Drug-Eluting Balloon Angioplasty Versus Bypass Surgery as First-Line Strategies in Infrageniculate Arterial Disease for Critical Limb Ischemia in Type 2 Diabetic Pacients: a Randomised Controlled Clinical Trial

Study Overview
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Brief Summary
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The aim of this study is to evaluate the outcomes of drug-eluting balloon angioplasty and vein bypass surgery in diabetic patients with critical limb ischemia due to infrapopliteal arterial disease.

Detailed Description
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Objective: To consider the clinical outcomes of drug-coated ballon angioplasty and vein bypass surgery in terms of amputation-free survival, overall survival, relief of symptoms, quality of life and to determine if limb revascularization contributes to diabetic peripheral neuropathy (DPN). All patients with type 2 diabetes mellitus and severe limb ischemia reffered to multidisciplinary diabetic foot team or endocrinology or vascular units can be considered. To be eligible for randomization, peripheral arterial occlusive disease must be located infra-popliteally; patients must have adequate inflow and outflow to support infrapopliteal interventions; have a good superficial vein for bypass surgery. If the patient is suitable for both treatment arms, they will be invited to enter the trial. If patient is suitable for both revascularization techniques randomization will be performed after diagnostic angiogram submission Patient will be randomised to one of the following groups: A. Vein bypass surgery first strategy B. Endovascular treatment first (drug coated balloon angioplasty) strategy Outcomes will be recorded at 1, 3, 6, 9, 12, 18, 24 month after revascularisation procedure. Information collected will include further interventions (vascular, non-vascular), hospitalisations (for whatever reason), other health problems, clinical and haemodinamic status of limbs, funcional status, quality of life, neuropathy.

Official Title
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Drug-Eluting Balloon Angioplasty Versus Bypass Surgery as First-Line Strategies in Infrageniculate Arterial Disease for Critical Limb Ischemia in Type 2 Diabetic Pacients: a Randomised Controlled Clinical Trial

Conditions
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Critical Limb Ischemia

Intervention / Treatment
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* Procedure: Vein bypass surgery first strategy
* Procedure: Endovascular treatment first (drug coated balloon angioplasty) strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with type 2 diabetes mellitus Severe limb ischemia (Rutherford class >=4) due to infrapopliteal, +/- popliteal disease [ a.tibialis anterior, tr.tibioperonealis, a.peronea, a.tibialis posterior, a.dorsalis pedis stenosis or occlusion (50%-100%; >40mm in length); leasion may involve a.poplitea P1-P3 segment; have adequate inflow and outflow to support infrapopliteal intervention (diagnostic imaging); suitable for both vein bypass and best endovascular treatment following; angiography diagnostic imaging and ultrasound examination of vein conduit.] Exclusion Criteria: Requires primary limb amputation Acute limb ischemia Anticipated life expectancy of <2 years Unsuitable for either revascularisation strategy Severe concomitant disease (acute coronary ischemic event, brain ischemic event, cognitive disorder, active oncology process)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The treatment will consist of two treatment modalities: 1) Vein bypass surgery first strategy; 2) Endovascular treatment first (drug coated balloon angioplasty) strategy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vein bypass surgery first strategy<br> | Procedure: Vein bypass surgery first strategy<br>* Vein bypass will be performed with standart anaesthetic and surgical techniques using reversed great saphenous vein conduit. Location of proximal and distal anastomosis will be recorded. Post surgery completion angiography imaging will be performed.<br>|
| Active Comparator: Endovascular treatment first (drug coated balloon angioplasty) strategy<br> | Procedure: Endovascular treatment first (drug coated balloon angioplasty) strategy<br>* Endovascular treatment using drug-coated balloons will be performed under local anaesthetic via common femoral artery. Final angiography imaging will be demonstrated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary, primary-assisted and secondary patency | Clinical and ultrasound assesment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ischemic symptoms | Fontaine classification: I asymptomatic; IIa mild claudication; IIb moderate-to-severe claudication; III rest pain; IV ulceration or gangrene. Rutherford classification: 0 asymptomatic; 1 mild claudication; 2 moderate claudication; 3 severe claudication; 4 rest pain; 5 minor tissue loss; 6 severe tissue loss or gangrene. | 24 months | 
| Ankle-brachial index (ABI) | Ratio of the blood pressure at the ankle to the blood pressure in the upper arm. Norm 1.0-1.4 | 24 months | 
| Toe-brachial index (TBI) | Ratio of the blood pressure of the great toe to the blood pressure in the upper arm. Norm 1.0-1.4 | 24 months | 
| Transcutaneous oxygen tension (TcPO2) | A noninvasive test that directly measures the oxygen level of tissue beneath the skin. A TcPO2 greater than 55 mmHg is considered normal regardless of the site of measurement, whereas a value of 40 mmHg is the critical value below which wound healing is impaired and ischemia develops. | 24 months | 
| Healing of tissue loss (ulcers, gangrene) | Clinical examination and photo documentation. | 24 months | 
| Re- and cross-over intervention rates |  | 24 months | 
| Major and minor amputation rates |  | 24 months | 
| In-hospital morbidity/mortality and overall survival |  | 24 months | 
| Relief of pain: Visual analog scale (VAS) | The Visual Analog Scale (VAS) is a 10 cm line with anchor statements on the left (no pain) and on the right (extreme pain). | 24 months | 
| Quality of life: EQ-5D-5L questionaire | Descriptive system for health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain & discomfort, Anxiety & depression), each of which has five severity levels that are described by statements appropriate to that dimension. | 24 months | 
| Diabetic neuropathy dinamics: clinical examination of foot sensation | Full hypoesthesia; Partial hypoesthesia; No changes; + Assymetry. | 24 months | 
| Diabetic neuropathy dinamics: neurometer | Perception threshold measurement. Neurometer® determines three sub-types of nerve fiber by producing transcutaneous electrical stimuli at frequencies of 2000, 250 and 5 Hz. | 24 months | 
| Diabetic neuropathy dinamics: electroneuromiography | Diagnostic procedure that evaluates the health condition of muscles and the nerve cells that control them. A nerve conduction velocity between 50 and 60 meters per second is generally considered in the normal range. | 24 months |