POPular CABG: The Effect Of Ticagrelor On Saphenous Vein Graft Patency In Patients Undergoing Coronary Artery Bypass Grafting Surgery

Sponsor

J.M. ten Berg (Other)

Overall Status

Unknown status

CT.gov ID

NCT02352402

Collaborator

AstraZeneca (Industry)

487

Enrollment

Locations

Arms

65.1

Duration (Months)

81.2

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In the POPular CABG study we investigate if the addition of ticagrelor, a drug that inhibits blood platelets from clotting, to treatment with aspirin will reduce the rate of saphenous vein graft occlusion as assessed with coronary computed tomography angiography at 1 year after coronary artery bypass grafting surgery.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Stable Angina Acute Coronary Syndrome	Drug: Ticagrelor Drug: Placebo	Phase 3

Detailed Description

Rationale: Acetylsalicylic acid (ASA) is used to prevent the occlusion of grafts placed during coronary artery bypass grafting surgery (CABG) and to reduce the incidence of atherothrombotic events during follow-up. Graft occlusion occurs predominantly in saphenous vein grafts (SVGs) and can result in symptoms of chest pain, myocardial infarction (MI) and even death. The anti-thrombotic effect of ASA is a result of the inhibition of the generation of thromboxane A2 (TXA2) in blood platelets. Despite ASA therapy, 6.8% to 26% of SVGs occlude in the first year after CABG, mainly due to thrombus formation. This might be due to the fact that ASA is not equally effective in all patients, indicated by a substantial amount of patients that still generate TXA2 and show activated platelets, despite adequate ASA use. We hypothesize that more potent platelet inhibition by the addition of ticagrelor to standard ASA therapy could decrease the rate of SVG occlusion.

Main objective: To investigate whether a combination of ticagrelor 90mg twice daily and ASA 80mg once daily is superior to ASA 80mg once daily alone in the prevention of SVG occlusion in patients who underwent CABG with use of one or more SVGs, as assessed with coronary computed tomography angiography (CCTA) at 1 year after randomization.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial. Number of patients: Approximately 500 patients will be randomized.

Study population: Patients undergoing CABG with one or more SVGs, CABG being an isolated procedure or part of combined surgery.

Informed consent procedure, screening and sample size: We will screen patients and obtain informed consent before CABG. After CABG patients who gave informed consent are screened again to check if the patient fulfills the inclusion criteria and does not have any exclusion criteria. A total of 500 patients will receive randomized study medication after CABG.

Intervention: Patients will be randomly assigned to treatment with 90mg of ticagrelor or a matching placebo twice daily in addition to standard treatment with ASA for the duration of 1 year. Patients will be prescribed 80mg of ASA once daily according to routine clinical practice. Graft patency will be assessed with CCTA 1 year after randomization. If the patient consents to participate in the substudies, platelet function tests will be performed before surgery and 3 days and 1 year after randomization. Thirty day and one-year follow-up of clinical events will be obtained for all patients by screening the (electronic) patient file, telephonic interviews, study site visits and possibly with questionnaires.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

487 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Trial Investigating The Effect Of Ticagrelor On Saphenous Vein Graft Patency In Patients Undergoing Coronary Artery Bypass Grafting Surgery (The POPular CABG Study)

Study Start Date :

Mar 1, 2015

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ticagrelor Ticagrelor 90mg twice daily for 1 year on top of ASA	Drug: Ticagrelor Other Names: Brilique Brillinta
Placebo Comparator: Placebo Placebo matching ticagrelor 90mg twice daily on top of ASA	Drug: Placebo

Arm

Intervention/Treatment

Experimental: Ticagrelor

Ticagrelor 90mg twice daily for 1 year on top of ASA

Drug: Ticagrelor

Other Names:

Brilique

Brillinta

Placebo Comparator: Placebo

Placebo matching ticagrelor 90mg twice daily on top of ASA

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Saphenous vein graft occlusion [1 year after coronary artery bypass grafting]
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography

Secondary Outcome Measures

Saphenous vein graft failure [1 year after coronary artery bypass grafting]
Composite of saphenous vein graft occlusion as assessed with coronary computed tomography angiography or clinically indicated coronary angiography, saphenous vein graft revascularization, myocardial infarction in the myocardial territory supplied by a saphenous vein graft or sudden death
Significant saphenous vein graft stenosis [1 year after coronary artery bypass grafting]
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography
BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding [30 days after coronary artery bypass grafting]
Bleeding Academic Research Consortium bleeding criteria
BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding [1 year after coronary artery bypass grafting]
Bleeding Academic Research Consortium bleeding criteria
TIMI minor and major bleeding [30 days after coronary artery bypass grafting]
Thrombolysis in Myocardial Infarction bleeding criteria
TIMI minor and major bleeding [1 year after coronary artery bypass grafting]
Thrombolysis in Myocardial Infarction bleeding criteria
High platelet reactivity [Within 72h before coronary artery bypass grafting]
As assessed with platelet function tests.
High platelet reactivity [3 days after coronary artery bypass grafting]
As assessed with platelet function tests.
High platelet reactivity [1 year after coronary artery bypass grafting]
As assessed with platelet function tests.
Level of GDF-15 [Within 72h before coronary artery bypass grafting]
Growth differentiation factor 15 level
Level of GDF-15 [3 days after coronary artery bypass grafting]
Growth differentiation factor 15 level
Level of GDF-15 [1 year after coronary artery bypass grafting]
Growth differentiation factor 15 level
Arterial graft occlusion [1 year after coronary artery bypass grafting]
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography
All graft occlusion [1 year after coronary artery bypass grafting]
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography
Significant arterial graft stenosis [1 year after coronary artery bypass grafting]
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

More than 21 years of age
Planned coronary artery bypass grafting (CABG) with the use of 1 or more saphenous vein grafts, CABG being an isolated procedure or part of a combined aortic valce replacement surgery with bioprothesis.

Exclusion Criteria:

Unable to give informed consent or a life expectancy of less than 1 year
Concomitant valve, aorta or rhythm surgery during the same session, (excluding aortic bioprothesis)
Inability to undergo coronary computed tomography angiography, in the investigator's opinion, for instance due to severe claustrophobia or contrast allergy
Use of oral anticoagulants (acenocoumarol, phenprocoumon, dabigatran, rivaroxaban, etc) and a contraindication for discontinuation of this medication or the expectation that the patient will have an indication for the use of these drugs after surgery
Placement of a drug-eluting stent in a coronary or cerebral artery within 6 months of CABG or placement of a bare-metal stent in a coronary or cerebral artery within 1 month of CABG
Use of antiplatelet drugs other than aspirin (clopidogrel, prasugrel, ticagrelor, dipyridamol, etc.) and a contraindication for discontinuation of this medication after CABG, according to the treating physician or the investigator
Women who are known to be pregnant, who have given birth within the past 90 days or who are breastfeeding
Pre-menopausal women without adequate contraception
Severe renal function impairment requiring dialysis
Moderate or severe hepatic impairment
Active malignancy with increase in bleeding risk, in the investigator's opinion
Use of strong inhibitors of CYP3A4 (e.g. ketaconazole, clarithromycin, nefazodone, ritonavir, atazanavir)
Clinically significant out of range values for platelet count or haemoglobin at screening, in the investigator's opinion
Contraindication for the use of ticagrelor or aspirin (i.e. history of intracranial bleeding, high bleeding risk, previous allergic reaction), in the investigator's opinion
Previous inclusion in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St Antonius Hospital	Nieuwegein	Utrecht	Netherlands	3435CM
2	Catharina Ziekenhuis	Eindhoven		Netherlands	5623 EJ
3	Medisch Spectrum Twente	Enschede		Netherlands
4	Universitair Medisch Centrum Groningen	Groningen		Netherlands
5	Radboud UMC	Nijmegen		Netherlands
6	Erasmus Erasmus UMC	Rotterdam		Netherlands