TANGO: Temsirolimus Adventitial Delivery to Improve ANGiographic Outcomes Below the Knee
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Freedom from MALE-POD
研究概览
简要总结
This is a prospective, multi-center, randomized, dose escalation study to document the effects of adventitial delivery of temsirolimus (Torisel) after revascularization of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).
详细描述
This is a prospective, multi-center, randomized, dose escalation study to document the effects of adventitial delivery of temsirolimus (Torisel) after revascularization of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 60 patients (20 low-dose, 20 high-dose and 20 control) at up to 15 sites in the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of temsirolimus in reducing intimal hyperplasia, inflammatory markers and composite safety endpoints in patients with clinical evidence of chronic critical limb ischemia after revascularization of one or more angiographically significant lesion(s) in below-knee popliteal or tibial 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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening Criteria:
- •Age ≥18 years and <90 years
- •Patient has been informed of the nature of the study, agrees to participate and has signed an IRB approved consent form
- •Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a highly effective method of birth control (See Section 12.2) one month preceding and 12 months following study treatment
- •Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the distal segment (P3) of the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 3, 4 or 5
- •Life expectancy >1 year in the Investigator's opinion
- •Angiographic Criteria:
- •Target vessel(s) diameter ≥2 mm and ≤8 mm
- •Single or multiple atherosclerotic lesion(s) ≥70% in at least one below-knee popliteal or tibial target vessel including the tibioperoneal trunk that totals up to no greater than 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)
- •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, if a wound is present at baseline
排除标准
- •Screening Criteria
- •Patient is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint
- •Patient unwilling or unlikely to comply with visit schedule
- •Patients who are incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial
- •Patient is already receiving or planned to receive systemic immunotherapy, chemotherapy, or steroids (however, inhaled steroids for asthma treatment or topical steroid uses are allowed)
- •Patient has a bilirubin level of >1.5xULN
- •Recent (<30 days prior to study procedure) myocardial infarction
- •Cerebrovascular accident <60 days prior to the study procedure
- •Planned major (above the ankle) target limb amputation
- •Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers (<25mm) are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
- •Inability to receive temsirolimus or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions Estimated glomerular filtration rate (eGFR, calculated from serum creatinine using an isotope dilution mass spectrometry (IDMS)-traceable equation) 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 or non-ischemic in origin
- •Angiographic/Procedural Criteria
- •Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries (P1 and P2) in which there is failure to successfully treat and obtain a <30% residual stenosis post-revascularization, with bailout stenting as needed (in-flow lesions should be treated prior to treating the target lesion)
- •Target 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-target lesions) >30 cm
- •Use of alternative therapy, e.g. radiation therapy, drug-eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) as part of the target lesion treatment or during the previous 2 months within the target lesion
- •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 target 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
Active Comparator: Temsirolimus Delivery High Dose
High-Dose Group: 0.4 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
干预措施: Temsirolimus (Drug)
Active Comparator: Temsirolimus Delivery Low Dose
Low-Dose Group: 0.1 mg/mL temsirolimus (including 20% contrast) Patients qualifying for enrollment will be randomized 2:1 for inclusion in either the treatment (low-dose or high-dose) or the control group. The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
干预措施: Temsirolimus (Drug)
Placebo Comparator: Saline Delivery
Control Group: Saline/contrast (80% normal saline for injection:20% non-ionic contrast) The first 20 patients randomized to treatment will receive low-dose. After the first 30 patients (20 low-dose and 10 control) are enrolled in the trial, enrollment will be held until 30-day safety endpoints are met, at which point the dosage will be escalated to the high dose and the trial will resume, with the remaining 30 patients randomized 2:1 for high-dose or control.
干预措施: Saline (Drug)
结局指标
主要结局
Freedom from MALE-POD
时间窗: Up to 30 days post-procedure
Freedome from MALE-POD at 30 days.
Transverse-view vessel area loss percentage (TVAL%) of the target lesion
时间窗: Within 6 months post-procedure
Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any TLR of the target lesion before 6 months.
次要结局
- Freedom from a composite of all-cause death, MALE and unplanned minor amputation in target limb(Up to 30 days post-procedure)
- Freedom from Serious Adverse Events (SAEs)(Up to 12 months post-procedure)
- Event-free survival(Up to 12 months post-procedure)
- Improvement in % diameter stenosis and maximum late lumen loss (LLL) of the target lesion(Up to 6 months post-procedure)
- Improvement in luminal volume by intravascular ultrasound (IVUS)(Up to 6 months post-procedure)
- Composite of major amputation, target vessel occlusion or CD-TLR(Up to 12 months post-procedure)
- Freedom from a composite of death, unplanned minor amputation, clinically driven TLR, and major adverse limb events (MALE)(Up to 12 months post-procedure)