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

Coronary Artery Disease Clinical Trial

— POPular CABG  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02352402
• Other study ID #: POPCABG
• Secondary ID: 2014-002142-50
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2015
• Est. completion date: August 2020

Study information

• Verified date: April 2020
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 487
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Angina, Stable
• Coronary Artery Disease
• Stable Angina

Intervention

Drug:
• Ticagrelor

• Placebo

Locations

Country	Name	City	State
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	St Antonius Hospital	Nieuwegein	Utrecht
Netherlands	Radboud UMC	Nijmegen
Netherlands	Erasmus Erasmus UMC	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
J.M. ten Berg	AstraZeneca

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Willemsen LM, Janssen PWA, Hackeng CM, Kelder JC, Tijssen JGP, van Straten AHM, Soliman-Hamad MA, Deneer VHM, Daeter EJ, Sonker U, Klein P, Ten Berg JM. 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-Rationale and design of the POPular CABG trial. Am Heart J. 2020 Feb;220:237-245. doi: 10.1016/j.ahj.2019.12.001. Epub 2019 Dec 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Saphenous vein graft occlusion	As assessed with coronary computed tomography angiography or clinically indicated coronary angiography	1 year after coronary artery bypass grafting
Secondary	Saphenous vein graft failure	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	1 year after coronary artery bypass grafting
Secondary	Significant saphenous vein graft stenosis	As assessed with coronary computed tomography angiography or clinically indicated coronary angiography	1 year after coronary artery bypass grafting
Secondary	BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding	Bleeding Academic Research Consortium bleeding criteria	30 days after coronary artery bypass grafting
Secondary	BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding	Bleeding Academic Research Consortium bleeding criteria	1 year after coronary artery bypass grafting
Secondary	TIMI minor and major bleeding	Thrombolysis in Myocardial Infarction bleeding criteria	30 days after coronary artery bypass grafting
Secondary	TIMI minor and major bleeding	Thrombolysis in Myocardial Infarction bleeding criteria	1 year after coronary artery bypass grafting
Secondary	High platelet reactivity	As assessed with platelet function tests.	Within 72h before coronary artery bypass grafting
Secondary	High platelet reactivity	As assessed with platelet function tests.	3 days after coronary artery bypass grafting
Secondary	High platelet reactivity	As assessed with platelet function tests.	1 year after coronary artery bypass grafting
Secondary	Level of GDF-15	Growth differentiation factor 15 level	Within 72h before coronary artery bypass grafting
Secondary	Level of GDF-15	Growth differentiation factor 15 level	3 days after coronary artery bypass grafting
Secondary	Level of GDF-15	Growth differentiation factor 15 level	1 year after coronary artery bypass grafting
Secondary	Arterial graft occlusion	As assessed with coronary computed tomography angiography or clinically indicated coronary angiography	1 year after coronary artery bypass grafting
Secondary	All graft occlusion	As assessed with coronary computed tomography angiography or clinically indicated coronary angiography	1 year after coronary artery bypass grafting
Secondary	Significant arterial graft stenosis	As assessed with coronary computed tomography angiography or clinically indicated coronary angiography	1 year after coronary artery bypass grafting