CLINICAL: Clinical Studies & Trials

VERDICT (Vascular Evaluation for Revascularization: Defining the Indications for Coronary Therapy: A Pilot Study) was a prospective, global, multicenter study sponsored by Volcano to determine the correlation between fractional flow reserve (FFR) and Intravascular Ultrasound with VH^®IVUS in patients with intermediate coronary lesions. Up to 292 patients (for 302 lesions) at approximately 15 sites in Europe, South Africa and U.S. were enrolled in this study. The primary study objective was to establish the correlation between FFR and VH IVUS-derived parameters in patients with intermediate coronary lesions (≥40% to <80% diameter stenosis, as visually assessed by angiography). Specifically, to determine the extent to which pull back, lesion length, and VH TCFA plaque type improve the correlation between FFR and MLA. Patients will be followed for 3 years. Enrollment completed in April 2012. The merged data set from VERDICT and FIRST were presented at TCT 2012. The study was sponsored by Volcano and Volcano IVUS and Functional Management products were used.

ADAPT-DES (Assessment of Dual Anti-Platelet Therapy with Drug-Eluting Stents). Volcano participated in the ADAPT-DES trial being conducted in 11 sites in both the U.S. and Europe. ADAPT-DES is a prospective registry of 8,583 patients with coronary artery disease undergoing stent assisted intervention using DES. The objective of the study was to determine the frequency, timing and correlates (clinical and angiographic) of drug eluting stent thrombosis in the study population and the relationship of aspirin and/or clopidogrel response in this population. There was an IVUS sub-study that included 3,349 patients to determine whether one or more IVUS parameters are independent predictors of stent thrombosis. Enrollment goal was met and index results were discussed at TCT 2011 with final results presented most recently at the 2012 TCT meeting in Miami. The clinical results of this milestone study may be found on the last page of this report.

FIRST (Fractional Flow Reserve and Intravascular Ultrasound RelationShip Study) This was a multi-center, prospective registry of patients with intermediate coronary lesions defined as a stenosis of 40-80% by angiography. Approximately 350 patients were enrolled into the study at sites in the United States and Europe. There was no follow up beyond hospital discharge in this study. The objective was to evaluate the relationship between VH IVUS anatomical parameters and FFR value in patients with intermediate coronary stenoses, and to determine the VH IVUS anatomical criteria and cutoff value associated with significantly functional criteria of FFR<0.8. Enrollment was completed with results presented at TCT 2011. The data was then merged with the VERDICT study and was presented at TCT 2012. Volcano was the sponsor of this study and Volcano IVUS and Functional Management products were used.

ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) is a randomized controlled trial that will study 8,000 patients with stable ischemic heart disease (SIHD) and moderate to severe ischemia. Patients will be randomized to invasive strategy with catheterization/revascularization plus optimal medical therapy (OMT) vs conservative strategy with OMT and catheterization reserved for refractory symptoms or ACS. The study, funded by one of the largest grants ever awarded by the NIH/NHLBI for a comparative effectiveness trial, will enlist the collaboration of more than 150 medical centers around the U.S. and hundreds of sites in 33 countries worldwide. The ISCHEMIA trial enriches the population of patients enrolled by requiring documented proof of ischemia using non-invasive methods prior to enrollment and FFR during the procedure. Enrollment started in Q3 of 2012 and is expected to continue for several years.

EXCEL Evaluation of XIENCE PRIME™ or XIENCE V^® versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization Understanding the Disease Process . The EXCEL study, sponsored by Abbott Vascular is a Prospective, un-blinded, randomized multicenter trial of approximately 2600 subjects with unprotected left main coronary artery disease and treatment groups of stenting with XIENCE PRIME or XIENCE V Everolimus Eluting Coronary Stent System versus coronary artery bypass grafting. It is being conducted in approximately 165 sites globally and started enrollment in Q3 2011. Enrollment is expected to continue through Q1 2014. Following diagnostic angiography demonstrating significant left main disease and consensus of the Heart Team that the subject meets the study entry criteria, subjects will be consented and randomized 1:1 to:

a) PCI using the XIENCE PRIME or XIENCE V EECSS (n=1250), or
b) CABG (n=1250).

Follow-up for all randomized subjects will continue for five years with an option for additional follow-up to 10 years.

An additional group of approximately 1000 consecutive subjects with angiographically significant left main disease treated by participating qualified investigators during the course of this study who are either not eligible for randomization or for other reasons are not randomized will be consented for the Universal Registry, and followed until the time of initial treatment per standard of care with either PCI, CABG or medical therapy (or hospital discharge, whichever occurs earlier).

CAIN (Canadian Atherosclerosis Imaging Network) Correlation between coronary and carotid atherosclerotic disease and links with clinical outcomes is a prospective, multi-center imaging study expecting to enroll approximately 2000 patients scheduled for clinically-indicated coronary angiography. The objectives are to compare the atherosclerosis present in the coronary vasculature with the extent of atherosclerosis present in the carotid vasculature, compare the rate of disease progression in the coronary and carotid vasculature, and to characterize the association between changes in the coronary and carotid vasculature measurements from baseline to 24 months. Patients will undergo a coronary intravascular ultrasound (IVUS) examination and a carotid ultrasound examination (the latter allowing measurements of the intimal-medial thickness and 3-D ultrasound assessment of carotid plaque burden). Following a 24-month follow-up period, patients will then undergo repeat coronary intravascular ultrasonography and standard invasive coronary angiography as well as carotid ultrasound examination Patients will also be contacted by phone on an annual basis for 5 years to collect cardiovascular and cerebrovascular events.

AQUARIUS (Aliskiren QUantitative Atherosclerosis Regression Intravascular Ultrasound Study), is a randomized, double blind study to evaluate the efficacy and safety of aliskiren on the progression of atherosclerosis in patients with coronary artery disease in addition to optimal background therapy. The study is sponsored by Novartis. It will be conducted in approximately 10 countries and will enroll approximately 600 patients. The primary objective is to measure the change in the progression of coronary atherosclerosis (defined as change from baseline in percent atheroma volume) as assessed by IVUS. Approximately 50 of the sites will be using Volcano s5™ IVUS systems to obtain the images. Enrollment has started and will include two year follow up.

ASSURE (ApoA1 Synthesis Stimulation in AcUte CoRonary SyndromE Patients) is a Phase IIb multi-center, double-blind, randomized, parallel group, placebo-controlled clinical trial for the assessment of coronary plaque changes with RVX000222 as determined by intravascular ultrasound. It will be conducted in up to 60 sites worldwide and enroll patients that require a clinically indicated coronary angiography who are currently, or will be started on statin therapy and have a low level of HDL-C. Enrollment started this year, and is expected to be completed with follow up mid 2013.

VERDICT & FIRST Data Merge
VERDICT - Vascular Evaluation for Revascularization: Defining the Indications for Coronary Therapy: A Pilot Study FIRST-Fractional Flow Reserve and Intravascular Ultrasound RelationShip Study

Clinical Results
These two studies were combined to make a stronger data set of 516 patients, 544 intermediate lesions, a manuscript is under preparation.

ADAPT
Assessment of Dual Anti-Platelet Therapy with Drug-Eluting Stents. This study represents the current practice patterns based on the type of stents implanted and the type of medication regime the patient are to follow. This large data set concluded that using IVUS guided PCI (primary coronary intervention) is safe and generated better clinical outcomes even in high risks groups. Volcano IVUS influenced the change of therapy 75% of the time mostly in deciding to place larger or longer stents and using IVUS to determine stent apposition resulting in stent dilatation.

Clinical Outcome Results
Multi-center global registry with >8,500 consecutive patients

3,349 patient’s PCI with IVUS Guided PCI vs. Angio-alone in this study resulted in;

Both Acute (<30 days) and One-Year Follow-up IVUS-Guided PCI vs Angio-alone Resulted in:

33% Reduction in MI
50% Reduction in ST
38% Reduction in Ischemic TVR

Additional Clinical findings

No additional stents
Longer, appropriately sized stents without
increasing Peri-procedural-MI