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

The Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Heart Failure Systolic
• Intervention / Treatment: Procedure: Revascularization by PCI; Procedure: Revascularization by CABG

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 754
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephen Fremes, MD,MSc,FRCSC; Phone Number: 6073 416-480-6100; Email: stephen.fremes@sunnybrook.ca
• Study Contact Backup: Name: Reena Karkhanis, MBBS,DA,MSc; Phone Number: 6086 416-480-6100; Email: reena.karkhanis@sunnybrook.ca

Study Locations

• Austria
  • Vienna, Austria
    • Recruiting
    • Medical University of Vienna
    • Contact: Sigrid Sandner
    • Sub-Investigator: Alexander Niessner
    • Sub-Investigator: Eva Steinacher
    • Sub-Investigator: Alexander Geppert
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Recruiting
      • University of Calgary; Libin Cardiovascular Institute
      • Contact: Robert Miller
      • Sub-Investigator: Imtiaz Ali
      • Sub-Investigator: Bryan Har
      • Sub-Investigator: Jonathan Howlett
      • Sub-Investigator: Nowell Fine
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L3W7
      • Recruiting
      • Fraser Health; Royal Columbian Hospital
      • Contact: Daniel Wong
      • Sub-Investigator: Michael Diamant
      • Sub-Investigator: Albert Chan
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton General Hospital
      • Contact: Catherine Demers
      • Sub-Investigator: Sanjit Jolly
      • Sub-Investigator: Iqbal Jaffer
      • Sub-Investigator: Dominic Parry
      • Sub-Investigator: Nicholas Valettas
      • Sub-Investigator: Niloufar Ahmadbeigi
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Center, University Hospital
      • Contact: David Nagpal
      • Sub-Investigator: Michael Chu
      • Sub-Investigator: Pallav Garg
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Recruiting
      • Southlake Regional HC
      • Contact: Liane Porepa
      • Sub-Investigator: Christopher Overgard
      • Sub-Investigator: Charles Peniston
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Center
      • Contact: Stephen Fremes, MD,FRCS(C); Phone Number: 66073 1-416-480-6100
      • Sub-Investigator: Dennis Ko
      • Sub-Investigator: Stephanie Poon
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • Toronto General Hospital
      • Contact: Vivek Rao
      • Sub-Investigator: Michael McDonald
      • Sub-Investigator: Vlad Dzavik
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's
      • Contact: Akshay Bagai
      • Sub-Investigator: Michael Kutryk
      • Sub-Investigator: John Graham
      • Sub-Investigator: Sami Alnasser
      • Sub-Investigator: Neil Fam
      • Sub-Investigator: Subodh Verma
      • Sub-Investigator: Bobby Yanagawa
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
      • Contact: Emmanuel Moss
      • Sub-Investigator: Mark J Eisenberg
      • Sub-Investigator: Richard Sheppard
    • Montréal, Quebec, Canada, H1T 1C8
      • Recruiting
      • Montreal Heart Institute
      • Contact: Gilbert Gosselin; Phone Number: 3238 514-376-3330
      • Sub-Investigator: Jean-Lucien Rouleau
      • Sub-Investigator: Pierre-Emmanuel Noly
      • Sub-Investigator: Jean-Francois Tanguay
      • Sub-Investigator: Guillaume Maquis-Gravel
      • Sub-Investigator: Robert Avram
      • Sub-Investigator: Normand Racine
      • Sub-Investigator: Eileen O'Meara
      • Sub-Investigator: Anique Ducharme
      • Sub-Investigator: Nadia Bouabdallaoui
      • Sub-Investigator: Christine Henri
      • Sub-Investigator: Maxime Tremblay-Gravel
    • Montréal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hospital Sacre-Coeur
      • Contact: Erick Schampaert
      • Sub-Investigator: Frederic Poulin
      • Sub-Investigator: Hugues Jeanmart
    • Montréal, Quebec, Canada, , H2X OC1
      • Recruiting
      • Center Hospitalier Universitaire de Montreal
      • Contact: Samer Mansour
      • Sub-Investigator: Nicolas Noiseux
      • Sub-Investigator: Véronique Cyr
      • Sub-Investigator: Brian Potter
      • Sub-Investigator: Alexis Matteau
      • Sub-Investigator: Jessica Forcillo
      • Sub-Investigator: Jean-Bernard Masson
      • Sub-Investigator: Marc Jolicoeur
      • Sub-Investigator: Francois Gobeil
      • Sub-Investigator: Mounir Riahi
      • Sub-Investigator: Vu-Hung Quan
      • Sub-Investigator: Giovanni Romanelli
      • Sub-Investigator: Louis-Mathieu Stevens
    • Québec, Quebec, Canada, G1V 4G5
      • Recruiting
      • Institut de Cardiologie Quebec (QC) - Laval
      • Contact: Dimitri Kalavrouziotis
      • Sub-Investigator: Jean-Michel Paradis
      • Sub-Investigator: Mathieu Bernier
• China
  • Changchun
    • Jilin, Changchun, China, 130117
      • Recruiting
      • Jilin Heart Hospital
      • Contact: Massimo Lemma
      • Sub-Investigator: Francesco Lavarra
• Croatia
  • Zagreb
    • Sušak, Zagreb, Croatia, 10000
      • Recruiting
      • Clinical Hospital Dubrava
      • Contact: Igor Rudez
      • Sub-Investigator: Davor Baric
      • Sub-Investigator: Daniel Unic
      • Sub-Investigator: Josip Varvodic
      • Sub-Investigator: Marko Kusurin
      • Sub-Investigator: Sime Manola
      • Sub-Investigator: Nikola Pavlovic
      • Sub-Investigator: Mario Udovicic
• India
  • Tamil Nadu
    • Palayam, Tamil Nadu, India, 641037
      • Recruiting
      • G Kuppuswamy Naidu Memorial Hospital (GKNM)
      • Contact: Chandrasekar Padmanabhan
      • Sub-Investigator: Rajpal Abhaichand
      • Sub-Investigator: Shanmuga Sundaram
• Italy
  • RM
    • Roma, RM, Italy, 00149
      • Recruiting
      • European Hospital, Via Portuense
      • Contact: Ruggero De Paulis; Phone Number: 39 0665975224
      • Sub-Investigator: Luca Weltert
      • Sub-Investigator: Gianpiero Italiano
• Poland
  • Katowice, Poland
    • Recruiting
    • Medical University of Silesia
    • Sub-Investigator: Marcin Malinowski
    • Contact: Marek Deja
    • Sub-Investigator: Wojciech Wojakowski
    • Sub-Investigator: Paweł Gąsior
    • Sub-Investigator: Joanna Ciosek
    • Sub-Investigator: Marta Bujak
• Serbia
  • Belgrade, Serbia
    • Recruiting
    • Dedinje Cardiovascular Institute
    • Contact: Milan Milojevic
    • Sub-Investigator: Goran Loncar
    • Sub-Investigator: Petar Otasevic
    • Sub-Investigator: Slobodan Micovic
• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital del Vinalopó
    • Contact: Jose Albors Martin
    • Sub-Investigator: Edgardo Castillo
    • Sub-Investigator: Daniel Nuñez
    • Sub-Investigator: Beatriz Miralles
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Mauricio Villavicencio Theoduloz
      • Sub-Investigator: Trevor Simard
      • Sub-Investigator: Atta Behfar
      • Sub-Investigator: John Stulak
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: Rakesh Arora
      • Sub-Investigator: Yasir Abu-Omar
      • Sub-Investigator: Anene Ukaigwe
      • Sub-Investigator: Eiran Gorodeski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years;
2. LVEF ≤40% quantified by either echocardiography, SPECT ventriculography, or magnetic resonance within 2 months of randomization;
3. 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;
4. 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:

1. 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;
2. Recent (<4 weeks) ST-elevation MI;
3. Concomitant severe valvular disease or other condition such as left ventricular aneurysm requiring surgical repair or replacement;
4. Planned major concomitant surgical procedures (LAAO and AF ablation surgical procedures permitted);
5. Prior PCI within the past 12 months (to reduce restenosis events from prior PCIs contributing to the primary outcome);
6. Prior cardiac surgery;
7. Prohibitive bleeding risk mandating avoidance of dual antiplatelet therapy;
8. Circumstances likely to lead to poor treatment adherence;
9. Severe end-organ dysfunction (such as dialysis, liver failure, respiratory failure, cancer) that reduces life expectancy to less than 5 years;
10. Current pregnancy;
11. Patient not amenable to both CABG or PCI according to the Heart Team;
12. Takotsubo/Takotsubo Cardiomyopathy/Broken Heart Syndrome;
13. Failure to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Revascularization by PCI; 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; 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.
Experimental: Revascularization by CABG; 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; 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.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire-12	The scores range from 0-100 with higher scores indicating higher quality of life. The scores are classified as 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.	Through study completion with a median follow-up of 5 years.
Seattle Angina Questionnaire-7	It generates a summary score (scale 0-100, 100 = full health, 0 = worst health).	Through study completion with a median follow-up of 5 years.
Short Form 12 Questionnaire	Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	Through study completion with a median follow-up of 5 years.
EuroQol-5D (EQ-5D)	Each dimension in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). The EQ-5D index score is anchored at 1 (full health) and 0 (death).	Through study completion with a median follow-up of 5 years.
Montreal Cognitive Assessment (MoCA)	Scores on the MoCA range from 0-30; a score of 26 or above is considered normal with higher scores indicating higher cognitive function.	Through study completion with a median follow-up of 5 years.
Composite of severe stroke/ventilator dependance/new onset or worsening heart failure/ nursing home admission/ or new onset dialysis	It will be measured as a time to event outcome.	Reported at 1 and 5 years and as a cumulative incidence.
Composite of stroke, nursing home admission and 3 or more non-elective admissions per 12 months	It will be measured as a time to event outcome.	Reported at 1 and 5 years and as a cumulative incidence.
Length of stay outcomes	Length of stay of index ICU admission, Length of hospital stay of index admission. Days alive and out of hospital (DAOH).	Reported at 90 days, 1 year and 5 years - this is only for DAOH.
Cumulative costs	Cumulative costs will be collected over 4 years.	4 years.
Cost-effectiveness	Quality adjusted life years over four years based on EQ-5D at each follow-up time point and four-year cumulative costs.	4 years.

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Institutes of Health Research (CIHR); Weill Medical College of Cornell University
• Investigators: Principal Investigator: Stephen Fremes, MD,MSc,FRCSC, Sunnybrook Health Sciences Center, Toronto, Canada

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2023
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PCI; CABG; Left ventricular dysfunction; MACCE
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Failure; Coronary Artery Disease; Cardiomyopathies; Heart Failure, Systolic
• Other Study ID Numbers: v.1.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No