PeRcutaneous cOronary Intervention of Native Coronary arTery Versus Venous Bypass Graft in Patients With Prior CABG

Study Overview
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Brief Summary
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Multi-centre, randomised clinical trial with anticipated 17 European centres: in the Netherlands, Belgium, Germany and UK. Patients with a dysfunctional bypass graft with a clinical indication for revascularization will be randomized to either PCI of the native vessel or PCI of the dysfunctional venous bypass graft. 584 patients with a a clinical indication for percutaneous coronary intervention and a dysfunctional graft on the target vesselional venous bypass graft are planned to be enrolled during 3 years.Study objectives: to investigate the clinical and angiographic outcome of native vessel PCI compared to PCI of venous bypass graft in patients with a dysfunctional venous bypass graft with a clinical indication for revascularization. 1 year and 5 years, follow-up will be performed by means of a telephonic visit. After 3 years patients will be admitted to undergo a control invasive angiography.The CT-substudy and the PROCTOR registry is planned to be conducted too.

Detailed Description
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Multi-centre, randomised clinical trial with anticipated 17 European centres: in the Netherlands, Belgium, Germany and UK. Patients with a dysfunctional bypass graft with a clinical indication for revascularization will be randomized to either PCI of the native vessel or PCI of the dysfunctional venous bypass graft. The CT-substudy and the PROCTOR registry is planned to be conducted too (details included in the flow chart). CCTA substudy Selected patients will be approached for participation in the CCTA substudy of the trial. Participation in this substudy is optional. After written informed consent is obtained patients will undergo a CCTA in an out-patient setting. The CCTA will be performed before the PCI procedure. PROCTOR registry Patients can be approached for the registry when : PCI have been deemed clinically indicated by the local hartteam, and both the lesions in the native vessel and the dysfunctional graft have been deemed technically feasible by the local hartteam, the patient does not meet the in- and exclusion criteria for the randomized PROCTOR study or declines to participate in the randomized study. Patients will be approached for participation and will have one week to consider. Written informed consent is mandatory for participating in the registry. Patients will be followed by telephonic follow-up after 1, 3, and 5 years. No additional study procedures will be performed. Study objectives:to investigate the clinical and angiographic outcome of native vessel PCI compared to PCI of venous bypass graft in patients with a dysfunctional venous bypass graft with a clinical indication for revascularization. PROCTOR main study - Investigate the clinical outcome of native vessel PCI vs. PCI of dysfunctional venous bypass graft with a clinical indication for revascularisation CCTA substudy Investigate prognostic value of CT-derived plaque characteristics for occurrence of MACE following bypass graft PCI Investigate value of CCTA in guidance of CTO PCI procedures PROCTOR Registry - Investigate long-term clinical outcomes in patients with dysfunctional venous bypass graft and an indication for PCI whom are not included in randomised main study. All patients with a significant stenosis (>50% on coronary angiography) in a venous bypass graft discussed in the local heart team for revascularization will be screened for potential inclusion in the study. Patients will be eligible for inclusion if revascularization is deemed clinically indicated and technically feasible for PCI by the local heart team. The indication for revascularization will be based on symptoms and evidence of ischemia and viability in the target vessel territory. The lesion in the native vessel must be bypassed by a single venous graft or must be connected to a jump graft at the most distal anastomosis of that graft. In jump grafts, the lesion must be located distally to the second-to-last anastomosis. In case both the lesion in the native vessel and the lesion in the graft are deemed technically feasible for PCI, patients will be eligible for inclusion in the randomized study after consideration of in- and exclusion criteria. Patients who do not meet these criteria or decline to participate in the randomized study will be approached for inclusion in the registry. Subsequently patients will be approached for study participation. After being informed, patients will have at least 24 hours to consider participation. An independent physician will be available for extra information, if desired. After obtaining written informed consent, patients will be randomized to either native vessel PCI or PCI of the venous bypass graft. In case of PCI failure, a second attempt can be performed by the operator within one month. If feasible, it is possible to perform a second attempt in another high-volume center. When successful PCI cannot be accomplished in one or two attempts, cross-over to the other treatment arm may be used as bailout strategy to restore myocardial blood flow to the distal vascular bed of the vessel. Randomization will be performed using an interactive Web-based randomization system, Open Clinica. After 1 and 5 years, follow-up will be performed by means of a telephonic visit. After 3 years patients will be admitted to undergo a control invasive angiography.

Official Title
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PeRcutaneous cOronary Intervention of Native Coronary arTery Versus Venous Bypass Graft in Patients With Prior cORonary Artery Bypass Graft Surgery - the PROCTOR Trial

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A significant stenosis (>50% on angiography) in a venous bypass graft The native lesion must be bypassed by a single graft or must be connected to a jump graft at the most distal anastomosis of that graft In jumpgraft lesions, the lesion must be located distally to the second-to-last anastomosis Clinical indication for revascularization as determined by the local heart team (based on symptoms, documented ischemia, and viability). Both the native lesion and the venous graft lesion must be deemed suitable for PCI with a commercially available second generation DES. Informed consent must be obtained Exclusion Criteria: < 18 years of age Target vessel diameter < 2.5 mm CABG performed less than 1 year prior to inclusion Diameter of the graft > 5.5 mm Aneurysm formation in the bypass graft Heavy burden of thrombus in the bypass graft (>50% of the bypass graft lumen in ≥2 out of 3 of the proximal, middle or distal third of the bypass graft). STEMI at presentation NSTEMI patients with ongoing ischemia Cardiogenic shock Severe kidney disease defined as an eGFR < 30 ml/min. Pregnancy Estimated life expectancy < 3 year Contraindications to PCI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to either native vessel PCI or PCI of the venous bypass graft in a 1:1 fashion. Randomization will be performed using an interactive Web-based randomization system, Open Clinica
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Native Vessel PCI<br>All patients with a significant stenosis (>50% on coronary angiography) in a venous bypass graft discussed in the local heart team for revascularization will be screened for potential inclusion in the study. Percutaneous coronary intervention of the native vessel will be performed according to current standard. In case of a CTO lesion, the aforementioned hybrid approach will be applied.This approach uses several angiographic characteristics to guide strategical planning of the procedure, using four complementary techniques to cross a CTO: antegrade wire escalation, antegrade dissection reentry, retrograde wire escalation and retrograde dissection reentry. | Procedure: Percutaneous coronary intervention<br>* PCI of the bypass graft will be performed by current standards and at the discretion of the operator. Only commercially available second generation DES - XIENCE Sierra will be used. In case of a CTO lesion, the aforementioned hybrid approach will be applied.This approach uses several angiographic characteristics to guide strategical planning of the procedure, using 4 complementary techniques to cross a CTO: antegrade wire escalation, antegrade dissection reentry, retrograde wire escalation, retrograde dissection reentry. In case of PCI failure, a second attempt can be performed within 1 month. Patients will be hospitalized for a min. of 6-8 hours after PCI and receive DAPT prior to the procedure or triple therapy in case of indication for oral anticoagulation, their duration according to the current guidelines of the ESC for stable coronary disease or ACS.<br>|
| Other: Graft PCI<br>All patients with a significant stenosis (>50% on coronary angiography) in a venous bypass graft discussed in the local heart team for revascularization will be screened for potential inclusion in the study. Percutaneous coronary intervention of the bypass graft will be performed following current standards and at the discretion of the operating interventional cardiologist. Only commercially available second generation DES will be used in the treatment of bypass grafts. The second generation DES used in this study will be the XIENCE Sierra stent. The use of a filter-wire during the procedure will be left at the discretion of the operator. | Procedure: Percutaneous coronary intervention<br>* PCI of the bypass graft will be performed by current standards and at the discretion of the operator. Only commercially available second generation DES - XIENCE Sierra will be used. In case of a CTO lesion, the aforementioned hybrid approach will be applied.This approach uses several angiographic characteristics to guide strategical planning of the procedure, using 4 complementary techniques to cross a CTO: antegrade wire escalation, antegrade dissection reentry, retrograde wire escalation, retrograde dissection reentry. In case of PCI failure, a second attempt can be performed within 1 month. Patients will be hospitalized for a min. of 6-8 hours after PCI and receive DAPT prior to the procedure or triple therapy in case of indication for oral anticoagulation, their duration according to the current guidelines of the ESC for stable coronary disease or ACS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount and type of Major Adverse Cardiac Events | The total number and specification of major adverse cardiac events (all-cause mortality, non-fatal myocardial infarction, or clinically driven target lesion revascularization). | 3 year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount and type of Major Adverse Cardiac Events | The total number and specification of major adverse cardiac events (all-cause mortality, non-fatal myocardial infarction, or clinically driven target lesion revascularization). | 1 and 5 year follow-up | 
| Amount of patients that have passed away | Mortality score, all-cause mortality | 1, 3 and 5 year follow-up | 
| Number of non-fatal myocardial infarctions | Any non-fatal myocardial infarction noticed | 1, 3 and 5 year follow-up | 
| Number of clinically driven target lesion revascularizations | Any clinically driven target lesion revascularization noticed | 1, 3 and 5 year follow-up | 
| Number of target vessel revascularizations | Any target vessel revascularization noticed. | 1, 3 and 5 year follow-up | 
| Number of target vessel failure. | Any target vessel failure noticed | 1, 3 and 5 year follow-up | 
| Number of non-fatal myocardial infarctions. | Any non-fatal myocardial infarction noticed. | >48 hours after PCI | 
| Number of PCI-related myocardial infarctions. | Any PCI-related myocardial infarction noticed. | 1, 3 and 5 year follow-up | 
| Specific angiographic outcome | Any of the following outcomes: Late lumen loss In-stent binary restenosis (≥50%) In-stent re-occlusion Difference in in-stent diameter stenosis between index procedure at inclusion, and at 3-year follow-up | 3-year follow up | 
| Quality of life assessed by SAQ | The Seattle Angina Questionnaire is a self-assessment questionnaire where patients' physical limitations caused by angina are quantified, as well as the frequency of and changes in their symptoms, their satisfaction with treatment and how they perceive their Quality of Life. Each scale is transformed to a 0-100 scale. the higher the score, the better the patients functions/the higher the Quality of Life. | 1, 3 and 5 year follow-up | 
| Quality of life assessed by CCS | Canadian Cardiovascular Society (CCS) Grading Scale measures whether patient have angina pectoris complaints, and to what extent patients experienced this. It uses a scale of 1-4 where 1 means angina pectoris (chest pain) only occurs with streneous, rapid or prolonged exertion, and 4 means angina is present during little physical effort or even during rest. | 1, 3 and 5 year follow-up | 
| Quality of life assessed by RDS | Rose dyspnea scale questionnaire (RDS) measures dyspnea complaints, or shortness of breath. It consists of 4 questions about dysnpea complaints in the everyday life of patients. For every patient, a score is compiled of the highest limitation in daily life, resulting in a score of 0-4, where 0 means no dyspnea complaints and 4 means the patient has complaints during no or minimal physical effort. The scores from these questionnaires will be combined by summing the total scores. | 1, 3 and 5 year follow-up | 
| Composite score of quality of life | Composite of all quality of life questionnaires, where all outcomes are summed to provide a total score | 3-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dysfunctional venous bypass graft, Percutaneous Coronary Intervention, Second generation DES, CABG