Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization

Abstract

Objective: Restenosis following endovascular treatment of the femoropopliteal segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. Although local drug delivery to the superficial femoral and popliteal arteries promises improved patency, data are currently limited. We hypothesized that improved percutaneous delivery of an anti-inflammatory compound into the adventitia of the femoropopliteal at the time of endovascular treatment would be safe, feasible, and decrease the inflammatory response.

Methods: This was a prospective, investigator-initiated, phase I, first-in-man study testing the safety and feasibility of percutaneous adventitial delivery of dexamethasone. Following successful intervention, an adventitial microinfusion catheter was advanced over a 0.014-inch wire to the treated segment. Its microneedle (0.9 mm long × 140-μm diameter) was deployed into the adventitia to deliver dexamethasone (4 mg/mL) mixed with contrast agent (80:20 ratio), providing fluoroscopic visualization. The primary safety outcome measure was freedom from vessel dissection, thrombosis, or extravasation while the primary efficacy outcome was duplex-determined binary restenosis defined as a peak systolic velocity ratio >2.5.

Results: Twenty patients with Rutherford clinical category 2-5 enrolled in this study. The mean age was 66, and 55% had diabetes mellitus. Treated lesion length was 8.9 ± 5.3 cm, and 50% were chronic total occlusions. Eighty percent of treated lesions were in the distal superficial femoral or popliteal arteries. All lesions were treated by balloon angioplasty with provisional stenting (n = 6) for suboptimal result. Three patients were treated with atherectomy as well. A mean of 1.6 ± 1.1 mg (0.5 ± 0.3 mL) of dexamethasone sodium phosphate was injected per centimeter of lesion length. In total, a mean of 12.1 ± 6.1 mg of dexamethasone was injected per patient. The mean number of injections required per lesion was 3.0 ± 1.3 cm, minimum one and maximum six injections. There was 100% technical success of drug delivery and no procedural or drug-related adverse events. The mean Rutherford score decreased from 3.1 ± .7 (median, 3.0) preoperatively to .5 ± .7 at 6 months (median, 0.0; P < .00001). Over this same time interval, the index leg ankle-brachial index increased from .68 ± .15 to .89 ± .19 (P = .0003). The preoperative C-reactive protein in this study was 6.9 ± 8.5 indicating severe baseline inflammation, which increased to 14.0 ± 23.1 mg/L (103% increase) at 24 hours following the procedure. However, this increase did not reach statistical significance of P = .14. Two patients met the primary efficacy end point of loss of primary patency by reoccluding their treated segment of the index lesion during the follow-up period.

Conclusions: Adventitial drug delivery via a microinfusion catheter is a safe and feasible alternative to intimal-based methods for adjunctive treatment in the femoropopliteal segment. The 6-month preliminary results suggest perivascular dexamethasone treatment may improve outcomes following angioplasty to the femoral and popliteal arteries, and support further clinical investigation of this approach.

Trial registration: ClinicalTrials.gov NCT01507558.

Conflict of interest statement

Author conflict of interest: none

Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1

The Bullfrog micro-infusion catheter, A. Diffusion grading scale, B. Figure 1A supplied courtesy of Mercator Medsystems, San Leandro, Cal.

Figure 2

Endovascular treatment with adjunctive dexamethasone. This is a 49 year old man with severe disabling claudication and a 16 cm superficial femoral artery occlusion. Following securing access across the lesion with a glide wire, the lesion was treated with balloon angioplasty. Following successful angioplasty, four 1.0 ml injections were performed along the length of the lesion (only 3 shown). In the left panel there is a discreet contrast blush seen at each injection site. Note that the contrast appears circumferentially at each injection site. Three minutes later, the drug-contrast admixture can be seen to have diffused longitudinally to fully cover the treated segment. The patient is now 2 years from his index procedure and remains and complains of only mild claudication with heavy exertion. He has an ankle-brachial index of 1.09 and a peak systolic velocity ratio of less than 2.5.

Figure 3

Examples of typical dexamethasone-contrast diffusion patterns in patients treated in this study.

Figure 4

The mean ankle-brachial index (ABI) is significantly improved from baseline across all time points post procedure.