LIMBO-PTA: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.
研究概览
简要总结
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).
详细描述
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone sodium phosphate injection (4 mg/mL) after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients (60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10 control) at up to 30 sites in Europe and the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone in reducing inflammation and restenosis in patients with clinical evidence of chronic critical limb ischemia with an angiographically significant lesion in the infrapopliteal crural vessels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening Criteria:
- •Age ≥18 years
- •Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an IRB/EC approved consent form
- •Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
- •Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4, 5 or 6
- •Life expectancy >1 year in the Investigator's opinion
- •Angiographic Criteria:
- •Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound
- •Reference vessel(s) diameter ≥2 mm
- •Single or multiple atherosclerotic lesion ≥70% in at least one infrapopliteal crural target vessel including the tibioperoneal trunk that totals up to 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)
排除标准
- •Screening Criteria:
- •Patient unwilling or unlikely to comply with visit schedule
- •Planned major index limb amputation
- •Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
- •Inability to receive study medications
- •Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
- •Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature
- •Angiographic/Procedural Criteria:
- •Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries in which there is a failure to successfully treat and obtain a <30% residual stenosis
- •Index lesion length is >30 cm as measured from proximal normal vessel to distal normal vessel
- •Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-index lesions) >50 cm
- •Lesions revascularized during the index case but untreated by Bullfrog
- •Use of alternative therapy, e.g. atherectomy, laser, or radiation therapy, as part of the index lesion treatment, or use of any drug eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) for treatment of any infra-inguinal lesions during the study procedure or during the initial six-month follow up period
- •Previously implanted stent in the TL(s)
- •Aneurysm in the target vessel
- •Acute thrombus in the target limb
- •Failure to cross the TL with a guide wire; however, subintimal wire crossing is allowed
- •Heavy eccentric or concentric calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall
研究组 & 干预措施
Treatment Group: Dexamethasone Delivery
Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States.
Patients will be randomized 1:1 to receive either the active treatment or control therapy.
Treatment Group: Standard endovascular revascularization therapy consisting of angioplasty followed by Dexamethasondihydrogenphosphat-dinatrium (Ph.Eur.) 4 mg/mL Injektionslösung and with or without stent placement. The drug is diluted to 3.2 mg/mL and administered to the adventitia per Bullfrog Instructions for Use in a dose of 0.8 mg dexamethasone (0.25 mL) per cm of desired vessel treatment length, up to 30 cm.
干预措施: Dexamethasone sodium phosphate injection, USP, 4 mg/mL (Drug)
结局指标
主要结局
Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.
时间窗: Up to 6 months following the procedure
Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.
Freedom from CD-TLR
时间窗: Up to 6 months following the procedure
Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.
Freedom from MALE
时间窗: Up to 6 months following the procedure
Freedom from major adverse limb event (MALE) within 6 months.
TVAL% change from post-procedure
时间窗: 6 months following the procedure
Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any CD-TLR of the target lesion before 6 months.
次要结局
- Change in foot wounds versus baseline(30 days, 6 and 12 months post-procedure)
- Secondary sustained clinical improvement versus baseline(30 days, 6 and 12 months post-procedure)
- Walking capacity assessment versus baseline(30 days, 6 and 12 months post-procedure)
- Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.(Up to 12 months following the procedure)
- QVA change from post-procedure(6 months following the procedure)
- SAE/MALE assessment(30 days, 6 and 12 months post-procedure)
- IVUS change from post-procedure(6 months following the procedure)
- EQ5D versus baseline(30 days, 6 and 12 months post-procedure)
- CD-TLR(30 days, 6 and 12 months post-procedure)
- Infusion technical success(Intra-procedural)
- Event-free survival(12 months following the procedure)
- Amputation-free survival(30 days, 6 and 12 months post-procedure)
- Major and minor amputations and amputation level(30 days, 6 and 12 months post-procedure)
- Resolved CLI death(30 days, 6 and 12 months post-procedure)
- Primary sustained clinical improvement versus baseline(30 days, 6 and 12 months post-procedure)
- SVS WIfI score versus baseline(30 days, 6 and 12 months post-procedure)
- Inflammatory biomarker changes from baseline(24 hours and 30 days)
- Revascularization success(Intra-procedural)
- Healthcare economic analysis(From baseline to 24 months)