NOVT, any comments on today's news?
Novoste Announces Results of BETA-CATH System Trial
Beta Radiation Shown to Reduce In-Lesion Restenosis in Balloon Angioplasty Patients in Largest Ever Trial of Vascular Brachytherapy
ORLANDO, Fla.--(BW HealthWire)--March 18, 2001--New research presented today at the 50th Annual Scientific Sessions of the American College of Cardiology shows that beta radiation significantly reduces the risk of in-lesion restenosis (recurrent blockage) for patients undergoing balloon angioplasty, when compared to patients treated with placebo. Results of the pivotal BETA-CATH(TM) System Trial, sponsored by Novoste Corporation (Nasdaq: NOVT - news), were presented today during the ACC's ``Late Breaking Clinical Trials'' session by Richard E. Kuntz, M.D., Chief of the Division of Clinical Biometrics, Brigham and Women's Hospital in Boston, Massachusetts.
While the primary clinical endpoint of the overall trial did not demonstrate a significant benefit of beta radiation when the two branches of the trial (balloon and stent) were combined, beta radiation was shown to significantly reduce the risk of angiographic restenosis in the lesion for patients undergoing either balloon angioplasty or stent implantation, when compared to the placebo group.
As Principal Investigator of the study, Dr. Kuntz observed, ``This is statistically the most powerful trial of coronary radiation performed to date. While the clinical results did not reach statistical significance in the total cohort combining the PTCA and stent patients, the results of the stand-alone PTCA branch were very encouraging. Here, in-lesion restenosis was significantly reduced with beta radiation, and the clinical outcomes demonstrated a very positive trend. This is particularly impressive since the PTCA branch was not originally statistically powered to prove a significant improvement in clinical endpoints by itself. In the stented patients, radiation had a positive effect on preventing restenosis at the initial lesion site, but had a negative effect on the adjacent edges, leading to higher clinical restenosis compared with placebo.''
Commenting further, Dr. Kuntz said, ``Radiation has become established as the treatment of choice for patients with in-stent restenosis. I believe that many facets of this trial suggest that beta radiation may be promising as an extension for de novo lesions in patients at a higher risk of restenosis undergoing balloon angioplasty and stenting, once the issue of edge restenosis is resolved.''
Background
Of the 800,000 people who undergo coronary angioplasty each year in the United States, about 75 percent of patients will receive coronary stents. Many of these patients, approximately 150,000 per year, will later suffer from recurrent blockage inside their stents, a condition known as ``in-stent restenosis.'' Multiple randomized clinical trials, sponsored by Novoste and others, have previously demonstrated the effectiveness of intracoronary radiation in the ``secondary prevention'' of restenosis, i.e. reducing the incidence of a second restenosis in patients who have already restenosed the first time after stent placement.
Until now, intracoronary radiation has not been evaluated for the ``primary prevention'' of restenosis in a randomized, placebo-controlled clinical trial.
Trial Design
Designed in 1996 and begun in July 1997, the BETA-CATH System Trial was the first randomized, multicenter, placebo-controlled study of vascular brachytherapy. Vascular brachytherapy is radiation therapy delivered inside an artery with the objective of reducing the incidence of restenosis. The Trial is also the first pivotal study to evaluate intracoronary radiation in the primary prevention of coronary restenosis subsequent to either PTCA (``percutaneous transluminal coronary angioplasty'' or ``balloon angioplasty'') or first time stent placement.
The BETA-CATH System Trial was originally designed to enroll 1,100 patients into one of two branches, either the PTCA branch or the Provisional Stent branch. According to the clinical trial protocol, patients enrolled in the trial were initially treated with balloon angioplasty. If the cardiologist achieved a satisfactory result, the patient would remain in the PTCA branch and then be treated with the BETA-CATH System. If balloon angioplasty was sub-optimal, the patient would be entered into the Provisional Stent branch. Prior to stent placement, the patient would be treated with the BETA-CATH System, after which a stent would be implanted. All patients were randomized to either an inactive (placebo) or active 30-mm Strontium-90 (beta radiation) source train, and treatment times ranged from two to four minutes.
In March 1999, the trial's Data Safety and Monitoring Board proposed creating a new stent branch comprised of only those patients receiving a longer duration of anti-platelet therapy (APT), a change first implemented by Novoste in November 1998 to address late stent thrombosis concerns. Patient recruitment continued until September 1999, at which time 1,455 patients had been enrolled into the trial at 59 investigational sites in North America and Europe.
On average, patients enrolled in the study had 12.5-mm long lesions in arteries 3.0-mm in diameter. Depending on the artery diameter, a dose of either 16 or 21 gray was administered. Patients returned for follow-up examinations eight months after the vascular brachytherapy procedure.
Data Presentation
The trial was first analyzed by comparing the clinical outcomes of the total radiation cohort (those receiving either PTCA or a stent with extended APT) to the overall placebo group. Then the data was analyzed by reviewing the PTCA and the stent branches individually. The clinical data from the total combination of PTCA and stent patients is as follows.
BETA-CATH(TM) System Trial Clinical Data
Combined Group: PTCA + Stent (Extended APT) Branches
Beta Radiation Placebo
(N = 492) Control Percent
Clinical Outcomes (N = 464) Difference
Target Lesion
Revascularization (TLR) 13.7% 15.4% (12%)
Target Vessel
Revascularization (TVR) 15.6% 17.4% (10%)
Major Adverse Cardiac
Events (MACE) 18.7% 20.6% (9%)
In this combined group of PTCA and stent patients, those who
received beta radiation exhibited modest improvements in their
clinical endpoints, although not statistically significant. Upon
analysis of the two trial branches as discussed below, it was clear
that patients in the PTCA branch clinically benefited more from
radiation than did those in the Stent branch, thereby leading to a
less pronounced effect when the two branches were combined.
BETA-CATH(TM) System Trial Data: PTCA Branch
Beta Radiation Placebo
(N = 264) Control Percent
Angiographic Results (N = 240) Difference
Restenosis Rate:
Lesion Segment 21.4% 34.3% (38%)
Analysis Segment 31.0% 36.0% (14%)
Clinical Outcomes
Target Lesion
Revascularization (TLR) 10.0% 15.3% (35%)
Target Vessel
Revascularization (TVR) 12.3% 17.0% (28%)
Major Adverse Cardiac
Events (MACE) 14.2% 20.4% (30%)
In the PTCA branch, restenosis in the legion segment was
significantly reduced by 38% in the group receiving radiation versus
placebo. In addition, the effect of beta radiation on all clinical
outcomes in the PTCA branch demonstrated a strong positive trend.
BETA-CATH(TM) System Trial Data: Stent w/extended APT Branch
Beta Radiation Placebo
(N = 228) Control Percent
Angiographic Results (N = 224) Difference
Restenosis Rate:
Lesion Segment 21.1% 33.0% (36%)
Analysis Segment 44.9% 35.3% 21%
Clinical Outcomes
Late Stent Thrombosis 1.3% 1.3% 0%
Target Lesion
Revascularization (TLR) 18.0% 15.5% 14%
Target Vessel
Revascularization (TVR) 19.4% 17.7% 9%
Major Adverse Cardiac
Events (MACE) 23.9% 20.8% 13%
In the Stent branch, angiographic restenosis in the lesion was also reduced significantly (by 36%) as in the PTCA branch; however, radiation did not improve restenosis in the much longer analysis segment. This was likely due to `geographic miss', the mismatch of the radiation source train relative to the placement of the stent, which was implanted after the radiation catheter was removed. In reviewing the clinical endpoints of the Stent branch, the data did not show a beneficial effect of radiation on improving outcomes. The incidence of late thrombosis, however, was the same (1.3%) in both the radiation and the placebo groups, indicating that the extended antiplatelet therapy resolved the problems of thrombosis observed in the original stent branch.
William A. Hawkins, President & CEO of Novoste, remarked, ``As a pioneer in the field, Novoste has led the way in discovering the opportunities and challenges of vascular brachytherapy. We were the first to demonstrate the opportunity for beta radiation to treat patients with in-stent restenosis, and our BETA-CATH System is being used worldwide to treat more and more of these patients everyday.''
Hawkins continued, ``As a part of Novoste's commitment to rigorous clinical evaluation of vascular brachytherapy, we were the first to discover the initial challenge of late stent thrombosis in late 1998. We responded to the issue by expanding the study to include a third branch to determine whether longer duration antiplatelet therapy would address the late stent thrombosis problem, and the results of this trial clearly demonstrate that it does.''
``Additionally, Novoste has previously identified the importance and methods of avoiding geographic miss, which may result in a sub-optimal dose of radiation outside the lesion. At the time this trial was designed, over four years ago, we did not understand this issue and as a consequence there was a high incidence of geographic miss in this trial. This probably led to a less pronounced treatment effect over the full analysis segment (which extended beyond the radiation zone) because there were areas of the vessel that were revascularized but not irradiated. We remain committed to further advancing the science and applications of this important therapy for patients with coronary disease.''
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