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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01813435




Registration number
NCT01813435
Ethics application status
Date submitted
12/02/2013
Date registered
19/03/2013
Date last updated
1/08/2019

Titles & IDs
Public title
GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
Scientific title
GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
Secondary ID [1] 0 0
ECRI-12-001, 02EU11
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease (CAD) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ticagrelor
Treatment: Drugs - Acetylsalicylic Acid
Treatment: Drugs - Clopidogrel

Experimental: 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.
Dosage and frequency:
Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- = 100 mg qd)

Active Comparator: Reference treatment strategy - Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(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.
Dosage and frequency:
Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- = 100 mg qd) Clopidogrel: 75 mg qd


Treatment: Drugs: Ticagrelor
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.

Treatment: Drugs: Acetylsalicylic Acid
Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy

Treatment: Drugs: Clopidogrel
Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a Composite of All-cause Mortality or Non-fatal New Q-wave Myocardial Infarction (MI) - Number of Participants with a composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.
Timepoint [1] 0 0
2 year
Secondary outcome [1] 0 0
Number of Participants With All-cause Mortality
Timepoint [1] 0 0
2-year
Secondary outcome [2] 0 0
Number of Participants With Myocardial Infarction
Timepoint [2] 0 0
2 year
Secondary outcome [3] 0 0
Number of Participants With New Q-wave Myocardial Infarction
Timepoint [3] 0 0
2-year
Secondary outcome [4] 0 0
Number of Participants With a Composite of All-cause Mortality, Stroke, or New Q-wave Myocardial Infarction - shown are the first event per event type for each patient only. Multiple events of the same type within the same patient are disregarded
Timepoint [4] 0 0
2-year
Secondary outcome [5] 0 0
Number of Participants With a Stroke
Timepoint [5] 0 0
2 year
Secondary outcome [6] 0 0
Number of Participants With a Myocardial Revascularisation
Timepoint [6] 0 0
2 year
Secondary outcome [7] 0 0
Number of Participants With a Definite Stent Thrombosis
Timepoint [7] 0 0
2 year
Secondary outcome [8] 0 0
Number of Participants With a Bleeding Academic Research Consortium (BARC) 3 or 5 Bleeding - BARC definition. We only considered BARC 3 or 5 for this secondary safety endpoint.
Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with:
Type 3a:
Overt bleeding + Hb drop of 3 to < 5 g/dL (provided Hb drop is related to bleed)
Any transfusion with overt bleeding
Type 3b:
Overt bleeding + Hb drop =5 g/dL (provided Hb drop is related to bleed)
Cardiac tamponade
Bleeding requiring surgical intervention (excluding dental/nasal/skin/haemorrhoid)
Bleeding requiring intravenous vasoactive agents
Type 3c:
Intracranial haemorrhage (does not include microbleeds or haemorrhagic transformation, does include intraspinal)
Subcategories confirmed by autopsy or imaging or lumbar puncture
Intraocular bleed compromising vision. Type 5: Fatal bleeding
Type 5a:
• Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious
Type 5b:
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation
Timepoint [8] 0 0
2 year

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 coronary artery bypass graft (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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research centre Brisbane, 6101 - Brisbane
Recruitment hospital [2] 0 0
Research centre Melbourne, 6104 - Melbourne
Recruitment hospital [3] 0 0
Research centre Melbourne, 6105 - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
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Austria
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Innsbruck
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Austria
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Linz
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Austria
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Vienna
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Belgium
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Aalst
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Belgium
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Bonheiden
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Charleroi
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Genk
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Hasselt
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Brazil
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Rio de Janeiro
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Sao Paulo
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Brazil
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Uberlândia
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Burgas
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Bulgaria
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Plovdiv
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Sofia
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Bulgaria
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Varna
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Canada
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Newmarket
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Quebec
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Copenhagen
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Roskilde
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France
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Aix en Provence
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France
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Caen
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Clermont-Ferrand
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Dijon
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Rouen
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Saint Etienne
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France
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Toulouse
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Germany
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Bad Krozingen
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Bad Nauheim
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Berlin
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Bonn
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Dresden
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Essen
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Fulda
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Giessen
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Göttingen
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Landshut
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Lubeck
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Neuss
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Tubingen
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Villingen - Schwenningen
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Budapest
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Gyula
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Nyíregyháza
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Brescia
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Ferrara
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Milano
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Pavia
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Groningen
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Nieuwegein
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Nijmegen
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Lausanne
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Liestal
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Switzerland
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Lugano
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United Kingdom
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Belfast
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Blackburn
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Blackpool
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Bournemouth
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Brighton
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Cambridge
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Leicester
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Liverpool
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Manchester
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Newcastle
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Rhyl
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Southampton
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United Kingdom
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Stevenage
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United Kingdom
State/province [104] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ECRI bv
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Biosensors International
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
AstraZeneca
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
The Medicines Company
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
After a stent procedure, it is common practice to prescribe anti-platelet medication to
prevent the blood from clotting. The main objective of this study is to determine if there is
a better medication strategy to prevent blood from clotting and at the same time minimising
the number of complications.

There are two medication strategies:

- Study group: Dual anti-platelet therapy (ticagrelor combined with aspirin) for 1 month,
and then ticagrelor alone for another 23 months OR

- Control group: Standard treatment, being dual anti-platelet therapy (ticagrelor or
clopidogrel combined with aspirin) for 12 months, and then aspirin alone indefinitely
Trial website
https://clinicaltrials.gov/show/NCT01813435
Trial related presentations / publications
Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Möllmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Windecker S; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018 Sep 15;392(10151):940-949. doi: 10.1016/S0140-6736(18)31858-0. Epub 2018 Aug 27.
Public notes

Contacts
Principal investigator
Name 0 0
Patrick Serruys, Prof. MD.
Address 0 0
Erasmus Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications