The RANGER II SFA trial focused on treating disease in the superficial femoral and proximal popliteal arteries. Can you describe the disease typically seen in these vessels and the challenges of treatment?
The focus of the RANGER II SFA study was primarily on patients with intermittent claudication (Rutherford 2 and 3) and a minority of patients with rest pain (Rutherford 4). Most patients with claudication have obstructive disease in the femoropopliteal segment, although some patients have multi-level disease, especially those with critical limb ischemia. Disease in the femoropopliteal segment is heterogeneous, ranging from short segment stenoses to long chronic total occlusions. The plaque can be soft or heavily calcified. The clinical goal of endovascular therapy is to provide symptom relief. The angiographic goal is to not only provide a good result acutely, but also to maximize long-term patency. Patients with claudication and disease in the femoropopliteal segments will often survive for several years, perhaps decades, beyond the index intervention. Thus, it is important to ensure that the treatment offered is sustainable and minimizes the number of repeat procedures that patients will need to undergo. This is where drug-coated balloons (DCBs) come in – to improve the long term patency and clinical outcomes after endovascular therapy.
What is unique about the Ranger DCB?
The Ranger is a paclitaxel-coated balloon on a Sterling Balloon platform. It features the Transpax coating with a paclitaxel dose of 2 micrograms/mm2. A unique feature is that the balloon comes on an 0.018-inch platform rather than a 0.035-inch platform. The Ranger will be the first balloon available in the U.S. on a smaller platform. We look forward to FDA approval, hopefully in the near future.
Can you describe the RANGER II SFA trial?
The trial included 376 patients and was randomized 3:1, which means that for every 3 patients who were treated with a DCB,
1 patient was treated with standard balloon angioplasty. All patients were followed out to 12 months, which was the primary endpoint. Of the 376 patients in the study, 278 received a Ranger DCB and 98 received the standard angioplasty balloon. Twelve-month follow-up has been completed for 226 patients who received the DCB and 80 patients who received the standard angioplasty balloon. These 306 patients who have completed one-year follow-up constitute a cohort undergoing a pre-specified interim analysis, which was pre-determined in conjunction with the FDA, and which is sufficiently powered for the effectiveness and safety endpoints. An additional 12 patients were included in a pharmacokinetic substudy.
Why is it important that the interim analysis point was pre-specified?
If an interim analysis is contemplated, the point at which this is going to be performed must be decided upfront, otherwise the results are not statistically valid. If an interim analysis is not pre-specified, it loses statistical validity. The RANGER II SFA trial pre-specified an interim analysis once 75% of patients had completed one-year follow-up, and this was approved by the FDA.
What were highlights from the trial results?
RANGER II SFA had two endpoints — one was effectiveness, referring to patency, and the other endpoint was safety. Effectiveness in terms of patency at 12 months was 82% for the Ranger DCB and 68.8% for the standard angioplasty. In a Kaplan-Meier format, the patency at 12 months was 89.2% for the DCB arm and 72.9% for the angioplasty arm, which was statistically significant. The 12-month clinically driven target lesion revascularization rate (cd-TLR), was 6% for the DCB arm and 17.9% for the angioplasty arm. The other endpoint of the RANGER II SFA trial was safety. There has been a focus on potential signals of higher mortality with paclitaxel as compared to non-paclitaxel coated devices at three and five years. Right now, we have only one-year data from the RANGER II SFA trial, but we saw no difference in mortality between the drug-coated arm and the angioplasty arm at one year (Figure 1).
Can you talk about the pharmacokinetics substudy included in the trial?
Twelve patients were included in the pharmacokinetic substudy. One hour after the index procedure, the plasma paclitaxel level was undetectable in 11 out of 12 patients. At 3 hours post procedure, the plasma paclitaxel level was undetectable in all 12 patients. These findings suggest that the delivery of the drug was efficient.
Any final thoughts?
The Ranger is currently available in Europe and in Australia. In the United States, there are three DCBs available, and the Ranger, once FDA approved, will be the fourth. The benefit of paclitaxel coating does not appear to be a class effect, as the three available DCBs have different patency rates at one year. However, it is important to emphasize that these are not head-to-head comparisons, and the baseline demographic and angiographic features for patients enrolled in these trials were different.
Disclosure: Dr Sachar reports receiving honoraria from Boston Scientific for consulting, research, and educational activities
Address for correspondence: Ravish Sachar, MD, can be contacted at email@example.com