzo 3902
      • Ferrara, Italy
        • Research centre Ferrara 3905
      • Pavia, Italy
        • Research centre Pavia 3903
      • Terni, Italy
        • Research centre Terni 3909
  • Netherlands
      • Amsterdam, Netherlands
        • Research centre Amsterdam 3104
      • Rotterdam, Netherlands
        • Research centre Rotterdam 3101
  • Poland
      • Chrzanów, Poland
        • Research centre Chrzanow 4802
      • Dąbrowa Górnicza, Poland
        • Research centre Dabrowa Gornicza 4801
      • Kraków, Poland
        • Research centre Krakov 4807
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital Bern University Hospital
  • United Kingdom
      • Blackburn, United Kingdom
        • Research centre Blackburn 4404

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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)

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: 24 months or at earlier time point
Any death
24 months or at earlier time point
Non-fatal MI
Time Frame: 24 months or at earlier time point
Any non-fatal MI
24 months or at earlier time point
Non-fatal stroke
Time Frame: 24 months or at earlier time point
Any non-fatal stroke (i.e. including both ischemic and haemorrhagic)
24 months or at earlier time point
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.
24 months or at earlier time point
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
24 months or at earlier time point
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
24 months or at earlier time point
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
24 months or at earlier time point

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

European Cardiovascular Research Center

Investigators

  • Study Chair: Stephan Windecker, MD, Inselspital Bern University Hospital
  • Principal Investigator: Marco Valgimigli, MD, Inselspital Bern University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 1, 2017

Primary Completion (ACTUAL)

December 30, 2019

Study Completion (ACTUAL)

May 30, 2020

Study Registration Dates

First Submitted

July 19, 2017

First Submitted That Met QC Criteria

July 24, 2017

First Posted (ACTUAL)

July 27, 2017

Study Record Updates

Last Update Posted (ACTUAL)

August 3, 2020

Last Update Submitted That Met QC Criteria

July 31, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 039_2013_Substudy

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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