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)
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 487
- 试验地点
- 6
- 主要终点
- Saphenous vein graft occlusion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 22 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Ticagrelor
Ticagrelor 90mg twice daily for 1 year on top of ASA
干预措施: Ticagrelor (Drug)
Placebo
Placebo matching ticagrelor 90mg twice daily on top of ASA
干预措施: Placebo (Drug)
结局指标
主要结局
Saphenous vein graft occlusion
时间窗: 1 year after coronary artery bypass grafting
As assessed with coronary computed tomography angiography or clinically indicated coronary angiography
次要结局
- Saphenous vein graft failure(1 year after coronary artery bypass grafting)
- BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding(1 year after coronary artery bypass grafting)
- TIMI minor and major bleeding(1 year after coronary artery bypass grafting)
- High platelet reactivity(1 year after coronary artery bypass grafting)
- Significant saphenous vein graft stenosis(1 year after coronary artery bypass grafting)
- Arterial graft occlusion(1 year after coronary artery bypass grafting)
- All graft occlusion(1 year after coronary artery bypass grafting)
- Level of GDF-15(1 year after coronary artery bypass grafting)
- Significant arterial graft stenosis(1 year after coronary artery bypass grafting)
研究者
J.M. ten Berg
MD, PhD, FESC, FACC
St. Antonius Hospital