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BMJ Open. 2019 Mar 9;9(3):e026053. doi: 10.1136/bmjopen-2018-026053.

Rationale and design of a prospective substudy of clinical endpoint adjudication processes within an investigator-reported randomised controlled trial in patients with coronary artery disease: the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY).

Author information

1
University of Pavia, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
2
Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy.
3
Department of Cardiology, Cork University Hospital Group, Cork, Ireland.
4
Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, Belgium.
5
Department of Cardiology, Imperial College of London, London, UK.
6
Department of Cardiology, Jessa Hospital, Hasselt, Belgium.
7
Department of Cardiology, Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
8
Department of Cardiology, Imelda Hospital, Bonheiden, Belgium.
9
Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
10
Center of Cardiovascular Research and Development, American Heart of Poland, Katowice, Poland.
11
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
12
Department of Cardiology, S. Maria University-Hospital, Terni, Italy.
13
3rd Med Department, Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.
14
Department of Cardiology, OLVG, Amsterdam, The Netherlands.
15
Center for Cardiovascular Research and Development, American Heart of Poland, Poland, Poland.
16
Department of Cardiology, Azienda Toscana USL Sudest, Arezzo, Italy.
17
Department of Cardiology, Azienda Ospedaliero Universitaria di Ferrara Arcispedale Sant'Anna, Cona, Italy.
18
Jagiellonian University Medical College, The John Paul II Hospital, Krakow, Poland.
19
Department of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
20
Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium.
21
Department of Cardiology, Adzhibadem Siti Klinik Surdechno-sudovi Center, Sofia, Bulgaria.
22
Department of Cardiology, East Lancashire Hospitals NHS Trust, Blackburn, UK.
23
Department of Cardiology and Angiology, Contilia Heart and Vascular Centre, Essen, Germany.
24
Department of Cardiology, PAKS Kozle, Kozle, Poland.
25
Kerckhoff Heart Center, Bad Nauheim, Germany.
26
Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France.
27
CTU, Institute of Social and Preventive Medicine and Clinical Trials Unit, Bern, Switzerland.
28
Department of Medicine, Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Canada.
29
Department of Cardiology, Inselspital Universitatsspital Bern, Bern, Switzerland.
#
Contributed equally

Abstract

INTRODUCTION:

The GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias.

METHODS AND ANALYSIS:

We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events.

ETHICS AND DISSEMINATION:

GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects.

TRIAL REGISTRATION NUMBER:

NCT01813435.

KEYWORDS:

coronary heart disease; coronary intervention; ischaemic heart disease; myocardial infarction

PMID:
30852547
DOI:
10.1136/bmjopen-2018-026053
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Conflict of interest statement

Competing interests: SL reports personal fees for advisory board participation from AstraZeneca, Chiesi and The Medicine Company. M Val reports grants from The Medicines Company, grants from Terumo, during the study; grants from AstraZeneca, and personal fees from Terumo, St Jude Vascular and Abbott Vascular, outside the submitted work.

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