To determine in all-comers patients undergoing 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…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years
post randomisation.
Secondary outcome
The composite of investigator-reported BARC3 or BARC5 bleeding according to
BARC definitions up to 2 years post randomisation.
Background summary
Atherosclerosis and coronary artery thrombosis are a major cause of premature
death worldwide, and are
an important source of loss of disability-adjusted life years.1,2 ,3 Treatment
goals for patients with coronary
artery disease (CAD) and ACS after PCI may improve the survival and a
reduction in the risk of myocardial infarction (MI)
and symptoms of coronary disease
Study objective
To determine in all-comers patients undergoing 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 MI compared to treatment with 12
months of standard dual anti platelet therapy (DAPT) followed by aspirin
monotherapy In some participating centers patients are approached with the
request to determine using the reactivity of platelets during the 3, 6, 12
and/or 18 month outpatient monitoring decrease in a blood sample
Study design
Investigator-initiated, prospective randomised, multi-centre, multi-national,
openlabel
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
May 2017:
A small sub-study of Global Leaders (GLASSY) will start mid-May
Objectives and Ethical considerations of the substudy:
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.
The substudy is simply based on an independent assessment of clinical events
using source documentation of the main study. There will be no additional risks
or burden for the patients. Participants will also not derive immediate benefit
from the results of this study; however, its findings will help to improve the
quality of clinical research with consequent advantage for the entire community
including patients and physicians. So far, indeed, the impact of CEC on the
quality of trial results has never been assessed. GLASSY represents the first
systematic attempt to establish whether the CEC-adjudication process is
essential or rather dispensable for the conduct of large randomized clinical
trials. Additional potential benefits are mainly related to a better
understanding of the results of the main trial through the categorization of
the type of mortality, MI and bleeding events.
Intervention
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.
Reference treatment strategy
ACS patients incl. unstable angina (UA) patients: ASA and ticagrelor for 12
months followed by 12 months of ASA monotherapy.
Stable CAD patients*: ASA and clopidogrel for 12 months followed by 12 months
of ASA monotherapy.
* Biomarker negative, no clinical signs and/or symptoms of ongoing myocardial
ischemia.
All patients will receive a BioMatrix family drug-eluting stent during the
index PCI.
CONFIDENTIAL
GLOBAL LEADERS Protocol
Global Leaders Protocol Version: Final 1.1 Page 9 of 93
ECRI Date: 14 Jan. 2013
All patients will receive bivalirudin during the index procedure in countries
where it is available.
Note: After 2 years, the medical treatment is left to the discretion of the
physician
In a subgroup of patients (n = 2455), the platelet reactivity will be analysed
at 3,6,11 and/or 18 months after the index procedure.
Study burden and risks
Risks PCI treatment:
Risks are comparable to the standard PCI treatment.
Side effects to study medication:
bleedings
allergy to study medication and shortness of breath
less protection in anti trombotic treatment in the treatment group
Westblaak 92
Rotterdam 3012 KM
NL
Westblaak 92
Rotterdam 3012 KM
NL
Listed location countries
Age
Inclusion criteria
*Real world, 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 in a vessel with a reference vessel diameter of at least 2.25 mm (no limitation on the number of treated lesions, and vessels, and 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 the time of randomisation.;11. Currently participating in another trial and not yet at its primary endpoint.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-003515-58-NL |
| CCMO | NL43637.078.13 |