Hybrid Coronary Revascularization Trial
Hybrid Coronary Revascularization Trial
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.
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 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.
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

 -  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.