CREST trial: Hurdles overcome
CREST trial: Hurdles overcome
Thu, 13 Feb 2003 23:45:00
Phoenix, AZ - After some near-crippling early hurdles, the Carotid Revascularization vs Stenting Trial (CREST) is now under way, and investigators are reporting good initial results from lead-in cases. An interim report on this pivotal trial was presented here at the American Stroke Association's 28th International Stroke Conference.
The main problem with enrollment to date has been that CRESTdespite its being an NIH-funded trialwas launched before the Health Care Financing Administration (HCFA) had assessed carotid stenting as an investigational procedure and had agreed to fund it, said Dr L Nelson Hopkins (State University of New York at Buffalo).
"HCFA just took a hard line and said 'We're not funding this,'" Hopkins told heartwire. "If you do a carotid stent, not only are you not going to get paid, but the hospital's not going to get paid. So talk about putting the brakes on something, that really did."
It has taken a year and a half, he says, to get the Centers for Medicare and Medicaid Services (CMS) to address the problem and resolve it. Traditionally, these agencies don't work together, he said, but "they've recognized the issue and begun to address it."
Most of the hurdles, which he described as "extraordinary," have now been overcome, and "it's finally getting to the point where it's ready to take off." Only 8 or 10 sites are currently randomizing patients, Hopkins said, but "when we get 25 sites randomizing patients, we ought to be cookin'."
Standard of care
During the 1990s, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) established carotid endarterectomy as the standard of care to relieve carotid obstruction and prevent stroke in patients with both symptomatic and asymptomatic high-grade carotid stenoses. More and more, carotid stenting using distal embolic protection has been used in high-risk patients who are not candidates for surgery with good results.
Recently, results of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, presented at the American Heart Association Scientific Sessions 2002, showed superior results with stenting in patients with significant comorbidities. However, what is not known is how stenting with distal protection compares with surgery in stroke prevention among the relatively young and healthy patients who were enrolled in NASCET and ACAS. CREST is meant to be the trial that provides that important information.
The trial is designed as a head-to-head comparison of the efficacy of endarterectomy vs stenting in the prevention of stroke over a follow-up period of up to 4 years, with attention to any differential efficacy of the procedures in male and female patients.
The lead-in phase has involved credentialing of interventionalists, requiring them to have done up to 20 cases with a low rate of adverse events before they participate in the trial. "It's a very significant technical hurdle to overcome and a learning curve that is very steep for people," Hopkins said. This laborious credentialing process has been the source of further delays, he added, as has the development of the technologies involved.
Investigators will use the Guidant ACCULINK® carotid stent with the ACCUNET® embolic filtration system.
In the study, 2500 patients will be randomized, giving researchers power to detect a greater than 1.2% per year absolute difference in primary end points. Eligible patients have had a transient ischemic attack (TIA) or nondisabling stroke in the past 180 days and have an ipsilateral carotid stenosis of 50% or greaterthat is, 50% or greater by angiography or 70% or greater by ultrasound.
"The reason for that is more and more patients today are undergoing endarterectomy by vascular surgeons without any other studies other than ultrasound, so it would be unfair to demand angiography given the fact that the ACAS study did show a significant risk of angiography," Hopkins said. However, because ultrasound often overestimates the degree of stenosis, they are using 70% for stenoses measured this way.
Finally, there must be an expectation to deliver the stent to the lesion, which is not always possible. Primary end points include periprocedural end points of 30-day stroke in either hemisphere, death, MI, and postprocedural ipsilateral stroke.
Comparable results
Current enrollment statistics show 331 patients in the lead-in phase, with 29 patients randomized. Despite the early delays, Hopkins said, CREST is now "doing okay," enrolling over 1 patient per month, which compares favorably with other trials in this area, including NASCET and SAPPHIRE.
To date, 28 centers have been approved for the lead-in phase and 23 centers have been approved as CREST sites. As of December 2002, 272 lead-in cases had been performed by 47 interventionalists, Hopkins said. The 30-day rates of stroke and death in this group are 1.8% in the asymptomatic patients and 6.6% in the symptomatic patients, for an overall rate of 3.6%, which he said, "compares favorably with known trials."
"In this lead-in phase, there is no clustering of serious adverse events at any individual center," he concluded. "The credentialing process appears appropriate and vigorous, with even distribution of serious adverse events among interventionalists, independent of their specialty, which is another interesting phenomenon."
Phoenix, AZ - After some near-crippling early hurdles, the Carotid Revascularization vs Stenting Trial (CREST) is now under way, and investigators are reporting good initial results from lead-in cases. An interim report on this pivotal trial was presented here at the American Stroke Association's 28th International Stroke Conference.
The main problem with enrollment to date has been that CRESTdespite its being an NIH-funded trialwas launched before the Health Care Financing Administration (HCFA) had assessed carotid stenting as an investigational procedure and had agreed to fund it, said Dr L Nelson Hopkins (State University of New York at Buffalo).
"HCFA just took a hard line and said 'We're not funding this,'" Hopkins told heartwire. "If you do a carotid stent, not only are you not going to get paid, but the hospital's not going to get paid. So talk about putting the brakes on something, that really did."
It has taken a year and a half, he says, to get the Centers for Medicare and Medicaid Services (CMS) to address the problem and resolve it. Traditionally, these agencies don't work together, he said, but "they've recognized the issue and begun to address it."
Most of the hurdles, which he described as "extraordinary," have now been overcome, and "it's finally getting to the point where it's ready to take off." Only 8 or 10 sites are currently randomizing patients, Hopkins said, but "when we get 25 sites randomizing patients, we ought to be cookin'."
Standard of care
During the 1990s, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) established carotid endarterectomy as the standard of care to relieve carotid obstruction and prevent stroke in patients with both symptomatic and asymptomatic high-grade carotid stenoses. More and more, carotid stenting using distal embolic protection has been used in high-risk patients who are not candidates for surgery with good results.
Recently, results of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, presented at the American Heart Association Scientific Sessions 2002, showed superior results with stenting in patients with significant comorbidities. However, what is not known is how stenting with distal protection compares with surgery in stroke prevention among the relatively young and healthy patients who were enrolled in NASCET and ACAS. CREST is meant to be the trial that provides that important information.
The trial is designed as a head-to-head comparison of the efficacy of endarterectomy vs stenting in the prevention of stroke over a follow-up period of up to 4 years, with attention to any differential efficacy of the procedures in male and female patients.
The lead-in phase has involved credentialing of interventionalists, requiring them to have done up to 20 cases with a low rate of adverse events before they participate in the trial. "It's a very significant technical hurdle to overcome and a learning curve that is very steep for people," Hopkins said. This laborious credentialing process has been the source of further delays, he added, as has the development of the technologies involved.
Investigators will use the Guidant ACCULINK® carotid stent with the ACCUNET® embolic filtration system.
In the study, 2500 patients will be randomized, giving researchers power to detect a greater than 1.2% per year absolute difference in primary end points. Eligible patients have had a transient ischemic attack (TIA) or nondisabling stroke in the past 180 days and have an ipsilateral carotid stenosis of 50% or greaterthat is, 50% or greater by angiography or 70% or greater by ultrasound.
"The reason for that is more and more patients today are undergoing endarterectomy by vascular surgeons without any other studies other than ultrasound, so it would be unfair to demand angiography given the fact that the ACAS study did show a significant risk of angiography," Hopkins said. However, because ultrasound often overestimates the degree of stenosis, they are using 70% for stenoses measured this way.
Finally, there must be an expectation to deliver the stent to the lesion, which is not always possible. Primary end points include periprocedural end points of 30-day stroke in either hemisphere, death, MI, and postprocedural ipsilateral stroke.
Comparable results
Current enrollment statistics show 331 patients in the lead-in phase, with 29 patients randomized. Despite the early delays, Hopkins said, CREST is now "doing okay," enrolling over 1 patient per month, which compares favorably with other trials in this area, including NASCET and SAPPHIRE.
To date, 28 centers have been approved for the lead-in phase and 23 centers have been approved as CREST sites. As of December 2002, 272 lead-in cases had been performed by 47 interventionalists, Hopkins said. The 30-day rates of stroke and death in this group are 1.8% in the asymptomatic patients and 6.6% in the symptomatic patients, for an overall rate of 3.6%, which he said, "compares favorably with known trials."
"In this lead-in phase, there is no clustering of serious adverse events at any individual center," he concluded. "The credentialing process appears appropriate and vigorous, with even distribution of serious adverse events among interventionalists, independent of their specialty, which is another interesting phenomenon."
|