Hybrid Revascularization Observational Study

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT01121263
• Collaborator: International Center for Health Outcomes and Innovation Research (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 298
• Locations: 11
• Duration (Months): 39
• Patients Per Site: 27.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of the study is to get a better understanding of patients who have multi-vessel coronary artery disease (blockages in more than one vessel bringing blood to the heart) and have either Hybrid Coronary Revascularization [HCR] (combination of surgery and catheter procedures to open up clogged heart arteries) or Percutaneous Coronary Intervention [PCI] (catheter procedures to open up clogged heart arteries). Participation in the study will last up to 21 months after a patient's heart procedure(s). The study collects information about the medical care patients receive during their planned procedure(s) and how well they do following the procedure(s). No new testing or procedures will be done. Patients will receive only the tests or procedures their doctor already has planned for them. The information collected should help to plan the design of a pivotal comparative effectiveness study of hybrid revascularization.

Condition or Disease	Intervention/Treatment	Phase
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 for coronary revascularization. For patients with 3-vessel disease, revascularization by CABG has recently been rated as appropriate while revascularization by PCI has been rated uncertain. Ideally, physicians would like to offer their multi-vessel CAD patients what they truly seek: a solution which provides a safe, minimally invasive treatment that does not compromise long term durability and survival. Integrating the positive features of both PCI and CABG has been the fundamental rationale of "hybrid" coronary revascularization.

Hybrid Coronary Revascularization (HCR) (the intended combination of CABG and PCI) 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. Candidates in whom HCR would be particularly advantageous would be several subgroups of CAD patients that are increasing in numbers: the elderly, patients with a high predicted risk of mortality and/or morbidity for CABG, deconditioned patients or patients with significant disabilities and patients in whom treatment durability is important, but a significantly invasive approach is not an option. Moreover, HCR is likely to bridge the divide in treatment philosophies and approaches that exist between cardiologists and cardiac surgeons. Collaboration rather than competition between these specialties will ultimately benefit patients, hospitals, payers and healthcare providers. The Hybrid Revascularization Observational Study is a multi-center observational study planning grant which will explore target populations for Hybrid Coronary Revascularization (HCR), their outcomes, and variations in specific ways these patients are managed, in order to inform the design of a pivotal comparative effectiveness trial of this emerging therapeutic strategy.

Given the observational nature of the study, the HCR and PCI groups' baseline characteristics and event rates are not directly comparable; rather, the results were intended to inform the design of a larger, randomized pivotal trial. The study was designed in two phases: Cohort 1, which captured demographic, angiographic, and practice patterns data for 6,669 consecutively screened patients; and Cohort 2 which captured demographic, angiographic, practice patterns, and outcome data for 298 patients who underwent either HCR or PCI with DES (90 of whom were also part of Cohort 1).

Study Design

• Study Type: Observational
• Actual Enrollment: 298 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Hybrid Revascularization Observational Study
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Angiogram Review Group All consecutive and consenting patients undergoing diagnostic cardiac catheterization in a 3 month period
Therapeutic Intervention Group Cohort 2 Therapeutic Intervention Group - HCR Patients (including those from the angiogram review group) who undergo Hybrid coronary revascularization (HCR) with minimally invasive LIMA-LAD CABG, OR Cohort 2 Therapeutic Intervention Group - PCI Patients (including those from the angiogram review group) who meet the proposed anatomic and clinical eligibility criteria and undergo multivessel Percutaneous Coronary Intervention with Drug Eluting Stents

Outcome Measures

Primary Outcome Measures

1. Major Adverse Cardiac and Cerebrovascular Event (MACCE) [Month 12]

   For the purposes of this study MACCE is defined as a non-weighted composite score comprised of the following components: Death Stroke Myocardial Infarction Repeat Revascularization

Secondary Outcome Measures

1. Major Adverse Cardiac and Cerebrovascular Event (MACCE) [Occurence of MACCE through the end of study up to two years]

   For the purposes of this study MACCE is defined as a non-weighted composite score comprised of the following components: Death Stroke Myocardial infarction Repeat revascularization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

The following criteria apply to Cohort 2 PCI patients only:

Inclusion Criteria:

• Signed informed consent, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documents

• Age 18 years or older

• Clinical indication for revascularization

• LAD and at least one additional vessel coronary disease (> 70% stenosis) confirmed by angiogram

• Clinical characteristics and multi-vessel disease amenable to both PCI with DES and Hybrid as adjudicated by one interventional cardiologist and one cardiac surgeon

• Ability to tolerate and no plans to interrupt double platelet therapy for ≥ 12 months

• Ability to tolerate to single lung ventilation in the judgment of the investigator

• Willing to comply with all protocol required follow-up

Exclusion Criteria:

• Previous coronary stent within:

• 1 month prior to enrollment for bare metal stent (BMS) or

• 6 months prior to enrollment for DES

• Evidence of in stent restenosis of a DES or BMS

• Previous cardiac surgery of any kind

• Chronic total occlusion (CTO) in LAD or ≥ 2 CTOs in major coronary territories that are considered targets for revascularization

• Left main disease ≥ 50% stenosis

• Presence of fresh coronary thrombus

• Need for concomitant vascular or other cardiac surgery during the index hospitalization (including, but not limited to, valve surgery, aortic resection, left ventricular aneurysm, carotid endarterectomy or stenting, etc)

• Previous STEMI within 30 days prior to randomization

• Previous stroke within 6 months prior to randomization

• Previous thoracic surgery involving the left pleural space

• Acute decompensated heart failure within 30 days prior to randomization

• Ejection fraction < 30%

• Creatinine clearance ≤ 50 ml/min within 24 hours prior to randomization

• Hemodynamic instability at time of screening

• Body mass index > 40

• Extra-cardiac illness that is expected to limit survival to less than 3 years

• Participation or planned participation in another investigational intervention study within 60 days prior to randomization

• Unable to give informed consent or potential for noncompliance with the study protocol due to psychiatric illness, organic brain disease, dementia, current alcohol abuse, mental retardation, language barrier, or geographical inaccessibility;

• Pregnancy at time of screening or intention to become pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30308
2	University of Maryland	Baltimore	Maryland	United States	21201
3	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
4	Montefiore Medical Center	Bronx	New York	United States	10461
5	Columbia University Medical Center	New York	New York	United States	10032
6	Duke University Medical Center	Durham	North Carolina	United States	27710
7	Ohio State University	Columbus	Ohio	United States	43210
8	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
9	Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
10	Vanderbilt University	Nashville	Tennessee	United States	37232
11	University of Virginia Health Systems	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai
• International Center for Health Outcomes and Innovation Research
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: John Puskas, MD, MSc, FACS, FACC, Emory University
• Principal Investigator: Deborah Ascheim, MD, Icahn School of Medicine at Mount Sinai (Data Coordinating Center)
• Principal Investigator: Joseph J DeRose, MD, FACS, Montefiore Medical Center
• Principal Investigator: Michael Argenziano, MD, FACS, Columbia University
• Principal Investigator: Mathew Williams, MD, Columbia University
• Principal Investigator: John G. Byrne, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01121263
• Other Study ID Numbers: GCO 09-0657; 1RC1HL100951
• First Posted: May 12, 2010
• Last Update Posted: Mar 14, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Icahn School of Medicine at Mount Sinai: coronary arteriosclerosis; coronary heart disease; coronary artery bypass; coronary artery bypass, off-pump; coronary angiography; drug-eluting stents
• Additional relevant MeSH terms: Coronary Artery Disease

Study Results

Participant Flow

Recruitment Details	Study Recruitment started in May 2010 and completed in November 2011 across 11 US medical centers that included adult patients with multivessel coronary artery disease and clinical indication for revascularization, who were candidates for both Hybrid Coronary Revascularization (HCR) and Percutaneous Coronary Intervention (PCI) with DES

Arm/Group Title	Cohort 2: Intervention Cohort - HCR Group (N=200)	Cohort 2: Intervention Cohort - PCI Group (N=98)
Arm/Group Description	Patients who underwent Hybrid Coronary Revascularization (HCR) with minimally invasive LIMA-LAD CABG	Patients who met proposed anatomic and clinical eligibility criteria and underwent multivessel Percutaneous Coronary Intervention (PCI) with drug eluting stents (DES)
Period Title: Overall Study
STARTED	200	98
COMPLETED	175	83
NOT COMPLETED	25	15

Baseline Characteristics

Arm/Group Title	Cohort 2: Intervention Cohort - HCR Group (N=200)	Cohort 2: Intervention Cohort - PCI Group (N=98)	Total
Arm/Group Description	Patients who underwent Hybrid Coronary Revascularization (HCR) with minimally invasive LIMA-LAD CABG	Patients who met proposed anatomic and clinical eligibility criteria and underwent multivessel Percutaneous Coronary Intervention (PCI) with drug eluting stents (DES)	Total of all reporting groups
Overall Participants	200	98	298
Age (years) [Mean (Standard Deviation) ]
Age	64.41 (11.78)	63.91 (10.82)	64.24 (11.46)
Sex: Female, Male (Count of Participants)
Female	48 24%	28 28.6%	76 25.5%
Male	152 76%	70 71.4%	222 74.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 5%	9 9.2%	19 6.4%
Not Hispanic or Latino	183 91.5%	83 84.7%	266 89.3%
Unknown or Not Reported	7 3.5%	6 6.1%	13 4.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 2%	3 3.1%	7 2.3%
Native Hawaiian or Other Pacific Islander	1 0.5%	0 0%	1 0.3%
Black or African American	28 14%	11 11.2%	39 13.1%
White	161 80.5%	83 84.7%	244 81.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 3%	1 1%	7 2.3%
Region of Enrollment (participants) [Number]
United States	200 100%	98 100%	298 100%

Outcome Measures

1. Primary Outcome

Title	Major Adverse Cardiac and Cerebrovascular Event (MACCE)
Description	For the purposes of this study MACCE is defined as a non-weighted composite score comprised of the following components: Death Stroke Myocardial Infarction Repeat Revascularization
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HCR Group (N=200)	PCI Group (N=98)
Arm/Group Description	Primary Outcome in Cohort 2: Intervention Cohort - HCR Group	Primary Outcome in Cohort 2: Intervention Cohort - PCI Group
Measure Participants	200	98
Any MACCE	23 11.5%	10 10.2%
Death	3 1.5%	1 1%
Myocardial Infarction	4 2%	3 3.1%
Stroke	5 2.5%	0 0%
Revascularization	14 7%	8 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HCR Group (N=200), PCI Group (N=98)
	Comments	This applies to any MACCE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Regression, Cox
	Comments	The Cox proportional hazards regression model was weighted by propensity score to adjust for differences in baseline risk between the two groups.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.063
	Confidence Interval	() 95%; 0.666 to 1.697
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Cox model was weighted by propensity score to adjust for differences in baseline risk between the two groups.

2. Secondary Outcome

Title	Major Adverse Cardiac and Cerebrovascular Event (MACCE)
Description	For the purposes of this study MACCE is defined as a non-weighted composite score comprised of the following components: Death Stroke Myocardial infarction Repeat revascularization
Time Frame	Occurence of MACCE through the end of study up to two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HCR Group (N=200)	PCI Group (N=98)
Arm/Group Description	Occurrence of MACCE through the end of study in Cohort 2: Intervention Cohort - HCR Group	Occurrence of MACCE through the end of study in Cohort 2: Intervention Cohort - PCI Group
Measure Participants	200	98
Any MACCE	23 11.5%	12 12.2%
Death	3 1.5%	2 2%
Myocardial Infarction	4 2%	3 3.1%
Stroke	5 2.5%	0 0%
Revascularization	14 7%	10 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HCR Group (N=200), PCI Group (N=98)
	Comments	This applies to any MACCE
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.868
	Confidence Interval	() 95%; 0.556 to 1.355
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Cox proportional hazards regression model was weighted by the propensity score to account for the difference in baseline risk between groups.

Adverse Events

Time Frame	Adverse events were reported throughout the period of trial participation for each study participant.
Adverse Event Reporting Description	Adverse events were documented and reported by staff at the study sites as they occurred per the protocol definitions.
Arm/Group Title	HCR Group (N=200)		PCI Group (N=98)
Arm/Group Description	Serious Adverse Events in Cohort 2: Intervention Cohort - HCR Group		Serious Adverse Events in Cohort 2: Intervention Cohort - PCI Group
All Cause Mortality
	HCR Group (N=200)		PCI Group (N=98)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	HCR Group (N=200)		PCI Group (N=98)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/200 (19.5%)		17/98 (17.3%)
Cardiac disorders
Cardiac Arrhythmias	6/200 (3%)	6	1/98 (1%)	1
Congestive Heart Failure	1/200 (0.5%)	2	1/98 (1%)	1
Cardiogenic Shock	0/200 (0%)	0	1/98 (1%)	1
Diastolic Heart Failure	0/200 (0%)	0	1/98 (1%)	1
Dresseler's Syndrome	1/200 (0.5%)	1	0/98 (0%)	0
Hypertension Resulting in Dizziness	1/200 (0.5%)	1	0/98 (0%)	0
IABP placed after becoming hypotensive	0/200 (0%)	0	1/98 (1%)	1
Myocardial Infarction	3/200 (1.5%)	4	3/98 (3.1%)	4
Revascularization	13/200 (6.5%)	14	10/98 (10.2%)	12
Gastrointestinal disorders
Acute viral gastroenteritis	1/200 (0.5%)	1	0/98 (0%)	0
GI Bleed	2/200 (1%)	2	0/98 (0%)	0
General disorders
Allergic reaction to antihypertensive drug	1/200 (0.5%)	1	0/98 (0%)	0
Atypical Chest Pain	1/200 (0.5%)	1	5/98 (5.1%)	5
Bleeding	1/200 (0.5%)	1	0/98 (0%)	0
Weakness and dizziness	0/200 (0%)	0	1/98 (1%)	1
Infections and infestations
Major Infection	6/200 (3%)	6	0/98 (0%)	0
Nervous system disorders
Stroke	4/200 (2%)	4	0/98 (0%)	0
Transient Ischemic Attack (TIA)	2/200 (1%)	2	0/98 (0%)	0
Psychiatric disorders
Post op deliriums/psychosis	1/200 (0.5%)	1	0/98 (0%)	0
Renal and urinary disorders
Benign prostatic hyperplasia with bladder obstruction	1/200 (0.5%)	1	0/98 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	3/200 (1.5%)	3	0/98 (0%)	0
Respiratory Failure	3/200 (1.5%)	3	1/98 (1%)	1
Vascular disorders
Percutaneous transluminal angioplasty of superficial femoral artery	1/200 (0.5%)	1	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	HCR Group (N=200)		PCI Group (N=98)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/200 (2.5%)		0/98 (0%)
Cardiac disorders
Cardiac Arrhythmias	1/200 (0.5%)	1	0/98 (0%)	0
Myocardial Infarction	1/200 (0.5%)	1	0/98 (0%)	0
Revascularization	1/200 (0.5%)	1	0/98 (0%)	0
Infections and infestations
Major Infection	1/200 (0.5%)	1	0/98 (0%)	0
Nervous system disorders
Stroke	1/200 (0.5%)	1	0/98 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

MSSM and sites shall cooperate in the submission of manuscript(s) for publication of the study results and sites shall not submit manuscripts for publication without express written permission of the Operations Committee. After dissolution of the Operations committee or one year after the completion of the agreement, whichever occurs first, no such permission shall be required.