The Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy Trial

Study Overview
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Brief Summary
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The Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy (STICH3C) trial is a prospective, unblinded, international multi-center randomized trial of 754 subjects enrolled in approximately 45 centers comparing revascularization by percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG) in patients with multivessel/left main (LM) coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). The primary objective is to determine whether CABG compared to PCI is associated with a reduction in all-cause death, stroke, spontaneous myocardial infarction (MI), urgent repeat revascularization (RR), or heart failure (HF) readmission over a median follow-up of 5 years in patients with multivessel/LM CAD and ischemic left ventricular dysfunction (iLVSD). Eligible patients are considered by the local Heart Team appropriate and amenable for non-emergent revascularization by both modes of revascularization. The secondary objectives are to describe the early risks of both procedures, and a comprehensive set of patient-reported outcomes longitudinally.

Detailed Description
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The evidence comparing PCI and CABG with medical therapy in patients with iLVSD has been the subject of multiple systematic reviews/meta-analyses of observational studies with inconsistent results. There is a current lack of evidence from properly powered randomized trials comparing contemporary state-of-the-art PCI vs. CABG to guide the clinical management in the vulnerable population of patients with iLVSD. Understanding the relative impact of both revascularization strategies on clinical outcomes in this prevalent population would have important clinical implications. The overarching aim of the STICH3C trial is to compare the clinical efficacy and safety of contemporary PCI and CABG to treat patients with multivessel/left main (LM) CAD and iLVSD. Participants will be allocated in a 1:1 ratio to either study arm using permuted block randomization stratified for study center and acute coronary syndrome (ACS) presentation through a centrally controlled, automated, web system. Eligible patients who provide informed consent can be enrolled. It is expected that initial revascularization will take place within 2 weeks of randomization. Staged PCI is expected to take place within 90 days of randomization. The recruitment will occur over 3 years, with a total study duration of 7 years, and a median duration of follow-up of 5 years.

Official Title
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The Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy (STICH3C) Trial

Conditions
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Coronary Artery Disease, Heart Failure Systolic

Intervention / Treatment
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* Procedure: Revascularization by PCI
* Procedure: Revascularization by CABG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years; LVEF ≤40% quantified by either echocardiography, SPECT ventriculography, or magnetic resonance within 2 months of randomization; Prognostically important multivessel CAD (triple vessel CAD or double vessel disease including the left anterior descending (LAD) or LM). Significant coronary stenosis is defined as ≥ 70% based on coronary angiography, and/or fractional flow reserve (FFR) ≤0.80 or instantaneous wave-free ratio (iFR) ≤0.89. For LM disease, significant coronary stenosis is defined as >50% based on coronary angiography, intravascular ultrasound (IVUS) minimal luminal area (MLA) ≤6.0 mm2 (<4.5 mm2 Asian descent), or equivalent optical coherence tomography (OCT) measurements; The institutional Heart Team agrees that guideline-directed medical therapy (GDMT) has been initiated for ≥1 month in prevalent and newly diagnosed cases. In patients hospitalized with newly diagnosed iLVSD (with or without acute coronary syndrome (ACS)) requiring revascularization before discharge, GDMT needs to be initiated, when possible in-hospital before randomization, with the expectation that it will be titrated to maximally tolerated doses after revascularization. Exclusion Criteria: Decompensated HF requiring inotropic/adrenergic support, invasive or non-invasive ventilation or intra-aortic balloon pump/ventricular assist device therapy less than 48 hours prior to randomization; Recent (<4 weeks) ST-elevation MI; Concomitant severe valvular disease or other condition such as left ventricular aneurysm requiring surgical repair or replacement; Planned major concomitant surgical procedures (LAAO and AF ablation surgical procedures permitted); Prior PCI within the past 12 months (to reduce restenosis events from prior PCIs contributing to the primary outcome); Prior cardiac surgery; Prohibitive bleeding risk mandating avoidance of dual antiplatelet therapy; Circumstances likely to lead to poor treatment adherence; Severe end-organ dysfunction (such as dialysis, liver failure, respiratory failure, cancer) that reduces life expectancy to less than 5 years; Current pregnancy; Patient not amenable to both CABG or PCI according to the Heart Team; Takotsubo/Takotsubo Cardiomyopathy/Broken Heart Syndrome; Failure to provide informed consent.

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: The STICH3C trial is a prospective, unblinded, international multi-center randomized trial of comparing revascularization by PCI vs. CABG in patients with multivessel/LM CAD and reduced LVEF.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revascularization by PCI<br>Revascularization will be attempted on/for significant lesions in major coronary vessels/side branches as planned by the local Heart Team, with the general recommendation of stenotic/occluded vessels with diameter >2.0 mm for PCI. The Heart Team consists of a minimum of one heart failure cardiologist, one interventional cardiologist and one cardiac surgeon. | Procedure: Revascularization by PCI<br>* Contemporary, State-of-the-art PCI techniques will be encouraged in STICH3C, based on the most recent evidence and clinical practice guidelines recommendations. The best practices to be followed include the use of physiological and intravascular guidance, new-generation drug-eluting stents or scaffolds, rotational or orbital atherectomy for extensive calcifications, recommended bifurcation techniques, chronic total occlusion for viable segments by experienced operators, and trans-radial access.Planned temporary ventricular support is permitted by experienced operators when deemed indicated.<br>|
| Experimental: Revascularization by CABG<br>Revascularization will be attempted on/for significant lesions in major coronary vessels/side branches as planned by the local Heart Team, with the general recommendation of stenotic/occluded vessels with diameter >1.5 mm for CABG. The Heart Team consists of a minimum of one heart failure cardiologist, one interventional cardiologist and one cardiac surgeon | Procedure: Revascularization by CABG<br>* The surgical revascularization strategy will be tailored according to the individual patient's coronary anatomy, left ventricular remodeling, aortic atherosclerosis, co-morbidities, local expertise, and surgical judgement. An internal thoracic artery will be used to graft the left anterior descending in all cases. Multi-arterial grafting may be considered in patients without significant co-morbidities and with expected limited vasopressor use, or in patients without saphenous conduits. Choice of on- vs. off-pump surgery is influenced by LV size, associated valvular disease, and aortic atherosclerosis, as well as surgeon experience, but on-pump surgery is recommended routinely. The use of adjunctive intra-aortic balloon support or other cardiac support is not routinely recommended in stable patients; the intra-aortic balloon support is the first line mechanical support.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary outcome is a Composite of all-cause mortality, stroke, spontaneous myocardial infarction, urgent repeat revascularization or heart failure readmission. | Time to event outcome measured as the time from randomization to the occurence of the first event. | Median follow-up of 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Death will be reported at 30 days. Death over the entire duration of study will be reported as a time to event outcome. Death will be adjudicated as cardiovascular, non-cardiovascular and unknown. | At 30 days , 90 days and through study completion with a median follow-up of 5 years. | 
| Myocardial Infarction (MI) | Periprocedural/perioperative MI is defined as <48 hours from revascularization. Spontaneous MI is defined as > or = 48 hours post revascularization | At 30 days and through study completion with a median follow-up of 5 years. | 
| Number of participants with Stroke | Strokes will be classified as ischemic, hemorrhagic or uncertain. | At 30 days , 90 days and through study completion with a median follow-up of 5 years. | 
| Repeat Revascularization (RR) | Only urgent clinically driven unplanned repeat revascularizations by either PCI or CABG count towards primary ouctome. RR will be classified according to type (CABG vs. PCI), by location (target vessel vs. target lesion vs. graft vs. other), and whether clinically vs. non-clinically driven. Stent thrombosis (ARC defined) and graft thrombosis/ occlusion will be reported. | At 30 days , 90 days and through study completion with a median follow-up of 5 years. | 
| Hospitalizations | Hospitalizations will be defined as cardiac or non-cardiac. Hospitalizations will be reported as the number of participants with hospitalizations and as a count. | Through study completion with a median follow-up of 5 years. | 
| Composite of death/stroke/spontaneous MI | Measured as a time-to-event. | Through study completion with a median follow-up of 5 years. | 
| Composite of death/stroke/spontaneous MI/RR | Measured as a time-to-event. | Through study completion with a median follow-up of 5 years. | 
| Composite of death or cardiac hospitalization | Measured as a time-to-event. | Through study completion with a median follow-up of 5 years. | 
| Coronary composite endpoint | Coronary heart disease death, non-fatal MI, and coronary revascularization procedure. Measured as time-to-event outcome. | Through study completion with a median follow-up of 5 years. | 
| Heart Failure endpoint | Heart Failure Event (composite of heart failure death, heart failure hospitalization or revascularization for HF). Measured as time-to-event outcome. | Through study completion with a median follow-up of 5 years. | 
| Hierarchal Heart Failure outcome | The key hierarchal outcome of time to death and frequency of HF rehospitalizations will be tested using a win ratio | Through study completion with a median follow-up of 5 years. | 
| Number of participants with advanced Heart failure therapies | This includes - ICD/CRT implantation,Mitral valve repair (transcatheter/surgical),Ventricular Assist Device and Heart Transplant | Through study completion with a median follow-up of 5 years. | 
| Major Adverse Events | These will be reported as the composite and individually: new renal replacement therapy, major bleeding (Bleeding Academic Research Consortium (BARC) 3-5), major vascular complication (according to VARC-2 criteria), unplanned RR, other reoperation, surgical site complication, intubation >48 hours, cardiac arrest, advanced cardiac life support, stroke and death. | Results will be reported at 30 days and 90 days after index procedure (and 30 days after any planned staged PCI, allowed up to 90 days after randomization) as cardiac surgical hospitalizations maybe prolonged. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left ventricular dysfunction, CABG, PCI, MACCE