Singapore INfra-Genicular Angioplasty With PAclitaxel-eluting Balloon for Critical Limb Ischaemia (SINGA-PACLI) Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 4
- 主要终点
- Primary patency of the treated (index) site at 6 months
研究概览
简要总结
Background
- In patients with critical limb ischaemia (CLI), the infragenicular arteries are often involved. Without revascularisation, amputation often is imperative. There is a high technical success rate of endovascular revascularisation of infragenicular arteries with percutaneous transluminal angioplasty (PTA), but mid- and long-term results are disappointing as restenosis frequently occurs. Drug-eluting balloon (DEB) PTA has been shown to improve patency rates after PTA of coronary arteries.
Aim
- To study the results of DEB-PTA compared to conventional balloon CB-PTA for the treatment of infragenicular lesions in patients with CLI.
- To evaluate cost-effectiveness of DEB-PTA versus CB-PTA in patients with critical limb ischemia (CLI) by quantifying the incremental cost-effectiveness ratio (ICER).
Hypothesis
- DEB PTA results in improved patency rates compared to CB-PTA for treatment of infragenicular arterial lesions in patients with CLI.
- DEB-PTA is a cost-effective strategy in patients with CLI compared with CB-PTA.
Methodology Multi-center, prospective, randomised parallel-group trial. Patients are eligible for enrolment if they have CLI and at least one infragenicular lesion with a maximal total lesion length of 20cm. Randomisation will be performed on a 1:1 ratio to either DEB-PTA or CB-PTA. Patients will be assessed prior and directly after the intervention, at 3, 6 and 12 months by Rutherford classification, ankle-brachial index, toe pressure and adverse events. Duplex will be performed at 3 months. Angiography will be performed before and directly after PTA and at 6 months. Primary end-point will be primary patency of the treated lesions at 6 months on angiography (defined as <50% stenosis, without re-intervention in the interim). Secondary end-points are limb salvage at 3, 6 and 12 months, primary patency of the treated lesion on Duplex at 3 months (defined as patency of the treated artery with peak systolic velocity (PSV) ≤2.0 m/sec), Rutherford classification, minor and major amputation, infrapopliteal endovascular re-intervention, patency of treated femoropopliteal sites (if applicable), infrapopliteal surgical bypass, peri-procedural complications and death at 3, 6 and 12 months.
A cost-effectiveness analysis (CEA) from a societal perspective will be performed in parallel with the randomized clinical trial with a 12-month time horizon.
详细描述
Methodology
- Study design:
This is an investigator-initiated multi-center, prospective, randomised, controlled, two-arm parallel-group study. The participating centers will be Singapore General Hospital and Tan Tock Seng Hospital.
Patients are eligible for enrolment if they have CLI and at least one infragenicular lesion with a maximal total lesion length of 20cm. Randomisation will be performed on a 1:1 ratio to either DEB PTA or CB PTA. Patients will be assessed prior and directly after the intervention, at 3, 6 and 12 months by Rutherford classification, ankle-brachial index, toe pressure and adverse events. Duplex will be performed at 3 months. Angiography will be performed before and directly after PTA and at 6 months. Primary end-point will be primary patency of the treated lesions at 6 months on angiography (defined as <50% stenosis, without re-intervention in the interim). Secondary end-points are limb salvage at 3, 6 and 12 months, primary patency of the treated lesion on Duplex at 3 months (defined as patency of the treated artery with peak systolic velocity (PSV) ≤2.0 m/sec), Rutherford classification, minor and major amputation, infrapopliteal endovascular re-intervention, patency of treated femoropopliteal sites (if applicable), infrapopliteal surgical bypass, peri-procedural complications and death at 3, 6 and 12 months.
A cost-effectiveness analysis will be performed alongside the 3-year randomized clinical trial of DEB PTA versus the CB- PTA. Both cost and utility outcomes will be determined from data sampled from the patient enrolled in the study and will be estimated using comparable time horizons. The time horizon of the economic analysis is 12 months, from the patient's study inclusion up to 12 months after PTA. Analysis will be performed from a societal perspective.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Age > 21 years
- •If female patient with child bearing potential, patient may not be pregnant at the study entry and must utilize reliable birth control for the duration of her participation into the study
- •Patient is willing and able to comply with the specified follow-up evaluation
- •Critical Limb Ischaemia, Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss) or 6 (major tissue loss)
- •Stenosis (>50% luminal loss) or occlusion of infra-genicular arteries (defined as: distal to the infra-popliteal artery), including the tibiofibular trunk, the anterior tibial artery, the posterior tibial artery and the peroneal artery
- •Infragenicular arterial lesions with length of <20cm
- •At least one crural (anterior tibial, posterior tibial or peroneal) artery with expected unobstructed runoff to ankle level after treatment
- •Successful guidewire crossing of the trial lesion
排除标准
- •Acute limb ischaemia
- •Subacute limb ischaemia which requires thrombolysis as first treatment modality
- •Previous major amputation of the affected limb (at or above the level of the ankle)
- •Concurrent iliac or femoropopliteal artery disease not suitable for endovascular or surgical revascularisation
- •Concurrent iliac or femoropopliteal artery occlusion of >10cm, even if suitable for surgical or endovascular revascularization
- •Patients without (expected) distal runoff to the index site
- •Revascularization involving the same site within 30 days prior to the index procedure or planned revascularization of the same limb within 30 days of the index procedure
- •Previous implanted stent at the index site
- •Life expectancy of less than 6 months
- •Factors making clinical follow-up very difficult or impossible
- •Known allergy to paclitaxel
- •Known allergy to contrast media
- •Patients on Warfarin or any other anti-coagulants
- •Known allergy to anti-platelet drugs (Aspirin/ Clopidogrel) (or) unable to tolerate dual anti-platelet drugs therapy
- •Active history of gastritis and other bleeding tendencies precluding use of dual anti-platelet therapy
- •Known heparin induced thrombocytopenia (HIT type 2)
- •Patient unable or unwilling to tolerate contrast media
- •eGFR less than 50 ml/min/1.73m2 unless patient is on dialysis.
- •If the patient has significant heart disease and Left Ventricular Ejection Fraction Percentage (LVEF%) is less than 35 %.
- •Either PT/PTT of >1.5 times the median of normal that cannot be corrected for the time of the procedure (or ) INR >1.6 that cannot be corrected for the time of the procedure
- •Thrombocytopenia of platelet count <50,000 /µL (50 X 109/L) which cannot be corrected for the time of the procedure
研究组 & 干预措施
CB-PTA arm
After successful crossing of the trial lesion, a conventional angioplasty balloon with a diameter matching the trial vessel is advanced over the guidewire and is inflated at the trial lesion site, according to the normal practice of the operator. Comparisons of pre- and post-angioplasty percentage stenosis will be made in the same angiographic projection(s).
干预措施: CB-PTA (Device)
DEB-PTA arm
After successful crossing of the trial lesion, angioplasty with a conventional angioplasty balloon is performed before DEB-PTA. This is because the paclitaxel coating may be scrapped off the balloon if the DEB is used to cross the trial lesion. A conventional angioplasty balloon with a diameter matching the trial vessel is advanced over the guidewire and is inflated at the trial lesion site, according to the normal practice of the operator. A DEB with a diameter matching the trial vessel and lesion length is then advanced over the 0.018 inch guidewire and inflated at the trial lesion site for 60 seconds. If the lesion length is longer than the length of the balloon, a second inflation with another DEB will be required. The maximal total lesion length of the treated lesions will not exceed 20cm. Comparisons of pre- and post-angioplasty percentage stenosis will be made in the same angiographic projection(s).
干预措施: CB-PTA (Device)
DEB-PTA arm
After successful crossing of the trial lesion, angioplasty with a conventional angioplasty balloon is performed before DEB-PTA. This is because the paclitaxel coating may be scrapped off the balloon if the DEB is used to cross the trial lesion. A conventional angioplasty balloon with a diameter matching the trial vessel is advanced over the guidewire and is inflated at the trial lesion site, according to the normal practice of the operator. A DEB with a diameter matching the trial vessel and lesion length is then advanced over the 0.018 inch guidewire and inflated at the trial lesion site for 60 seconds. If the lesion length is longer than the length of the balloon, a second inflation with another DEB will be required. The maximal total lesion length of the treated lesions will not exceed 20cm. Comparisons of pre- and post-angioplasty percentage stenosis will be made in the same angiographic projection(s).
干预措施: DEB-PTA (Device)
结局指标
主要结局
Primary patency of the treated (index) site at 6 months
时间窗: 6 months
Primary patency is defined as less than or equal 50% loss of luminal diameter at the treated site on angiography without re-intervention in the interim.
次要结局
- Limb-salvage rate(at 3, 6 and 12 months)
- Primary patency of the treated (index) site(at 3 months)
- Clinical categorisation of the treated ischemic leg(at 3, 6 and 12 months)
- Minor amputation(at 3, 6 and 12 months)
- Primary patency of treated femoropopliteal sites(From the date of randomization until the date of end of primary patency of treated femoropopliteal sites (asscessed up to 12 months))
- Infrapopliteal surgical bypass of the trial leg(at 3, 6 and 12 months)
- Infrapopliteal endovascular re-intervention of the trial leg(at 3, 6 and 12 months)
- Peri-procedural complications((within 30 days))
- Death(From the date of randomization until the date of death from any cause (asscessed up to 12 months))
- Incremental cost-effectiveness ratio (ICER)(at 3 month, 6 month and 12 month)