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

Coronary Artery Disease Clinical Trial

Official title:

The Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05427370
• Other study ID #: v.1.4; 06/Jul/2023
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2023
• Est. completion date: December 2029

Study information

• Verified date: June 2024
• Source: Sunnybrook Health Sciences Centre
• Contact: Stephen Fremes, MD,MSc,FRCSC
• Phone: 416-480-6100
• Email: stephen.fremes[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 754
• Est. completion date: December 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Coronary Artery Disease
• Heart Failure Systolic
• Heart Failure, Systolic

Intervention

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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Brazil	Institute of Cardiology	Porto Alegre
Canada	University of Calgary; Libin Cardiovascular Institute	Calgary	Alberta
Canada	Queen Elizabeth II Hospital	Halifax	Nova Scotia
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences Center, University Hospital	London	Ontario
Canada	Center Hospitalier Universitaire de Montreal	Montréal	Quebec
Canada	Hospital Sacre-Coeur	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	Fraser Health; Royal Columbian Hospital	New Westminster	British Columbia
Canada	Southlake Regional HC	Newmarket	Ontario
Canada	Institut de Cardiologie Quebec (QC) - Laval	Québec	Quebec
Canada	St. Michael's	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
China	Jilin Heart Hospital	Jilin	Changchun
Croatia	Clinical Hospital Dubrava	Sušak	Zagreb
India	G Kuppuswamy Naidu Memorial Hospital (GKNM)	Palayam	Tamil Nadu
Italy	European Hospital, Via Portuense	Roma	RM
Poland	Medical University of Silesia	Katowice
Serbia	Dedinje Cardiovascular Institute	Belgrade
Spain	Hospital del Vinalopó	Alicante
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	UofL Health, Inc	Louisville	Kentucky
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Canadian Institutes of Health Research (CIHR), Weill Medical College of Cornell University

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Canada,  China,  Croatia,  India,  Italy,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	Cumulative costs	Cumulative costs will be collected over 4 years.	4 years.
Other	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Composite of death/stroke/spontaneous MI	Measured as a time-to-event.	Through study completion with a median follow-up of 5 years.
Secondary	Composite of death/stroke/spontaneous MI/RR	Measured as a time-to-event.	Through study completion with a median follow-up of 5 years.
Secondary	Composite of death or cardiac hospitalization	Measured as a time-to-event.	Through study completion with a median follow-up of 5 years.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.