Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization.
Safety and feasibility of adjunctive dexamethasone infusion into the adventitia of the femoropopliteal artery following endovascular revascularization.
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DOI：
10.1016/j.jvs.2013.10.051
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发表时间：
2014-04
影响因子：
4.3
通讯作者：
Grenon, S. Marlene
中科院分区：
文献类型：
--
作者：
Owens, Christopher D.;Gasper, Warren J.;Walker, Joy P.;Alley, Hugh F.;Conte, Michael S.;Grenon, S. Marlene
股腘动脉（fem-pop）段血管内治疗后的再狭窄与手术时动脉壁产生的炎症反应相关。虽然局部药物输送到股浅动脉和腘动脉有望改善通畅性，但目前数据有限。我们假设，在血管内治疗时，改善经皮将抗炎化合物输送到股动脉外膜是安全、可行的，并可减少炎症反应。这是一项前瞻性、促凝剂启动、I期、首次人体研究，旨在检测地塞米松经皮外膜给药的安全性和可行性。成功介入后，沿0.014“导丝将外膜微输注导管推进至治疗节段。将其微针（0.9 mm长× 140 μm直径）部署到外膜中，以输送与造影剂（80：20比例）混合的地塞米松（DEX，4 mg/ml），提供荧光透视可视化。主要安全性结局指标是无血管夹层、血栓形成或外渗，而主要有效性结局是多普勒确定的二元再狭窄，定义为收缩期峰值流速比>2.5。20例Rutherford临床分类2-5的患者入组本研究。平均年龄为66岁，55%患有糖尿病。治疗的病变长度为8.9 ± 5.3 cm，50%为慢性完全闭塞。80%的治疗病变位于远端股浅动脉或腘动脉。所有病变均通过球囊血管成形术和临时支架植入术治疗（N=6），结果不理想。三名患者也接受了斑块切除术治疗。每厘米病变长度平均注射1.6 ± 1.1 mg（0.5 ± 0.3 mL）地塞米松磷酸钠。总的来说，每例患者平均注射12.1 ± 6.1 mg DEX。每个病变所需的平均注射次数为3.0 ± 1.3 cm，最少1次，最多6次。药物输送的技术成功率为100%，无手术或药物相关不良事件。平均Rutherford评分从术前的3.1 ± .7（中位数3.0）降至6个月时的.5 ± .7（中位数0.0），P<.00001。在同一时间间隔内，第一条腿ABI从0.68 ± 0.15增加到0.89 ± 0.19，P= 0.0003。本研究中的术前C反应蛋白为6.9 ± 8.5，表明基线炎症严重，术后24小时增加至14.0 ± 23.1 mg/l（增加103%）。然而，这种增加没有达到统计学显著性p= 0.14。2例患者通过在随访期间重新闭塞其治疗的索引病变节段达到了一期通畅率丧失的主要疗效终点。通过微输注导管进行外膜给药是股腘动脉段连续治疗中基于内膜的方法的安全可行的替代方法。6个月的初步结果表明，血管周围地塞米松治疗可以改善股动脉和腘动脉血管成形术后的结局，并支持对该方法进行进一步的临床研究。
Restenosis following endovascular treatment of the femoro-popliteal (fem-pop) segment is associated with the inflammatory response produced in the artery wall at the time of the procedure. While 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 fem-pop at the time of endovascular treatment would be safe, feasible and decrease the inflammatory response. 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 micro-infusion catheter was advanced over a 0.014″ wire to the treated segment. Its micro-needle (0.9 mm long × 140 μm diameter) was deployed into the adventitia to deliver dexamethasone (DEX, 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. 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 DEX was injected per patient. The mean number of injections required per lesion was 3.0 ± 1.3 cm, minimum 1 and maximum 6 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) pre-operatively to .5 ± .7 at 6 months (median 0.0), P<.00001. Over this same time interval the index leg ABI increased from .68 ± .15 to .89 ± .19, P=.0003. The pre-operative 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 p=.14. Two patients met the primary efficacy endpoint of loss of primary patency by re-occluding their treated segment of the index lesion during the follow up period. Adventitial drug delivery via a micro-infusion catheter is a safe and feasible alternative to intimal-based methods for adjunctive treatment in the femoro-popliteal 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 .
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影响因子：
37.8
作者：
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通讯作者：
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