LIMBO-ATX: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 10
- 主要终点
- Freedom from MALE
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 atherectomy-based revascularizations 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 after atherectomy-based revascularizations 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 the United States and Europe. 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 failure to successfully treat and obtain a <30% residual stenosis
- •Target lesion length is >25 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-target lesions) >25 cm
- •Lesions revascularized during the index case but untreated by Bullfrog
- •Use of alternative therapy, e.g. 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
Dexamethasone Delivery
Up to 60 atherectomy-based revascularization procedures at up to 30 sites in the United States and Europe.
For Subjects randomized into the Dexamethasone Delivery arm, this protocol will utilize a 4 mg/mL preparation of Dexamethasone Sodium Phosphate Injection, USP. Each milliliter of the solution contains 4.37 mg of dexamethasone sodium phosphate equivalent to 4 mg of dexamethasone phosphate or 3.33 mg of dexamethasone. The total dose of Dexamethasone Sodium Phosphate Injection, USP will be diluted by 20% prior to infusion. This will result in a final concentration of 3.2 mg dexamethasone phosphate (3.5 mg dexamethasone sodium phosphate, or 2.67 mg dexamethasone) in each milliliter of solution.
干预措施: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL (Drug)
结局指标
主要结局
Freedom from MALE
时间窗: Up to 6 Months following the procedure
Freedom from major adverse limb event (MALE) within 6 months.
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.
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
- QVA change from post-procedure(6 months following the procedure)
- SVS WIfI score versus baseline(30 days, 6 and 12 months following the 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)
- Primary sustained clinical improvement versus baseline(30 days, 6 and 12 months following the procedure)
- Walking capacity assessment versus baseline(30 days, 6 and 12 months following the procedure)
- Inflammatory biomarker changes from baseline(24 hours and 30 days)
- Infustion technical success(Intra-procedural)
- Revascularization success(Intra-procedural)
- Event-free survival(12 months following the procedure)
- IVUS change from post-procedure(6 months following the procedure)
- Change in foot wounds versus baseline(30 days, 6 and 12 Months following the procedure)
- Resolved CLI death(30 days, 6 and 12 months following the procedure)
- CD-TLR(30 days, 6 and 12 months following the procedure)
- Secondary sustained clinical improvement versus baseline(30 days, 6 and 12 months following the procedure)
- EQ5D versus baseline(30 days, 6 and 12 months following the procedure)
- SAE/MALE assessment(30 days, 6 and 12 months following the procedure)
- Healthcare economic analysis(From baseline to 24 months)
- Amputation-free survival(30 days, 6 and 12 months following the procedure)
- Major and minor amputations and amputation level(30 days, 6 and 12 months following the procedure)