Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial
Carotid revascularization for asymptomatic carotid stenosis by carotid endarterectomy (CEA) or carotid artery stenting (CAS) is common and costly. The rationale for incurring large national costs for revascularization of asymptomatic patients is based on the results of the previous studies all of which were done without comparison to modern intensive medical management.
CREST-2 is two parallel multi-center randomized, observer-blinded endpoint clinical trials. The study is assessing: 1) the treatment differences between MEDICAL management compared with CEA, and 2) the treatment differences between MEDICAL management compared to CAS. Each is a two-arm, randomized trial of approximately 1,240 asymptomatic patients with high-grade stenosis randomized to receive revascularization plus intensive medical management (CAS or CEA) versus intensive medical management alone (MEDICAL).
The study population is people aged >35 years old who have high-grade cervical carotid artery stenosis and who are confirmed to be asymptomatic. It is anticipated that approximately 2480 adult men and women will be enrolled.
The primary outcome is the composite of stroke plus death (S+D) within 44 days after randomization and ipsilateral ischemic stroke thereafter up to 4 years, and this composite endpoint will be estimated using Kaplan-Meier survival approaches. Statistical testing will employ superiority testing, with the null hypothesis that MEDICAL is equivalent to CAS or CEA versus the alternative that MEDICAL differs from CAS or CEA.
Secondary outcomes are: 1) the assessment if MEDICAL differs from CAS, and differs from CEA, to maintain the level of cognitive function at the 4-year assessment, 2) if there are treatment differences in the incidence of major stroke, minor stroke, disabling stroke, non-disabling stroke, and tissue-based stroke at 4-years, and 3) potential effect modification of the CAS or CEA versus MEDICAL differences, based on patient age, sex, severity of carotid stenosis, restenosis, risk factor level, and duration of asymptomatic period.
ROVERThe RObotic Vascular & Endovascular Registry
The objectives of the study are to allow the physician to use the commercially available
Magellan Robotic System and Magellan Robotic Catheters to navigate to the treatment targets
in the peripheral vasculature to:
- Determine the number of endovascular procedures consecutively performed with the
Magellan Robotic System to navigate to treatment targets in the peripheral vasculature
- Achieve stable and efficient system preparation and set-up times, navigation and
cannulation times of target vessels during endovascular procedures, and placement
of therapeutic equipment used to perform endovascular procedures.
- Achieve stable and reduced fluoroscopy time during the endovascular procedures.
- Determine the number of cases required to reach a "steady state," reduction or
predictable time in conducting peripheral interventional procedures using descriptive
(means, ranges) statistics to analyze the data.
This is a prospective and retrospective, multi-center, single arm, non-blinded, sequentially
enrolling data collection activity (for which Hansen Medical is providing funding). Only
patients scheduled to undergo endovascular procedures using the Magellan Robotic System will
be approached for enrollment.
Registry procedures will be conducted in accordance with the labeled indication for use of
the Magellan™ Robotic System.
Prior to the physician participating in the registry and prior to subject enrollment, all
participating physicians will be required to complete Hansen Medical's Magellan Robotic
Participating registry sites must have a commercially available Magellan Robotic System for
the treatment of patients.
Participating sites will be assigned a specific site numeric identification code by the
The information collected into the registry will be data related to the procedure in which
the Magellan System was used or planned to be used and may include patient follow-up data,
minimally 14 days(± 5 days)post procedure but also may include 30 day follow-up to assess
for the resolution of a procedural or post procedure adverse event.
The database will be a repository for the collected registry data and the data will be made
available (in extractable format) to the physician participants.
The data submitted will be reviewed on a regular basis for safety issues and complaints.
Adverse events and/or complaints deemed reportable will be submitted to the appropriate
regulatory agency/agencies by Hansen Medical, Inc.
Global Observational Study to Evaluate the Correlation Between Coronary and Carotid Atherosclerotic Disease (CAD) and Links with Clinical Outcomes
Observational study to collect F/U imaging & clinical endpoint data from pts. who successfully completed baseline coronary IVUS (intravascular ultrasound) imaging in the dal-PLAQUE 2 (DP2) study to determine the correlation & clinical relevance of such imaging as related to coronary artery disease (CAD). Pts. who have had baseline angiography/IVUS, with or w/o baseline carotid ultrasound but NOT undergone follow-up angiography/IVUS as part of DP2 will have F/U angiogram/IVUS within 18-27 mos. of baseline imaging. Pts. who have had baseline carotid ultrasound but NOT undergone a F/U carotid ultrasound as part of DP2 will have follow-up carotid ultrasound within 18-27 mos. of baseline imaging. Main objectives is to compare: extent of atherosclerosis in coronary arteries with the extent of atherosclerosis in carotid arteries at a single point in time. Pts. who have successfully undergone baseline IVUS imaging, with or w/o baseline carotid ultrasound, in DP2 will be included. Pts., who successfully completed baseline angiography/IVUS in DP2, with or w/o baseline carotid ultrasound, will be scheduled for final F/U angiography/IVUS any time between 18-27 mos. after DP2 baseline imaging. Pts. who successfully completed baseline carotid ultrasound in DP2 will be scheduled for F/U carotid ultrasound any time between 18 -27 mos. after DP2 baseline imaging. Endpoints: death, death from coronary heart disease, resuscitated cardiac arrest, non-fatal MI, stroke, hospitalization for documented acute coronary syndrome, coronary revascularization procedure & carotid artery surgery or angioplasty. Pts. will have annual phone contact for 3 yrs. to check for the occurrence of cardiovascular & cerebrovascular clinical endpoints. Imaging parameters from this study will be combined with the imaging data from DP2 to compare coronary & carotid atherosclerosis extent at baseline & rate of progression up to 2 yrs.
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
Evidence supporting a routine invasive practice paradigm for patients with stable ischemic
heart disease (SIHD) is outdated. In strategy trials conducted in the 1970s, coronary artery
bypass grafting (CABG) improved survival as compared with no CABG in SIHD patients with
high-risk anatomic features. The relevance of these studies today is speculative because
contemporary secondary prevention—aspirin, beta-blockers, statins, ACE inhibitors, and
lifestyle interventions—were used minimally if at all. Subsequent trials have compared
percutaneous coronary intervention (PCI) with medical therapy, as PCI has replaced CABG as
the dominant method of revascularization for SIHD. To date, PCI has not been shown to reduce
death or myocardial infarction (MI) compared with medical therapy in SIHD patients.
COURAGE and BARI 2D, the two largest trials comparing coronary revascularization vs. medical
therapy in SIHD patients, found that among patients selected on the basis of coronary
anatomy after cath, an initial management strategy of coronary revascularization (PCI, PCI
or CABG, respectively) did not reduce the primary endpoints of death or MI (COURAGE), or
death (BARI 2D) compared with OMT alone. These data suggest, but do not prove, that routine
cath--which often leads to ad hoc PCI through the diagnostic-therapeutic cascade--may not be
required in SIHD patients. However, most patients enrolled in COURAGE and BARI 2D who had
ischemia level documented at baseline had only mild or moderate ischemia, leaving open the
question of the appropriate role of cath and revascularization among higher risk patients
with more severe ischemia. Observational data suggest that revascularization of patients
with moderate-to-severe ischemia is associated with a lower mortality than medical therapy
alone, but such data cannot establish a cause and effect relationship. In clinical practice
only about half such patients are referred for cath, indicating equipoise. Furthermore,
analysis of outcomes for 468 COURAGE patients with moderate-to-severe ischemia at baseline
did not reveal a benefit from PCI. This issue cannot be resolved using available data
because all prior SIHD strategy trials enrolled patients after cath, introducing undefined
selection biases (e.g., highest risk patients not enrolled) and making translation of study
results problematic for clinicians managing patients who have not yet had cath.
A clinical trial in SIHD patients uniformly at higher risk (which could not have been
performed before COURAGE and BARI 2D results were available) is needed to inform optimal
management for such patients.
The study protocol is final, and was distributed to sites February 2012. Study protocol v2.0
was approved in January 2014.
- USA (~150 sites)
- Russian Federation
- New Zealand
- Saudi Arabia