Chronic Limb-Threatening Ischemia

ORACLE is a Europe-wide study that will follow 250 people with critical limb-threatening ischemia (CLTI). It aims to see how well orbital atherectomy (OA) works in real-life practice. OA is a procedure that uses a tiny spinning tool to gently remove hard calcium from inside an artery, helping to open the vessel so other treatments-like balloons or stents-can work better. The study focuses on people who have heavily calcified arteries in the femoropopliteal or infrapopliteal areas of the leg.

RESCUE is a Europe-wide study that will follow 400 people with critical limb-threatening ischemia (CLTI). It aims to see how well Esprit BTK™ Everolimus Eluting Resorbable Scaffolds work in real-life medical settings. The study focuses on people who have heavily calcified arteries in the infrapopliteal areas of the leg. These drug-eluting resorbable scaffolds release a medication that helps prevent the inner wall of the blood vessel from thickening after injury or surgery. This can reduce the chance of the artery becoming blocked again (a problem called restenosis), while also giving temporary structural support to the vessel. Over time, the scaffold naturally dissolves in the body, which may lower the long-term risks associated with permanent metal stents.

Chronic limb threatening ischemia (CLTI) represents the most advanced stage of peripheral arterial disease (PAD) and is characterized by ischemic rest pain, non-healing wounds, or ischemic gangrene. High-risk PAD populations including patients with end-stage renal disease and or diabetes also experience worse outcomes with significantly increased rates of amputation and mortality. Although some patients with PAD are best treated with a combination of medical management, exercise and lifestyle modification, revascularization is indicated in those with advanced stages of disease and particularly in the presence of CLTI. Revascularization of below-the-knee (BTK) arteries is required for most patients suffering from CLTI, but treatment faces numerous challenges comprising calcification, small vessel size, long-lesion length and early elastic recoil. With regard to these challenges, numerous innovative techniques and devices have been developed within the past decades to optimize endovascular treatment of BTK vessels. The Spur Peripheral Retrievable Scaffold System (Spur) was developed to directly address many of these pitfalls of infrapopliteal arterial disease. The premise of the design of the Spur is to provide temporary mechanical scaffolding and to prepare the vessel for treatment with a drug-coated balloon (DCB) to enhance drug absorption by creating channels in the endothelium by the deployed Spur. The objective of this study is to perform a prospective, single-center, single-arm, non-randomized study to evaluate acute vessel recoil following BTK treatment with the Spur Retrievable Scaffold System in combination with a commercially available DCB in specific patients populations. Specific patient populations that are selected to participate in this study are either at high risk to discover unfavorable outcomes with standard techniques due to a high complexity of lesions and/or patients that are not adequately mirrored in available studies. The patient cohorts that will be studied are diabetics and patients on hemodialysis (for at least 6 months). As women are commonly under-represented in comparable trials, this study requires at least 50% of women for each cohort. The primary endpoint is vessel recoil within 15 minutes post treatment assessed with angiography. Secondary endpoints will be followed out to 12 months.

Peripheral arterial disease involving the iliac arteries is a common manifestation of systemic atherosclerosis and a major cause of lifestyle-limiting claudication and chronic limb-threatening ischemia. Endovascular iliac artery stenting has become the preferred treatment strategy for most iliac lesions, including complex TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions, owing to high technical success rates and lower perioperative morbidity compared with open surgical reconstruction. Despite widespread adoption of endovascular treatment, available evidence regarding predictors of major adverse limb events (MALE) after iliac artery stenting remains limited, particularly in unselected real-world populations with substantial comorbidity burden. Patient-related factors, including frailty, may contribute to post-procedural outcomes in addition to lesion-related characteristics. This retrospective single-center cohort study will evaluate clinical outcomes following endovascular iliac artery stenting in consecutive adult patients treated at IRCCS Galeazzi-Sant'Ambrogio Hospital, Milan, Italy. The study will assess the occurrence of major adverse limb events (MALE), primary patency, peri-procedural complications, target lesion revascularization, restenosis or occlusion, and all-cause mortality. Clinical, anatomical, and procedural factors associated with adverse limb outcomes, including frailty assessed by the modified five-item Frailty Index (mFI-5), will also be investigated.

The objective of this study is to assess whether efficacy of the AcoArt Litos PCB is superior and whether safety of AcoArt Litos PCB is noninferior to the control device (FDA cleared PTA Balloon Catheter) regarding treatment of obstructions in the infrapopliteal arteries (located distal to the P3 segment of the popliteal artery and extending to the tibiotalar joint) in patients presenting with chronic limb-threatening ischemia (CLTI)(Rutherford 4-5)

The purpose of this study is to determine if IVUS use, as compared to angiography alone, prevent major adverse limb events (MALE) or binary restenosis (a greater than 50% re-narrowing of the treated artery) in adult patients who have CLTI and are undergoing percutaneous revascularization.

CALCIO is a multicentre, prospective, observational cohort study that will collect real world data on the use of intravascular Lithotripsy (IVL) with the Shockwave IVL system to disrupt calcified femoropopliteal and crural lesions in patients with chronic limb-threatening ischemia (CLTI). The primary objective of CALCIO is to understand the effectiveness of IVL in promoting wound healing and preventing amputation. The secondary objectives of CALCIO are to evaluate the immediate effectiveness of the treatment in restoring vessel patency as well as its safety and impact on patients' quality of life.

A prospective, single-arm, multi-center study designed to gather additional information on the LimFlow System.

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.

The goal of this study is to learn if a new medicine (called antiplatelet and anticoagulant \[APAC\]) can help the body to prevent blood clots and whether APAC is safe and well tolerated in patients with blocked or narrowed arteries in their legs (peripheral arterial occlusive disease \[PAOD\]), and in patients with severely restricted poor blood flow to the legs that threatens limb health (chronic limb-threatening ischemia \[CTLI\]). The study also aims to find the best dose of the medicine. The study consists of two parts: Part A will include patients with PAOD and CTLI, Part B will only include patients with CTLI who are having a procedure to restore blood flow in their legs. Both parts will be subdivided into two subgroups (A1 and A2, B1 and B2) which will test different APAC doses and compare single dosing to weekly dosing for 4 weeks. APAC is injected into the blood. The possible treatment response will be compared either to a placebo (a look-alike substance that contains no drug), or to the current standard treatment. Patients will participate in the study for up to 90 or 180 days. During this time, patients will be regularly examined and asked to answer questions concerning their quality of life.

Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease and remains a major health problem. Although the angiosome concept was introduced to guide revascularization by restoring direct blood flow to the affected tissue, its usefulness is limited by anatomical variations, collateral circulation, and wounds involving multiple territories. The emerging "woundsome" concept focuses instead on improving arterial perfusion directly to the wound area, recognizing that both direct revascularization and

This study is a multicenter observational study designed to evaluate the the effectiveness and safety of drug-coated balloon (DCB) angioplasty for below the knee arterial lesions in patients critical with Limb Threatening Ischemia (CLTI).

The goal of this observational study is to characterise the relationships between inflammation, microcalcification and thrombus activity in atherosclerotic plaques in peripheral and systemic vascular territories in patients with symptomatic peripheral arterial disease.

The objective of this prospective, single-blinded, randomized controlled trial is to evaluate the safety and efficacy of the MAGNITUDE BRS System for the planned treatment of narrowed infrapopliteal lesions. Approximately 276 subjects will be randomized in a 1:1 ratio. The clinical investigation will be conducted at up to 60 clinical sites globally.

The goal of this observational study is to learn whether activation of the GLP-1 receptor could represent a therapeutic target by characterizing its expression and associated inflammatory mechanisms in patients with peripheral artery disease, according to disease severity, in adults with symptomatic lower-limb peripheral arterial disease. The main questions it aims to answer are: * Is the level of GLP-1 receptor (GLP1R) expression on peripheral blood mononuclear cells (PBMC) different between patients with intermittent claudication (ischemia of effort) and those with chronic limb-threatening ischemia? * Is GLP1R expression associated with inflammatory and oxidative profiles of PBMC? * Can GLP-1 receptor agonists reverse inflammatory and oxidative alterations induced by plasma from patients with peripheral artery disease in endothelial cell cultures? * Are there specific plasma proteomic signatures associated with GLP1R overexpression? Researchers will compare patients with intermittent claudication to patients with chronic limb-threatening ischemia to see if disease severity is associated with differences in GLP1R expression, PBMC inflammatory/oxidative phenotype, and plasma proteomic profiles. Participants will: * Provide an additional blood sample (15 mL) collected during a routine, clinically indicated blood draw * Have PBMC isolated for measurement of GLP1R expression and assessment of inflammatory and oxidative markers * Have plasma analyzed for proteomic profiling and used in in-vitro endothelial cell experiments Participation ends after completion of the blood sampling, and no additional procedures beyond standard clinical care are required.

Lower limb circulatory insufficiency and the associated chronic wounds are common health problems among the elderly. These issues not only affect the individual's mobility and quality of life but also potentially increase medical costs and caregiving expenses. Traditional treatment methods often employ medications to enhance blood circulation, but these clinical approaches have limited effectiveness and induce the risk of side effects. Utilizing exercise as an intervention strategy can help improve lower limb blood circulation in the elderly while reducing the side effects associated with medications. However, due to physical frailty, elderly individuals often cannot participate in high-intensity exercises to improve their circulatory performance. Therefore, this study will develop a lower limb circulation enhancement exercise system to improve the circulatory performance in individuals with poor lower limb circulation. It will compare the effects of lower limb circulation enhancement exercise, vibration exercise, and mixed exercise on improving blood circulation and functional performance in the elderly or individuals with poor lower limb circulation. Participants will be randomly assigned into three groups: the lower limb circulation enhancement exercise group, the vibration exercise group, and the mixed exercise group. In addition, a separate group of young adults (control group) will serve as a reference for baseline comparisons. Initially, all participants will undergo a one-time exercise test, followed by a 12-week intervention. The lower limb circulation enhancement exercise group will perform a 30-minute leg press rowing exercise three times a week, while the vibration exercise group will engage in vibration exercise at the same frequency, and the mixed exercise group will perform group-based mixed exercise training at the same frequency. The young adult control group will not receive any intervention but will undergo the same assessments. Outcome evaluations before and after the intervention include lower limb blood perfusion monitoring, pain scales, and functional performance assessments.

"• A prospective, single-center randomized controlled comparison trial. * A total of 100 patients with symptoms of chronic limb-threatening ischemia (Rutherford category 5) undergoing endovascular treatment for anterior tibial artery or posterior tibial artery lesions will be included if they meet the inclusion criteria and do not meet any exclusion criteria. * Patients will be randomized in a 1:1 open-label manner either to the pressure wire-guided group or the angiography-guided group. * Patients will be treated with balloon angioplasty for anetrior tibial artery or posterior tibial artery lesions. * In the angiography-guided group, balloon angioplasty will be performed to achieve an optimal procedural result, as determined by angiography. Optimal results are defined as antegrade blood flow without residual stenosis \>50% or flow-limiting dissection. * In the Pressure Wire-guided gorup, balloon angioplasty will be performed to obtain optimal procedural result based on both angiography and a pressure gradient over the target lesion. Optimal pressure gradient is less than 10 mmHg by measurement using a Pressure Wire. * The primary efficacy endpoint is defined by attaiment of skin perfusion pressure ≥50 mmHg within 1-3 days after the index procedure. * Patients will be followed at 1, 3, and 6 months after the procdure to assess wound healing status, and clinical events."

The goal of the study is to identify and validate flow measurement and ultrasound images in patients undergoing vein bypass surgery below-knee and above ankle

Chronic limb-threatening ischemia (CLTI) represents the most advanced stage of peripheral artery disease (PAD), characterized by rest pain, non-healing ulcers, or gangrene, and is associated with high morbidity and risk of amputation if left untreated. Infra-popliteal arteries are frequently involved in CLTI, especially in diabetic and elderly patients, posing significant challenges due to diffuse, calcified, and long-segment occlusive lesions. Conventional balloon angioplasty remains a first-line endovascular treatment but is limited by high restenosis and vessel recoil rates. Atherectomy, a plaque debulking technique, aims to improve luminal gain and vessel compliance prior to angioplasty, potentially enhancing outcomes in heavily calcified lesions. The combination of atherectomy and balloon angioplasty has shown promise in reducing dissection rates and improving technical success, yet its superiority over conventional angioplasty alone remains controversial. Given the growing use of endovascular therapies, a comparative analysis of outcomes between combined atherectomy-balloon angioplasty and conventional angioplasty in infra-popliteal interventions is essential to guide evidence-based management in CLTI patients.

This interventional prospective study aims to assess the effectiveness of single vessel versus multiple vessel infrapopliteal angioplasty in patients with chronic threatening limb ischemia . The study compares limb salvage rates and clinical outcomes across two groups over a defined follow up period

In recent years, mobile health (mHealth) apps have promised improved monitoring of health conditions to improve clinical outcomes. The objective of this study is to conduct a pilot randomized clinical trial (RCT) to evaluate the impact of using remotely collected patient generated health data (PGHD) from older patients undergoing bypass surgery due to chronic limb threatening ischemia. The hypothesis is that integrating PGHD with an EHR system will help providers manage post-surgical symptoms and thus improve post-operative mobility and quality of life health outcomes.

This is a prospective, multicenter, observational study designed to evaluate the clinical outcomes of the Ranger™ SL paclitaxel-coated balloon, a type of drug-coated balloon (DCB), in the treatment of below-the-knee (BTK) lesions in patients with chronic limb-threatening ischemia (CLTI) in China. All enrolled patients will be followed for six months. Patients diagnosed with CLTI who undergo treatment with the Ranger DCB will be included in the study. The primary outcome is the incidence of major adverse events (MAEs).

The aim of this clinical study is to 1) establish a healthy database for nuclear perfusion imaging of the lower extremities and 2) assess the prognostic value of radiotracer-based perfusion imaging for predicting clinical outcomes in patients with peripheral artery disease (PAD) who are undergoing lower extremity revascularization procedures. We hypothesize that radiotracer imaging of the lower extremities will provide a sensitive non-invasive imaging tool for quantifying regional abnormalities in skeletal muscle perfusion and evaluating responses to medical treatment.

There is a lack of prospective observational studies of shockwave balloons in the treatment of moderate-to-severe calcification of the femoral popliteal artery at the international level. Therefore, in this study, we wish to set up a real-world study of shockwave balloon in the treatment of moderate-to-severe calcification to investigate the real-world efficacy of shockwave balloon in the treatment of moderate-to-severe calcified lesions.

Assessment of a novel diagnostic method for screening and diagnosing chronic limb-threatening ischemia (CLTI). Using hyperspectral and thermal imaging, the perfusion and oxygenation in the lower limbs will be studied in healthy and unhealthy individuals.