TRANSCEND: Low-Dose DCB for PAD Still Looking Good at 2 Years

At 2 years, a next-generation, low-dose paclitaxel drug-coated balloon (DCB) continues to show good safety and efficacy compared with a standard high-dose paclitaxel DCB in the treatment of femoropopliteal artery disease, according to results from the TRANSCEND study.

In a presentation at VIVA 2022, Kenneth Rosenfield, MD (Massachusetts General Hospital, Boston), noted that there was sustained improvement in both treatment groups, with no deterioration from 12 months to 24 months, “which I think is important in all of these outcome measures demonstrating a durable result from both drug-coated balloons,” he added.

The multicenter TRANSCEND trial is comparing the investigational low-dose SurVeil DCB (Surmodics), which delivers a dose of 2.0 µg/mm² paclitaxel, and the IN.PACT Admiral DCB (Medtronic), which delivers 3.5 µg/mm² paclitaxel. Rosenfield said one unique feature of the low-dose DCB is that it was designed to have “substantially less particulate downstream than just about any other [DCB],” which may make a difference in terms of safety.

Safety concerns over the use of paclitaxel in the treatment of PAD first arose in 2018 with the publication of a meta-analysis of 28 RCTs, led by Konstantinos Katsanos, MD, PhD (Patras University Hospital, Rion, Greece), that showed excess late mortality starting at 2 years in patients treated with a paclitaxel-costed balloon or stent versus noncoated devices. Since then, study after study has refuted the mortality signal, including the large SAFE-PAD analysis with 5-year follow-up on more than 32,000 patients and the COMPARE trial of low- and high-dose paclitaxel-coated balloons.

Rosenfield said the 2-year TRANSCEND data demonstrate that the low-dose DCB, which is currently under review with the US Food and Drug Administration, “is noninferior to the market-leading IN.PACT Admiral DCB, and hopefully we will see approval of this device in the near future so we can get to the next-generation of DCB.” The trial has a planned follow-up of 60 months.

No Clinical or Functional Differences Seen

For TRANSCEND, Rosenfield and colleagues randomized 446 patients (mean age 67 years; 63% male) with femoropopliteal disease to the low-dose (n = 222) or high-dose DCB (n = 224). All were in Rutherford class 2-4, although those randomized to the low-dose DCB were statistically worse as a group than those randomized to the higher dose DCB (P = 0.013). Patients were treated at 52 clinical sites in the US and 13 international centers and were eligible if they had de novo or nonstented restenotic lesions ≤ 180 mm in length, between 4 and 7 mm in diameter, and were 70% stenosed or greater.

Follow-up to 24 months was completed in 94.2% of patients. Primary patency was 70.8% in the high-dose group and 70.4% in the low-dose group (log-rank P = 0.991), with the curves essentially superimposable on Kaplan-Meier analysis.

Similarly, there were no differences in the key secondary safety endpoint of freedom from device- and procedure-related death through 30 days post-index procedure and freedom from major target limb amputation and clinically driven TVR between the low- and high-dose DCBs (81.8% vs 83.2%; P = 0.0729). Clinically driven TLR also was similar at 14.7% in the low-dose group and 11.8% in the high-dose group (P = 0.453). There were no amputations in the low-dose group and one in the high-dose group.

Freedom from all-cause mortality was high in both groups: 91.6% with the low-dose DCB and 92.7% with the high-dose DCB (P = 0.661). In terms of functional outcomes, Rutherford classification change was similar between groups, with 88.5% of those in the low-dose group and 89.3% in the high-dose group improving by at least 1 grade at 24 months (P = 0.104).

Improvement in ankle brachial index was sustained and comparable between groups, with no differences between the 12-month and 24-month follow-up. Similarly, there was sustained improvement in both groups for the Walking Impairment Questionnaire and the Peripheral Artery Questionnaire.

Toxicity Concerns Persist for Some

Following the presentation, panelist Eric A. Secemsky, MD (Beth Israel Deaconess Medical Center, Boston, MA), asked if there really is a need to follow patients for 3 to 5 years to see if the low-dose DCB outperforms the higher-dose paclitaxel in terms of efficacy.

Rosenfield said he believes it is important for the purpose of understanding how the DCB performs in the therapeutic window over time, and in light of the potential for needing to use multiple devices in a single patient. Moreover, the long-term follow-up of DCBs used in the peripheral arteries is something the FDA has repeatedly said is needed for safety in the context of the signal from the Katsanos meta-analysis. Rosenfield noted that there's always a theoretical possibility of toxicity, adding “I think FDA remains somewhat concerned about it.”

Secemsky, who has led several studies trying to get to the bottom of the paclitaxel safety story, including multiple real-world Medicare analyses that found nothing to support the long-term mortality signal, told TCTMD that while he personally has no lingering concerns about paclitaxel use in peripheral interventions, some operators remain unconvinced and would likely find a low-dose version of a DCB appealing.

Still another issue is that “maybe the lowest dose needed is important, but I think we all are looking more at what gives us the best long-term improvement,” he added. “If the low-dose DCB truly works as well as the higher dose and there's any residual concern that paclitaxel dose is associated with adverse events—although to this point there is nothing to support that concern—then it might make sense. . . . But this device wasn't designed to be a low-dose option with the concern that there's adverse events at higher doses, because we’ve shown that there isn’t.”