Colchicine in Chronic Limb-Threatening Ischemia for Reduction of Complications and Limb Events in Asia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 5
- 主要终点
- Amputation-free survival
研究概览
简要总结
Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease, a condition in which narrowed or blocked arteries reduce blood flow to the legs. People with CLTI may have severe leg pain at rest, non-healing wounds, or gangrene, and face a high risk of leg amputation and death. Even after successful procedures to restore blood flow to the leg (called revascularization), many patients still experience serious complications. Inflammation in the blood vessels is believed to play an important role in these poor outcomes.
Colchicine is an anti-inflammatory medication that has been used safely for decades to treat gout and other inflammatory conditions. Recent large clinical trials have shown that a low dose of colchicine (0.5 mg per day) can reduce heart attacks and strokes in patients with coronary artery disease. However, it has not been studied in patients with CLTI.
The CIRCLE-Asia trial (Colchicine in Chronic Limb-Threatening Ischemia for Reduction of Complications and Limb Events in Asia) is a pilot study designed to evaluate whether colchicine can improve outcomes in patients with CLTI who have recently undergone a successful procedure to restore blood flow to their leg. Treatment begins within 7 days of the procedure.
This is a randomized, double-blind, placebo-controlled, multicenter trial conducted at five hospitals in Taiwan. A total of 200 adult patients with CLTI who have undergone successful revascularization will be randomly assigned in a 1:1 ratio to receive either colchicine 0.5 mg once daily or a matching placebo pill, in addition to their usual medications, for 12 months. Neither the patients nor the study doctors will know which treatment each patient receives.
The main outcome of interest is amputation-free survival, defined as the time until major amputation of the affected leg (above the ankle) or death from any cause, over 12 months of follow-up. The study will also assess other important outcomes including major limb complications, heart attacks, strokes, wound healing, changes in blood flow measurements, inflammatory blood markers, quality of life, and medication safety.
This pilot trial will provide the first randomized evidence on the potential benefits and safety of colchicine in CLTI patients and will help inform the design of a larger definitive trial.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years.
- •Documented chronic limb-threatening ischemia, meeting the following:
- •Presence of ischemic symptoms compatible with CLTI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain consistent with Rutherford classes 4-5 AND
- •Imaging evidence within the past 12 months showing atherosclerotic PAD, including CTA, MRA, angiography or duplex ultrasound AND
- •Ankle-Brachial Index (ABI) ≤0.80 or Toe-Brachial Index (TBI) ≤0.60 for patients without prior revascularization; ABI ≤0.85 or TBI ≤0.65 for those with prior revascularization OR
- •Ischemic rest pain alone (Rutherford class 4) defined as ankle systolic pressure <50 mmHg, toe pressure of <30 mmHg, transcutaneous PO2 of <30 mmHg, or flat-line transtarsal pulse volume recording OR
- •Tissue loss with or without ischemic rest pain (Rutherford class 5) defined as ankle systolic pressure <70 mmHg, toe pressure of <50 mmHg, transcutaneous PO2 of <30 mmHg, or flatline transtarsal pulse volume recording
- •Recent successful revascularization:
- •Underwent technically successful endovascular therapy (EVT) or surgical bypass within the last 7 days prior to randomization
- •For individuals requiring multiple revascularization attempts on the same index leg, the procedure considered for eligibility (in other words, the qualifying or index procedure) must be the final planned or anticipated revascularization attempt
- •There must be demonstrated graft or vascular patency after the qualifying revascularization procedure with one in-line blood flow to the foot, either by angiography, duplex ultrasound, CTA or MRA
- •There must be no immediate plan for reintervention
- •Informed Consent:
- •Demonstrated ability and willingness to adhere to the study protocol, attend scheduled follow-up visits, complete all required assessments, and provide written informed consent
排除标准
- •Age <18 years
- •Asymptomatic or mild disease: Patients who underwent revascularization for disease graded Rutherford classes 0-3
- •Patients with major tissue loss (Rutherford 6) in whom major amputation was planned at the time of screening
- •Failure to establish at least one tibial artery outflow after revascularization
- •Recent acute limb ischemia events within 2 weeks of screening
- •Clinical signs of active, uncontrolled, severe limb infection or septicemia, such as fever exceeding 38.5°C, a white blood cell count above 15,000 cells/µL, or hypotension, at the time of screening (this does not include osteomyelitis confined to the phalanges or metatarsal heads or foot cellulitis treatable with IV antibiotics at the time of revascularization)
- •Unstable hemodynamics after the index revascularization procedure
- •Unable to tolerate any antiplatelet agent or with severe bleeding diathesis
- •Acute coronary syndrome, acute stroke, or hospitalization for heart failure within 30 days of screening
- •Any contraindication or known intolerance to colchicine
- •Requirement for colchicine for another indication
- •Need for use of medications known to have drug-drug interactions with colchicine, particularly drugs known to inhibit CYP3A4 or P-glycoprotein
- •Active hepatitis or severe liver cirrhosis (Child Pugh C)
- •Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception
- •Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s)
- •Life expectancy <1 year
研究组 & 干预措施
Colchicine
Colchicine 0.5 mg per tab, taken 1 tab daily
干预措施: Colchicine 0.5 MG Oral Tablet Once Daily (Drug)
Placebo
Placebo tablets matching in appearance with study drug, taken 1 tab per day
干预措施: Placebo (Drug)
结局指标
主要结局
Amputation-free survival
时间窗: 12 months
Defined as the time to major (above the ankle) amputation of the study limb or death from any cause
次要结局
- Number of Participants with Major (Above the Ankle) Non-Traumatic Amputation of the Study Limb(12 months)
- Major adverse limb event (MALE, including non-traumatic above-ankle amputation and major lower limb artery reintervention) and its components(12 months)
- Major adverse cardiovascular event (MACE, including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) and its components(12 months)
- Wound healing rates at 3, 6, 9 and 12 months for Rutherford 5 patients (or time to wound healing)(12 months)
- Number of Participants with Acute Limb Ischemia(12 months)
- Number of Deaths from Any Cause(12 months)
- Number of Deaths from Cardiovascular Causes(12 months)
- Number of Deaths from Limb-Related Causes(12 months)
- Number of Participants with Adverse Gastrointestinal Events(12 months)
- Number of Participants with Adverse Hematologic Events(12 months)
- Number of Participants with Serious Infections(12 months)
- Number of Participants with Diarrhea(12 months)
- Number of Participants with Drug Discontinuation Due to Any Adverse Event(12 months)
- Change in Health-Related Quality of Life as Measured by the EQ-5D-5L Index Score(Baseline and 12 months)
- Change in Disease-Specific Quality of Life as Measured by the VASCUQOL-6 Score(Baseline and 12 months)
- Change in Walking Ability as Measured by the Walking Impairment Questionnaire (WIQ) Score(Baseline and 12 months)
- Change in Ankle-Brachial Index (ABI)(Baseline and 12 months)
- Change in Toe-Brachial Index (TBI)(Baseline and 12 months)
- Change in Transcutaneous Oxygen Pressure (TcPO2)(Baseline and 12 months)
研究者
Donna Shu-Han Lin
Dr
Shin Kong Wu Ho-Su Memorial Hospital