Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease: 12-Month Results From the DANCE Clinical Trial
Does adventitial delivery of dexamethasone as an adjuvant to standard endovascular revascularization improve outcomes in femoropopliteal peripheral artery disease?
Adventitial delivery of dexamethasone may be an effective and safe therapy to prevent restenosis of femoropopliteal popliteal artery disease.
Razavi, M. K., Donohoe, D., D’Agostino, R. B., Jaff, M. R., & Adams, G. (2018). Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease. JACC: Cardiovascular Interventions, 11(10), 921-931. doi:10.1016/j.jcin.2017.12.015
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Study Design: Prospective, multicenter, single-arm, open-label study
Funding Source: Mercator MedSystems, Inc.
Setting: Multicenter, 27 US sites
The DANCE study enrolled 262 patients for a total of 283 limbs across 27 sites for the evaluation of adventitial delivery of dexamethasone as an adjunct to standard endovascular treatment of femoropopliteal PAD. The patient population consisted of more high-risk patients - increased calcification, popliteal artery involvement, complex TASCII B-D lesions and Rutherford category 4 disease – compared to those in the trials used to generate performance goals. Patients were categorized into two cohorts: atherectomy (ATX) and angioplasty (PTA). Adventitial access was achieved using the Bullfrog device in which a compliant balloon adapts to the vessel wall and a microneedle punctures into the perivascular tissue. An 80% dexamethasone to 20% contrast 3.2 mg/mL solution was used with an intended ratio of 1.6 mg drug per 1-cm of lesion length.
The overall 12-month primary patency in DANCE was 74.6% (95% CI 68.7-79.7%); 74.8% (66.6-81.5%) in the ATX cohort and 74.3% (65.6-81.5%) in the PTA cohort. This was noninferior to the 72.3% contemporary performance goal (met-analysis of pooled DCB studies) and superior to the 52.5% historical performance goal for both primary patency and intention to treat. ABI/TBI improved from baseline of 0.77 ± 0.24 to 12-month follow-up 0.94 ± 0.25 (p < 0.001). There were more stents placed in the DANCE trial than compared to pooled DCB studies however primary patency rates did not vary significantly in limbs with or without stents. There were no 30-day device or drug related severe adverse events. Of note, there was no concurrent control group that did not receive dexamethasone therapy.
Figure 5. The Kaplan-Meier estimates from (A) DANCE-ATX and (B) DANCE_PTA) are shown, with 12- and 130month data highlighted. ATX = atherectomy; CD-TLD = clinically driven targe lesion revascularization; DANCE = Dexamethasone to the Adventitia to Enhance Clinical Efficacy After Femoropopliteal Revascularization; PTA = percutaneous transluminal angioplasty.
Dexamethasone is known to down-regulate cells linked to inflammatory re-stenosis. The delivery of dexamethasone is not a new concept, previously studied with systemic dosing and coronary drug-eluting stents, however those studies showed mixed results. Moreover, the concentration delivered in this study is more than 30 times the dosage concentration delivered from prior coronary stents.
Nicole A. Keefe, MD
Department of Radiology and Medical Imaging
University of Virginia