Chronic Limb-Threatening Ischemia
Conditions
Keywords
IMAGE-BTK, Chronic limb-threatening ischemia, Peripheral artery disease, Endovascular therapy, Intravascular ultrasound, Primary patency
Brief summary
Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease in which very poor blood flow in the arteries below the knee can cause rest pain, non-healing wounds, and even loss of the limb. It is often treated with endovascular therapy (EVT), a minimally invasive procedure that opens the blocked artery, but the artery frequently narrows or closes again afterward. These procedures are usually guided by X-ray pictures taken with dye (angiography). Intravascular ultrasound (IVUS) is an imaging tool that uses a small catheter inside the artery to give a more detailed view of the vessel, which may help doctors open it more completely. It is not yet clear whether adding IVUS improves results below the knee. This study is testing whether guiding treatment with IVUS plus angiography keeps the artery open better than angiography alone. Adults aged 18 or older with CLTI who are having endovascular therapy for a blocked artery below the knee may take part. Participants are assigned by chance to be treated with either both imaging methods or angiography alone, and are followed for 12 months. The main question is how well the treated artery stays open at 6 months; researchers will also compare repeat procedures, amputation, complications, wound healing, survival, and quality of life.
Interventions
PROCEDUREIntravascular ultrasound-guided EVT
Endovascular therapy of the below-the-knee artery is guided by intravascular ultrasound (IVUS) imaging in addition to X-ray angiography, with IVUS used to assess the lesion, size and select devices, optimize treatment, and confirm the final result.
PROCEDUREAngiography-guided EVT
Endovascular therapy of the below-the-knee artery is guided by X-ray angiography with contrast dye alone, without the use of intravascular ultrasound, to assess the lesion, size and select devices, and judge the final result.
Sponsors
Shin Kong Wu Ho-Su Memorial Hospital
National Taiwan University Hospital
Chi Mei Medical Hospital
Chang Gung Memorial Hospital
Taipei Veterans General Hospital, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Documented chronic limb-threatening ischemia, meeting the following criteria according to guidelines(13): * 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 who never underwent revascularization; ABI ≤0.85 or TBI ≤0.65 for those with history of prior revascularization procedures OR * Ischemic rest pain alone (Rutherford class 4) with 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) with ankle systolic pressure \<70 mmHg, toe pressure of \<50 mmHg, transcutaneous PO2 of \<30 mmHg, or flatline transtarsal pulse volume recording 3. Absence of occlusive upstream disease, defined by the following: * Demonstrated vascular patency from the aorta to the second segment of the popliteal artery (P2), either by angiography, duplex ultrasound, CTA or MRA within the last 7 days prior to randomization * In patients who underwent prior treatment for upstream disease, there are no restrictions in treatment modalities received as long as patency is demonstrated as previously defined * If upstream disease is planned to be treated in the same index procedure, technically successful treatment of the upstream vessels must be achieved before randomization, defined as less than 30% residual stenosis and no flow-limiting dissections 4. Informed Consent: * Demonstrated ability and willingness to adhere to the study protocol and provide written informed consent
Exclusion criteria
1. Age \<18 years 2. Asymptomatic or mild disease: patients who underwent revascularization for disease graded Rutherford classes 0-3 3. Patients with major tissue loss (Rutherford 6) in whom major amputation was planned at the time of screening 4. Patient with a history of prior major (above-the-ankle) amputation of the study limb 5. Unable to tolerate any antiplatelet agent or with severe bleeding diathesis 6. Clinical signs of active, uncontrolled, severe limb infection or septicemia, defined 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) 7. Acute coronary syndrome or acute stroke within 30 days of screening 8. Active hepatitis or severe liver cirrhosis (Child Pugh C) 9. Advanced CKD (defined with eGFR\<30 mL/min/1.73m2) or end-stage renal disease 10. Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception 11. Previous (within 30 days) or concomitant participation in another clinical study with investigational medicinal product(s) that has not yet reached its primary endpoint 12. Life expectancy \<1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary patency at 6 months | 6 months after the index procedure | Freedom from clinically driven target lesion revascularization (CD-TLR), total occlusion of the target vessel, or binary restenosis of the target lesion. Binary restenosis is defined as a peak systolic velocity ratio \>2.0 on duplex ultrasound. Reported as the proportion of participants meeting all three criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major amputation of the study limb | 12 months | Proportion of participants undergoing major (above-the-ankle) amputation of the study limb. |
| Major adverse limb events (MALE) | 12 months | Proportion of participants with a major adverse limb event, defined as a composite of above-ankle amputation of the study limb, CD-TLR, or all-cause mortality. |
| Composite freedom from limb events | 12 months | Proportion of participants free from all of the following: major amputation of the study limb, total occlusion of the target vessel, CD-TLR, and binary restenosis of the target lesion (peak systolic velocity ratio \>2.0 on duplex ultrasound). |
| Wound healing (Rutherford class 5 participants) | 1, 3, 6, 9, and 12 months | Wound healing rate, reported as the proportion of Rutherford class 5 participants with complete healing of the index wound. |
| Time to complete wound healing (Rutherford class 5 participants) | From the index procedure to 12 months | Time to complete wound healing, reported as the time since the index procedure to complete healing of the index wound in Rutherford class 5 participants. |
| Major adverse cardiovascular events (MACE) | 12 months | Proportion of participants with a major adverse cardiovascular event, defined as a composite of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death, and each component reported individually. |
| Acute limb ischemia | 12 months | Proportion of participants with an acute limb ischemia event in the study limb. |
| Limb-related mortality | 12 months | Proportion of participants who die from a limb-related cause. |
| All-cause mortality | 12 months | Proportion of participants who die from any cause. |
| Periprocedural complications | During the index procedure through 30 days | Proportion of participants with any periprocedural complication (e.g., dissection, perforation, distal embolization, access-site complication, or contrast-related event) related to the index procedure. |
| Disagreement in imaging findings between angiography and IVUS | During the index procedure (Day 0) | Proportion of treated lesions in which intravascular ultrasound (IVUS) findings differ from angiographic findings, as assessed by the core laboratory (including differences in vessel diameter, lesion length, degree of stenosis, plaque or calcium characterization, or identification of dissection or under-expansion). |
| Procedural success | During the index procedure (Day 0) | Proportion of participants achieving procedural success, defined as successful revascularization of the target lesion with residual stenosis below the pre-specified threshold and no major periprocedural complication. |
| Procedure time | During the index procedure (Day 0) | Total time of the index endovascular procedure, in minutes. |
| Contrast use | During the index procedure (Day 0) | Total volume of iodinated contrast used during the index procedure, in milliliters. |
| Change in quality of life | Baseline, 1, 3, 6 and 12 months | Change from baseline in health-related quality of life, measured with one generic and two disease-specific instruments: 1. EQ-5D-5L (EuroQol 5-Dimension 5-Level): the descriptive system yields an index value ranging from less than 0 to 1 (1 = full health; higher scores = better quality of life), accompanied by the EQ Visual Analogue Scale scored 0 to 100 (higher = better health). 2. VascuQoL-6 (Vascular Quality of Life Questionnaire, 6-item): total score ranges from 6 to 24 (higher scores = better quality of life). 3. WIQ (Walking Impairment Questionnaire): score ranges from 0 to 100 (higher scores = better, i.e., less walking impairment). |
| Change in ankle-brachial index | Baseline, 1, 3, 6, 9 and 12 months | Change from baseline in ankle-brachial index (ABI) |
| Change in toe-brachial index | Baseline, 1, 3, 6, 9 and 12 months | Change from baseline in toe-brachial index (TBI) |
| Change in transcutaneous oxygen pressure | Baseline, 1, 3, 6, 9 and 12 months | Change from baseline in transcutaneous oxygen pressure (TcPO2) |
Countries
Taiwan
Contacts
CONTACTDonna SH Lin, MD
PRINCIPAL_INVESTIGATORDonna SH Lin, MD
Shin Kong Wu Ho-Su Memorial Hospital
Outcome results
None listed