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Coronary Artery DiseaseGLASSYNCT03231059

GLOBAL LEADERS Adjudication Sub-Study

An observational study of Coronary Artery Disease and Platelet-aggregation Inhibitors, run by Insel Gruppe AG, University Hospital Bern at 19 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
How many people
7,365 participants
Where
19 sitesin 9 countries
Study dates
1 Jun 2017to 30 May 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients included in the GLOBAL LEADERS Trial, e.g. "All comers" with coronary artery disease requiring percutaneous coronary intervention (PCI)

Who may be able to join

  • "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.

Who cannot join

  • 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 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;
Show all 11Show fewer
  • 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

Trial locations and contacts

19 sites in 9 countries.

19 sites in 9 countries

Belgium4 sites

  • Research centre Bonheiden 3204

    Bonheiden

  • Research centre Charleroi 3202

    Charleroi

  • Research centre Genk 3205

    Genk

  • Research centre Hasselt 3203

    Hasselt

Other trials in Belgium

Italy4 sites

  • Research centre Arezzo 3902

    Arezzo

  • Research centre Ferrara 3905

    Ferrara

  • Research centre Pavia 3903

    Pavia

  • Research centre Terni 3909

    Terni

Other trials in Italy

Poland3 sites

  • Research centre Chrzanow 4802

    Chrzanów

  • Research centre Dabrowa Gornicza 4801

    Dąbrowa Górnicza

  • Research centre Krakov 4807

    Krakow

Other trials in Poland

Germany2 sites

  • Research centre Bad Nauheim 4902

    Bad Nauheim

  • Research centre Essen 4903

    Essen

Other trials in Germany

Netherlands2 sites

  • Research centre Amsterdam 3104

    Amsterdam

  • Research centre Rotterdam 3101

    Rotterdam

Other trials in Netherlands

Austria1 site

  • Wilhelminenspital 1160

    Vienna

Other trials in Austria

Bulgaria1 site

  • Research centre Sofia, 9901

    Sofia

Other trials in Bulgaria

Switzerland1 site

  • Inselspital Bern University Hospital

    Bern, 3010

Other trials in Switzerland

United Kingdom1 site

  • Research centre Blackburn 4404

    Blackburn

Other trials in United Kingdom

About this study

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.

Read the 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.

Keywords
Coronary artery disease, Percutaneous coronary intervention, Drug-eluting stent, Antiplatelet drugs, Clinical event committee
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03231059
Study groupRoleWhat they receive
Experimental treatment strategyAll patients in the treatment group received acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy
Reference treatment strategyAcute 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 being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of death, stroke, cardiac and bleeding events

    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

    Measured: 24 months

Secondary outcomes (7)

  1. Death

    Any death

    Measured: 24 months or at earlier time point

  2. Non-fatal MI

    Any non-fatal MI

    Measured: 24 months or at earlier time point

  3. Non-fatal stroke

    Any non-fatal stroke (i.e. including both ischemic and haemorrhagic)

    Measured: 24 months or at earlier time point

  4. Rates of urgent revascularization of the target vessel (Urgent TVR)

    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.

    Measured: 24 months or at earlier time point

  5. Definite, probable or possible Stent thrombosis

    Definite, probable or possible Stent thrombosis according to Academic Research Consortium (ARC) classification

    Measured: 24 months or at earlier time point

  6. Bleeding events

    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

    Measured: 24 months or at earlier time point

  7. Differences between the rates of outcomes reported by the investigators and the rates of outcomes as adjudicated by an independent clinical event committee

    Concordance between IR- and CEC- endpoints

    Measured: 24 months or at earlier time point

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2017
  2. Study start1 Jun 2017
  3. Primary completion30 Dec 2019
  4. Study completion30 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
7,365 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03231059
Sponsor's protocol ID
039_2013_Substudy
Acronym
GLASSY
Status last verified
Jul 2020
First submitted
19 Jul 2017
Last updated
3 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Vranckx P, Valgimigli M, Windecker S, Steg PG, Hamm C, Juni P, Garcia-Garcia HM, van Es GA, Serruys PW. Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial. EuroIntervention. 2016 Nov 20;12(10):1239-1245. doi: 10.4244/EIJY15M11_07.

    PubMed 26606735

  • Seltzer JH, Turner JR, Geiger MJ, Rosano G, Mahaffey KW, White WB, Sabol MB, Stockbridge N, Sager PT. Centralized adjudication of cardiovascular end points in cardiovascular and noncardiovascular pharmacologic trials: a report from the Cardiac Safety Research Consortium. Am Heart J. 2015 Feb;169(2):197-204. doi: 10.1016/j.ahj.2014.11.003. Epub 2014 Nov 10.

    PubMed 25641528

  • Lopes RD, Dickerson S, Hafley G, Burns S, Tourt-Uhlig S, White J, Newby LK, Komajda M, McMurray J, Bigelow R, Home PD, Mahaffey KW. Methodology of a reevaluation of cardiovascular outcomes in the RECORD trial: study design and conduct. Am Heart J. 2013 Aug;166(2):208-216.e28. doi: 10.1016/j.ahj.2013.05.005. Epub 2013 Jun 22.

    PubMed 23895802

  • Vranckx P, McFadden E, Cutlip DE, Mehran R, Swart M, Kint PP, Zijlstra F, Silber S, Windecker S, Serruys PW. Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation. Contemp Clin Trials. 2013 Jan;34(1):53-9. doi: 10.1016/j.cct.2012.08.012. Epub 2012 Sep 10.

    PubMed 22975439

  • Vranckx P, McFadden E, Mehran R, Cutlip DE. Clinical event committees in coronary stent trials: insights and recommendations based on experience in an unselected study population. EuroIntervention. 2012 Jul 20;8(3):368-74. doi: 10.4244/EIJV8I3A56.

    PubMed 22829511

  • Mahaffey KW, Wampole JL, Stebbins A, Berdan LG, McAfee D, Rorick TL, French JK, Kleiman NS, O'Connor CM, Cohen EA, Granger CB, Armstrong PW; APEX-AMI Investigators. Strategic lessons from the clinical event classification process for the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Contemp Clin Trials. 2011 Mar;32(2):178-87. doi: 10.1016/j.cct.2010.12.013. Epub 2011 Jan 8.

    PubMed 21220052

  • Frederich R, Alexander JH, Fiedorek FT, Donovan M, Berglind N, Harris S, Chen R, Wolf R, Mahaffey KW. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med. 2010 May;122(3):16-27. doi: 10.3810/pgm.2010.05.2138.

    PubMed 20463410

  • Kirwan BA, Lubsen J, de Brouwer S, Danchin N, Battler A, Bayes de Luna A, Dunselman PH, Glasser S, Koudstaal PJ, Sutton G, van Dalen FJ, Poole-Wilson PA; ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators. Diagnostic criteria and adjudication process both determine published event-rates: the ACTION trial experience. Contemp Clin Trials. 2007 Nov;28(6):720-9. doi: 10.1016/j.cct.2007.04.001. Epub 2007 Apr 19.

    PubMed 17509947

  • Petersen JL, Haque G, Hellkamp AS, Flaker GC, Mark Estes NA 3rd, Marchlinski FE, McAnulty JH, Greenspon AJ, Marinchak RA, Lee KL, Lamas GA, Mahaffey KW; MOST Clinical Events Committee. Comparing classifications of death in the Mode Selection Trial: agreement and disagreement among site investigators and a clinical events committee. Contemp Clin Trials. 2006 Jun;27(3):260-8. doi: 10.1016/j.cct.2006.02.002. Epub 2006 Mar 29.

    PubMed 16574497

  • Mahaffey KW, Roe MT, Dyke CK, Newby LK, Kleiman NS, Connolly P, Berdan LG, Sparapani R, Lee KL, Armstrong PW, Topol EJ, Califf RM, Harrington RA. Misreporting of myocardial infarction end points: results of adjudication by a central clinical events committee in the PARAGON-B trial. Second Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network Trial. Am Heart J. 2002 Feb;143(2):242-8. doi: 10.1067/mhj.2002.120145.

    PubMed 11835026

  • Mahaffey KW, Harrington RA, Akkerhuis M, Kleiman NS, Berdan LG, Crenshaw BS, Tardiff BE, Granger CB, DeJong I, Bhapkar M, Widimsky P, Corbalon R, Lee KL, Deckers JW, Simoons ML, Topol EJ, Califf RM; For the PURSUIT Investigators. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study. Curr Control Trials Cardiovasc Med. 2001 Jul 17;2(4):187-194. doi: 10.1186/cvm-2-4-187.

    PubMed 11806794

  • Leonardi S, Branca M, Franzone A, McFadden E, Piccolo R, Juni P, Vranckx P, Steg PG, Serruys PW, Benit E, Liebetrau C, Janssens L, Ferrario M, Zurakowski A, Diletti R, Dominici M, Huber K, Slagboom T, Buszman P, Bolognese L, Tumscitz C, Bryniarski K, Aminian A, Vrolix M, Petrov I, Garg S, Naber C, Prokopczuk J, Hamm C, Heg D, Windecker S, Valgimigli M. Comparison of Investigator-Reported and Clinical Event Committee-Adjudicated Outcome Events in GLASSY. Circ Cardiovasc Qual Outcomes. 2021 Feb;14(2):e006581. doi: 10.1161/CIRCOUTCOMES.120.006581. Epub 2021 Feb 4.

    PubMed 33535773

  • Franzone A, McFadden EP, Leonardi S, Piccolo R, Vranckx P, Serruys PW, Hamm C, Steg PG, Heg D, Branca M, Juni P, Windecker S, Valgimigli M; Collaborators. Ticagrelor alone or conventional dual antiplatelet therapy in patients with stable or acute coronary syndromes. EuroIntervention. 2020 Oct 23;16(8):627-633. doi: 10.4244/EIJ-D-20-00145.

    PubMed 32482616

  • Franzone A, McFadden E, Leonardi S, Piccolo R, Vranckx P, Serruys PW, Benit E, Liebetrau C, Janssens L, Ferrario M, Zurakowski A, Diletti R, Dominici M, Huber K, Slagboom T, Buszman P, Bolognese L, Tumscitz C, Bryniarski K, Aminian A, Vrolix M, Petrov I, Garg S, Naber C, Prokopczuk J, Hamm C, Steg PG, Heg D, Juni P, Windecker S, Valgimigli M; GLASSY Investigators. Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting. J Am Coll Cardiol. 2019 Nov 5;74(18):2223-2234. doi: 10.1016/j.jacc.2019.08.1038.

    PubMed 31672177

Questions about this trial

What is this clinical trial studying?

An observational study of Coronary Artery Disease and Platelet-aggregation Inhibitors, run by Insel Gruppe AG, University Hospital Bern at 19 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Belgium, Italy, Poland, Germany, Netherlands and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of death, stroke, cardiac and bleeding events (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03231059, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.

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GLOBAL LEADERS Adjudication Sub-Study (NCT03231059) | AzTrials