The Ideal Sequence of Hybrid Coronary Revascularization With Endoscopic Coronary Revascularization

Study Overview
=================
Brief Summary
-----------------
Hybrid coronary revascularization (HCR), a combination of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI), has emerged as an alternative treatment for multivessel coronary artery disease patients. However, the ideal sequence (PCI or CABG) is unclear. The overall aim of this study is to investigate the best sequence within hybrid coronary revascularization using endoscopic coronary bypass grafting (i.e., first CABG then PCI versus first PCI then CABG)

Detailed Description
-----------------
Hybrid coronary revascularization (HCR) is an emerging approach for multivessel coronary artery disease (MVD) which combines the excellent long-term outcomes of surgery with the early recovery and reduced short-term complications of percutaneous coronary intervention (PCI). However, the best sequence within hybrid coronary revascularization remains unclear. When CABG is performed first (standard HCR), incomplete revascularization can cause acute coronary events in the interim period. On the other hand, when PCI is performed first (reverse HCR), bleeding risks may be higher since CABG should be performed on uninterrupted dual anti-platelet therapy (DAPT). The use of minimally invasive surgery techniques is associated with reduced bleeding because of the less surgical trauma and may offer the opportunity to perform reverse HCR due to the possibility to reduce the risk of bleeding. The overall aim of this study is to investigate the best sequence within hybrid coronary revascularization using endoscopic coronary bypass grafting (i.e., first CABG then PCI versus first PCI then CABG, figure 1)

Official Title
-----------------
A Randomized Controlled Trial to Investigate the Ideal Sequence of Hybrid Coronary Revascularization With Endoscopic Coronary Revascularization

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Procedure: Standard hybrid coronary revascularization
* Procedure: Reverse hybrid coronary revascularization


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Multivessel coronary disease, defined as ≥ 50% diameter stenosis by visual estimation in 2 or more of the three major epicardial vessels or major side branches, with at least one or more one stenosis amenable to revascularization with PCI, if the patient cannot be full revascularized by surgery for a specific reason as determined by the Heart Team. Patients with a non-dominant right coronary artery may be included if the left anterior descending artery (LAD) and left circumflex have ≥50% stenosis. Age 18-85 Willing and able to provide informed, written consent Exclusion Criteria: Requirement for other cardiac or non-cardiac surgical procedures (e.g., valve replacement, carotid revascularization) Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support at the time of randomisation Left main coronary artery disease Contraindication for dual antiplatelet therapy ST-Elevation Myocardial Infarction (STEMI) Previous cardiac surgery Participation in other interventional clinical trials Recent coronary intervention (PCI) Ongoing high risk non-ST-segment elevation acute coronary syndrome (ACS) Life expectancy < 1 year Active bleeding more or equal to BARC 2 at time of randomisation Requiring renal replacement therapy Undergoing evaluation for organ transplantation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reverse hybrid coronary revascularization (HCR)<br>Patients will undergo reverse hybrid coronary revascularization. Moreover, quality of life is assessed at baseline, 14 days, 30 days, 90 days, 6 months and 1 year. | Procedure: Reverse hybrid coronary revascularization<br>* Patients will receive a percutaneous coronary intervention (PCI) within four weeks after the diagnostic coronarography. Furthermore, they will undergo the endoscopic coronary artery bypass grafting (endo-CABG) within four weeks after the PCI.<br>|
| Active Comparator: Standard hybrid coronary revascularization (HCR)<br>Patients will undergo standard hybrid coronary revascularization. Moreover, quality of life is assessed at baseline, 14 days, 30 days, 90 days, 6 months and 1 year. | Procedure: Standard hybrid coronary revascularization<br>* Patients will undergo endoscopic coronary artery bypass grafting (endo-CABG) within four weeks after the diagnostic coronarography. Furthermore, they will receive a percutaneous coronary intervention (PCI) within four weeks after the endo-CABG.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day net adverse clinical event (NACE) | NACE consists of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding unrelated to CABG (Bleeding Academic Research Consortium (BARC) type 3 and 5) MACCE consists of: Death from any cause Myocardial infarction Stroke Target lesion revascularisation | From the first procedure until 30 days after the second procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary outcome: 30-day major adverse cardiac and cerebrovascular events (MACCE) | MACCE consists of: Death from any cause Myocardial infarction Stroke Target lesion revascularisation | From the first procedure until 30 days after the second procedure | 
| Key secondary outcome: 30-day major or clinically relevant non-major bleeding (BARC type 2, 3, 4, 5) | Major or clinically relevant non-major bleeding is assessed using BARC type 2, 3, 4, and 5. | From the first procedure until 30 days after the second procedure | 
| Key secondary outcome: One-year net adverse clinical event (NACE) | NACE consists of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding unrelated to CABG (Bleeding Academic Research Consortium (BARC) type 3 and 5) MACCE consists of: Death from any cause Myocardial infarction Stroke Target lesion revascularisation | From the first procedure until one year after the second procedure | 
| Key secondary outcome: one-year major adverse cardiac and cerebrovascular events (MACCE) | MACCE consists of: Death from any cause Myocardial infarction Stroke Target lesion revascularisation | From the first procedure until one year after the second procedure | 
| Key secondary outcome: One-year major or clinically relevant non-major bleeding (BARC type 2, 3, 4, 5) | Major or clinically relevant non-major bleeding is assessed using BARC type 2, 3, 4, and 5. | From the first procedure until one year after the second procedure | 
| Mortality | Both all-cause mortality as the subdivision in cardiovascular death, noncardiovascular death and undetermined cause of death are examined. | From the first procedure until one year after the second procedure | 
| Myocardial infarction | Mycardial infarction is subdivided into: Periprocedural Spontaneous | From the first procedure until one year after the second procedure | 
| Stent thrombosis | Stent thrombosis is subdivided into: Definite stent thrombosis Probable stent thrombosis Possible stent thrombosis | From the first procedure until one year after the second procedure | 
| Stroke | Stroke is subdivided into: Ischemic stroke Hemorrhagic stroke Non-specified stroke | From the first procedure until one year after the second procedure | 
| Revascularization | Revascularization is subdivided into: Target lesion revascularization (TLR) Target vessel revascularization (TVR) | From the first procedure until one year after the second procedure | 
| Graft failure | Graft failure describes total graft occlusion that prevents blood flow through the graft to the revascularized part of the heart. | From the first procedure until one year after the second procedure | 
| Bleeding | Bleeding is assessed using the Bleeding Academic Research Consortium (BARC) classification, Thrombolysis In Myocardial Infarction (TIMI) bleeding classification and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO). classification BARC is subdivided into type zero (no bleeding) until five (probable/definite fatal bleeding), while the TIMI classification is divided into minimal, minor, and major. Gusto is subdivided into mild, moderate, and severe. | From the first procedure until one year after the second procedure | 
| Quality of Life (QoL) using the Short-form 36 (SF-36) questionnaire | QoL will be questioned with the Short-form 36 (SF-36) questionnaire.SF-36 scores range from 0 (worst) to 100 (best). | 14, 30, 90, 180 and 365 days after the second procedure | 
| Quality of Life (QoL) using the Euro Quality of Life 5 dimensions (EQ-5D) questionnaire | The Euro Quality of Life 5 dimensions (EQ-5D) questionnaire will be used to assess Quality of Life. Questions of the descriptive system are scored from one (no problem to perform activity) to five (severe problem/unable to perform activity). The scores are combined in order to calculate an index value (ranging from 0-1) that reflects the health state with one being the best health state. Moreover, the visual analogue scale ranges from 0 to 100 with 0 representing the worst health state and 100 the best health state. | 14, 30, 90, 180 and 365 days after the second procedure | 
| Quality of Life (QoL) using the Seattle Angina Questionnaire short-form (SAQ-7) | QoL will be questioned with the Seattle Angina Questionnaire short-form (SAQ-7). The overall summary score ranges from 0 to 100 where higher ratings indicate a better health state. | 14, 30, 90, 180 and 365 days after the second procedure | 
| Quality of Life (QoL) using the Rose Dyspnea Scale (RDS) | The Rose Dyspnea Scale (RDS) will be used to assess Quality of Life. RDS is scored between zero and four. Zero corresponds to no dyspnea with activity and four to dyspnea that severly limits activity. | 14, 30, 90, 180 and 365 days after the second procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hybrid coronary revascularization, Coronary revascularization