GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation

Coronary Artery Disease (CAD) Clinical Trial

Official title:

GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01813435
• Other study ID #: ECRI-12-001, 02EU11
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2013
• Est. completion date: April 26, 2018

Study information

• Verified date: March 2022
• Source: ECRI bv
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

The study objective is to determine in all-comers patients undergoing percutaneous coronary intervention (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 myocardial infarction (MI) compared to treatment with 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. The study design is an investigator-initiated, prospective randomised, multi-centre, multi-national, open-label 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15991
• Est. completion date: April 26, 2018
• Est. primary completion date: November 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)

Intervention

Drug:
• 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.
• 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
• 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

Locations

Country	Name	City	State
Australia	Research centre Brisbane, 6101	Brisbane
Australia	Research centre Melbourne, 6104	Melbourne
Australia	Research centre Melbourne, 6105	Melbourne
Austria	Research centre Graz, 4305	Graz
Austria	Rsearch centre Innsbruck, 4303	Innsbruck
Austria	Research centre Linz, 4304	Linz
Austria	Research centre Vienna, 4301	Vienna
Austria	Research centre Vienna, 4302	Vienna
Belgium	Research centre Aalst, 3201	Aalst
Belgium	Research centre Aalst, 3206	Aalst
Belgium	Research centre Bonheiden, 3204	Bonheiden
Belgium	Research centre Charleroi, 3202	Charleroi
Belgium	Research centre Genk, 3205	Genk
Belgium	Research centre Hasselt, 3203	Hasselt
Brazil	Research centre Rio de Janeiro, 5503	Rio de Janeiro
Brazil	Research centre Rio de Janeiro, 5504	Rio de Janeiro
Brazil	Research centre Sao Paulo, 5501	Sao Paulo
Brazil	Research centre Sao Paulo, 5502	Sao Paulo
Brazil	Research centre Uberlândia, 5505	Uberlândia
Bulgaria	Research centre Burgas, 9902	Burgas
Bulgaria	Research centre Plovdiv, 9905	Plovdiv
Bulgaria	Research centre Sofia, 9901	Sofia
Bulgaria	Research centre Sofia, 9903	Sofia
Bulgaria	Research centre Sofia, 9904	Sofia
Bulgaria	Research centre Sofia, 9907	Sofia
Bulgaria	Research centre Sofia, 9908	Sofia
Bulgaria	Research centre Varna, 9906	Varna
Canada	Research centre Newmarket, 1003	Newmarket
Canada	Research centre Quebec, 1001	Quebec
Denmark	Research centre Copenhagen, 4501	Copenhagen
Denmark	Research centre Roskilde, 4503	Roskilde
France	Research centre Aix en Provence, 3311	Aix en Provence
France	Research centre Caen, 3308	Caen
France	Research centre Caen, 3309	Caen
France	Research centre Clermont-Ferrand, 3303	Clermont-Ferrand
France	Research centre Dijon, 3313	Dijon
France	Research centre Grenoble, 3312	Grenoble Cedex
France	Research centre Lyon, 3316	Lyon
France	Research centre Nancy, 3314	Nancy
France	Research centre Paris, 3301	Paris
France	Research centre Paris, 3305	Paris
France	Research centre Rouen, 3307	Rouen
France	Research centre Saint Etienne, 3310	Saint Etienne
France	Research centre Toulouse, 3302	Toulouse
Germany	Research centre Bad Krozingen, 4904	Bad Krozingen
Germany	Research centre Bad Nauheim, 4902	Bad Nauheim
Germany	Research centre Berlin, 4918	Berlin
Germany	Research centre Bonn, 4911	Bonn
Germany	Research centre Dresden, 4908	Dresden
Germany	Research centre Essen, 4903	Essen
Germany	Research centre Fulda, 4905	Fulda
Germany	Research centre Giessen 4901	Giessen
Germany	Research centre Göttingen, 4907	Göttingen
Germany	Research centre Landshut, 4909	Landshut
Germany	Research centre Lubeck, 4917	Lubeck
Germany	Research centre Mainz, 4910	Mainz
Germany	Research centre Mannheim, 4912	Mannheim
Germany	Research centre Mönchengladbach, 4915	Mönchengladbach
Germany	Research centre Neuss, 4916	Neuss
Germany	Research centre Tubingen, 4914	Tubingen
Germany	Research centre Villingen - Schwenningen, 4919	Villingen - Schwenningen
Hungary	Research centre Balatonfüred, 3608	Balatonfüred
Hungary	Research centre Budapest, 3602	Budapest
Hungary	Research centre Budapest, 3603	Budapest
Hungary	Research centre Debrecen, 3607	Debrecen
Hungary	Research centre Gyula, 3606	Gyula
Hungary	Research centre Nyíregyháza, 3605	Nyíregyháza
Hungary	Research centre Pécs, 3604	Pécs
Hungary	Research centre szeged, 3601	Szeged
Italy	Research centre Arezzo, 3902	Arezzo
Italy	Research centre Brescia, 3912	Brescia
Italy	Research centre Ferrara, 3905	Ferrara
Italy	Research centre Milano, 3901	Milano
Italy	Research centre Pavia, 3903	Pavia
Italy	Research centre Terni, 3909	Terni
Netherlands	Research centre Alkmaar, 3106	Alkmaar
Netherlands	OLVG Research centre Amsterdam, 3104	Amsterdam
Netherlands	UMCG Groningen, 3108	Groningen
Netherlands	Research centre Leeuwarden, 3102	Leeuwarden
Netherlands	Research centre Nieuwegein, 3107	Nieuwegein
Netherlands	Research centre Nijmegen, 3105	Nijmegen
Netherlands	EMC Rotterdam, 3101	Rotterdam
Netherlands	Maasstad Rotterdam, 3103	Rotterdam
Netherlands	Research centre Tilburg, 3109	Tilburg
Poland	Research centre Chrzanow, 4802	Chrzanow
Poland	Research centre Dabrowa Gornicza, 4801	Dabrowa Gornicza
Poland	Research centre Kedzierzyn-Kozle, 4805	Kedzierzyn-Kozle
Poland	Research centre Krakov, 4807	Krakov
Poland	Research centre Mielec, 4809	Mielec
Poland	Research centre Nysa, 4808	Nysa
Poland	Research centre Ustron, 4803	Ustron
Portugal	Research centre Gaia, 3501	Gaia
Portugal	Research centre Lisbon, 3503	Lisbon
Portugal	Research centre Lisbon, 3504	Lisbon
Portugal	Research centre Lisbon, 3505	Lisbon
Singapore	Research centre Singapore, 6501	Singapore
Singapore	Research centre Singapore, 6502	Singapore
Spain	Research centre Barcelona, 3401	Barcelona
Spain	Research centre Barcelona, 3403	Barcelona
Spain	Research centre Barcelona, 3405	Barcelona
Spain	Research centre Huelva, 3408	Huelva
Spain	Research centre Madrid 3410	Madrid
Spain	Research centre Madrid, 3402	Madrid
Spain	Research centre Madrid, 3407	Madrid
Spain	Research centre Madrid, 3409	Madrid
Spain	Research centre Vigo, 3404	Vigo
Switzerland	Research centre Bern, 4106	Bern
Switzerland	Research centre Bern, 4107	Bern
Switzerland	Research centre Geneva, 4101	Geneva
Switzerland	Research centre Lausanne, 4104	Lausanne
Switzerland	Research centre Liestal, 4108	Liestal
Switzerland	Research centre Lugano, 4105	Lugano
United Kingdom	Research centre Belfast, 4420	Belfast
United Kingdom	Research Centre Belfast, 4423	Belfast
United Kingdom	Research centre Blackburn, 4404	Blackburn
United Kingdom	Research centre Blackpool, 4408	Blackpool
United Kingdom	Research centre Bournemouth, 4418	Bournemouth
United Kingdom	Research centre Brighton, 4405	Brighton
United Kingdom	Research centre Cambridge, 4417	Cambridge
United Kingdom	Research centre Cardiff, 4402	Cardiff
United Kingdom	Research centre Glasgow, 4407	Glasgow
United Kingdom	Research centre Leicester, 4421	Leicester
United Kingdom	Research centre Liverpool, 4001	Liverpool
United Kingdom	Research centre Manchester, 4403	Manchester
United Kingdom	Research centre Manchester, 4406	Manchester
United Kingdom	Research centre Newcastle, 4413	Newcastle
United Kingdom	Research centre Rhyl, 4414	Rhyl
United Kingdom	Research centre Southampton, 4415	Southampton
United Kingdom	Research centre Stevenage, 4412	Stevenage
United Kingdom	Research centre Wolverhampton, 4422	Wolverhampton

Sponsors (4)

Lead Sponsor	Collaborator
ECRI bv	AstraZeneca, Biosensors International, The Medicines Company

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Denmark,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Singapore,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 year
Secondary	Number of Participants With All-cause Mortality		2-year
Secondary	Number of Participants With Myocardial Infarction		2 year
Secondary	Number of Participants With New Q-wave Myocardial Infarction		2-year
Secondary	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	2-year
Secondary	Number of Participants With a Stroke		2 year
Secondary	Number of Participants With a Myocardial Revascularisation		2 year
Secondary	Number of Participants With a Definite Stent Thrombosis		2 year
Secondary	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	2 year

External Links

•   Pubmed Identifier 30166073