Clinical trial NCT03089398: Hybrid Coronary Revascularization Trial
Official title: Randomized Trial Of Hybrid Coronary Revascularization Versus Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Hybrid Coronary Revascularization
Coronary Artery Bypass Grafting
Percutaneous Coronary Intervention
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-03-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a prospective, multi-center randomized comparative effectiveness trial of HCR compared to multi-vessel PCI with metallic DES in patients with multi-vessel CAD involving the LAD or LM territories.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to learn which treatment option is better for patients who have multi-vessel coronary artery disease (blockages in more than one vessel supplying blood to the heart muscle). The treatment options this study will compare are: (1) Hybrid Coronary Revascularization \[HCR\] (a combination of surgery and catheter procedures to open up clogged heart arteries) and (2) Percutaneous Coronary Intervention \[PCI\] (catheter procedures alone to open up clogged heart arteries). There are no new or "experimental" procedures being tested in this study: both HCR and PCI are well-established procedures and are regularly performed in patients who have coronary artery disease. But, the FDA has not approved the drug-eluting stents used in PCI for all types of coronary artery disease. We have received an Investigational Device Exemption from the FDA to use the drug-eluting stents in this trial in the same way that they are used in clinical practice. The study being proposed here will use rigorous scientific methods and should result in a very high level of certainty about which procedure is best for patients with coronary artery disease.

Detailed description: The increasing prevalence of coronary artery disease (CAD), advances in coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and concomitant medical therapy, and the costs of revascularization have resulted in rising interest regarding the appropriate indications and alternatives for coronary revascularization.

Hybrid coronary revascularization is the intended combination of CABG and PCI. The HCR strategy combines grafting of the left anterior descending artery (LAD) coronary artery using the left internal mammary artery (LIMA) and PCI of non-LAD coronary stenoses. Essentially, stents are substituted for saphenous vein grafts (SVG) for non-LAD lesions, and the surgical LIMA to LAD bypass is performed, ideally through a limited access, minimally traumatic approach.

Unfortunately, the published data to date on HCR must be considered limited and hypothesis generating. Clinicians, payers, and patients are interested in the specific benefits of revascularization alternatives. HCR as a scientifically validated approach would have a major healthcare impact. The ability to deliver a new therapy for CAD that provides durability, but without the obligatory trauma and prolonged recovery time characteristic of conventional CABG would be a major advance in the field of cardiovascular medicine. The NHLBI-funded Hybrid Observational Study demonstrated that equipoise exists between the two coronary revascularization paradigms; however, a rigorously designed randomized clinical trial is now needed to provide sufficient evidence to guide clinical decision making for this important patient population.

This trial is a prospective, multi-center randomized comparative effectiveness trial of HCR compared to multi-vessel PCI in patients with multi-vessel CAD involving the LAD or left main (LM) territories. The trial is designed as a "large, simple" trial, and some baseline, procedure-related and short-term outcomes data collection will be extracted from existing registry data (Society of Thoracic Surgeons \[STS\] Data Registry). The overall objective of this trial is to evaluate the effectiveness and safety of Hybrid Coronary Revascularization (HCR) compared to multi-vessel PCI with drug-eluting stents (DES) in patients with multi-vessel coronary artery disease involving the Left Main and/or Left Anterior Descending arteries.

The primary objective the trial is to determine whether hybrid coronary revascularization is associated with a reduction in Major Adverse Cardiac and Cerebrovascular Events (MACCE) compared to PCI with DES.

The secondary objectives are to determine the impact of HCR compared to PCI on health status and quality of life.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation (US sites)
* Age ≥ 18 years
* Clinical indication for coronary revascularization
* Coronary anatomy requiring revascularization as follows(2)

  * Multivessel CAD involving the LAD (proximal or mid) and/or LM (ostial, mid-shaft or distal) with at least 1 other epicardial coronary artery requiring treatment (LCX or RCA), OR
  * Single vessel disease involving the LAD and a major diagonal, with both requiring independent revascularization with at least one stent if randomized to HCR and stents for both the LAD and diagonal if randomized to multivessel PCI Note: If the patient qualifies based only on a LM lesion, then there must be involvement of the distal bifurcation (Medina 1,1,1) intended for treatment with a 2-stent approach (separate stents into the LAD and LCX) if randomized to PCI. However, if the patient also has non-LM disease in the RCA and/or non-ostial LAD and/or non-ostial LCX that requires separate treatment, any LM lesion is a valid criterion for enrollment, whether LM ostial, shaft or distal bifurcation disease, and any strategy of treating the LM may be employed, including not treating the ostial LCX, a provisional approach or a planned 2-stent strategy as appropriate. Similarly, if the patient qualifies based only on LAD-Dg disease, whether a bifurcation lesion or separate lesions in the LAD and Dg, without RCA or LCX disease, then both the LAD and Dg must be true lesions intended for stents (planned 2-stent approach). However, if the patient has LAD-Dg disease and a lesion in the RCA or LCX that also requires treatment, the LAD-Dg disease can then be treated in any fashion (2-stents, a provisional approach, or the Dg not even dilated if it is small), according to operator preference
* Suitable candidate for both PCI with metallic DES and HCR as determined by clinical assessment and angiogram review by an interventional cardiologist and a cardiac surgeon at the enrolling clinical site
* Ability to tolerate and no plans to interrupt dual anti-platelet therapy for ≥ 6 months if presentation with stable CAD, or ≥ 12 months if presentation with biomarker positive acute coronary syndrome (ACS)
* Willing to comply with all protocol required follow-up

Exclusion Criteria:

* Previous cardiac surgery of any kind, including CABG
* Previous thoracic surgery involving the left pleural space
* Previous LM or LAD stent (a) with evidence of in-stent restenosis or (b) within 1 cm of a qualifying lesion
* Previous PCI of the LM and/or LAD within 12 months prior to randomization
* PCI with bare metal stent (BMS) within 12 months prior to randomization
* Any complication or unsuccessful revascularization with PCI within 30 days prior to randomization.

Note: A patient may be considered eligible for enrollment if PCI with DES in non-LM and non-LAD territory was performed within 30 days prior to randomization, as long as revascularization was successful and uncomplicated, or has been performed more than 30 days prior even if unsuccessful or complicated

* Planned treatment with bioresorbable vascular scaffold(s) after randomization
* Total occlusion (TIMI 0 or 1 flow) of the LM, LAD or LCX.
* Cardiogenic shock at time of screening
* STEMI within 72 hours prior to randomization
* Need for concomitant vascular or other cardiac surgery during the index hospitalization (including, but not limited to, valve surgery, aortic resection, left ventricular aneurysmectomy, and carotid endarterectomy or stenting)
* Indication for chronic oral anticoagulation therapy at the time of randomization
* Any prior lung resection
* End-Stage Renal Disease (ESRD) on dialysis
* Patients who could not be switched from prasugrel or ticagrelor to clopidogrel, should that be needed prior to a CABG, during reverse HCR
* Extra-cardiac illness that is expected to limit survival to less than 5 years
* Allergy or hypersensitivity to any of the study drugs or devices used in the trial
* Therapy with an investigational drug, device or biologic within 1 year prior to randomization, or plan to enroll patient in additional investigational study during participation in this trial
* Unable to give informed consent or potential for noncompliance with the study protocol in the judgment of the investigator
* Pregnant at time of screening or unwilling to use effective birth control measures while dual antiplatelet therapy is required.

Primary outcomes:
measure: Major Adverse Coronary and Cerebrovascular Events (MACCE)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Hemoglobin Levels
timeFrame: Up to 90 days post-randomization
measure: Creatinine Levels
timeFrame: Up to 90 days post-randomization
measure: CK-MB Levels (ng/dL)
timeFrame: Up to 90 days post-randomization
measure: CK-MB Levels (IU/L)
timeFrame: Up to 90 days post-randomization
measure: Troponin Levels
timeFrame: Up to 90 days post-randomization
measure: Number of Participants Requiring Medications
timeFrame: 24 Hours Prior to, During, and Within 24 Hours of the Procedure
measure: Number of Participants Requiring Transfusion
timeFrame: Up to 90 days post-randomization
measure: Length of Stay
timeFrame: Up to 90 days post-randomization
measure: Discharge Disposition
timeFrame: Up to 90 days post-randomization
measure: Cost-Effectiveness
timeFrame: Up to 24 months
measure: Feasibility of Incorporating Registry Data in a Randomized Clinical Trial
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Fort Myers
country: United States
facility: HealthPark Lee Memorial Health Systems
state: Florida
city: Orlando
country: United States
facility: Orlando Health Heart Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: College Park
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: Universty of Minnesota
state: Minnesota
city: Camden
country: United States
facility: Our Lady of Lourdes Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore - Einstein
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center/Gates Vascular Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Syracuse
country: United States
facility: St. Joseph's Hospital Health Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Raleigh
country: United States
facility: WakeMed Health and Hospitals
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Harrisburg
country: United States
facility: Pinnacle Health Cardiovascular System
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Healthcare Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: The Reading Health System
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Research Institute at The Heart Hospital Baylor Plano
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Centre Intégré Universitaire/Sacre Coeur
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Emilia Bagiella, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ichan School of Medicine at Mount Sinai
name: Alan Moskowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: John Puskas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Gregg Stone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ganyukov VI, Kochergin NA, Shilov AA, Tarasov RS, Skupien J, Kozyrin KA, Barbarash OL, Musialek P. Randomized Clinical Trial of Surgical Versus Percutaneous Versus Hybrid Multivessel Coronary Revascularization: 3 Years' Follow-Up. JACC Cardiovasc Interv. 2021 May 24;14(10):1163-1165. doi: 10.1016/j.jcin.2021.02.037. No abstract available.