Polytetrafluoroethylen (PTFE) Vascular Prostheses With Heparin Bonded Luminal Surfaces vs Crude ePTFE

Study Overview
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Brief Summary
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Open repair could be recommended in a first line of treatment to revascularize critical limb ischemia patients or performed in a second line of treatment in case of failure of endovascular repair. A good quality vein is one of the main factors that influence the clinical success of open revascularization for below-knee popliteal. In the absence of an suitable autologous vein, prosthesis such as polytetrafluoroethylen (PTFE) graft could be an option but demonstrated worse clinical and morphological results compared to autologous greater saphenous vein. Consequently, there is still a room for improvement in CLI patients in the absence of an suitable autologous vein in whom endovascular repair failed. Recently, PTFE with heparin-bound to the luminal surface (Hb-PTFE) significantly reduced the overall risk of primary graft failure by 37%, in particular, risk reduction was 50% in femoropopliteal bypass cases in cases with critical ischemia (58% Primary patency for crude ePTFE versus 80% primary patency for PROPATEN at 1 year follow-up) (Lindholt, et. al. 2011). Additionally, a weighted average from the literature suggests a 76% primary patency for below knee bypasses performed with PROPATEN at one year follow-up, whereas a published meta-analysis suggests a 59% primary patency for below knee crude ePTFE at one year follow-up. At two year follow-up using the same approach, the average primary patency for PROPATEN was 67% versus 43% for standard ePTFE. The aim of this study is to assess PTFE with heparin-bound to the luminal surface as an alternative to crude PTFE in absence of good venous conduit in patients with CLI.

Detailed Description
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Patient inclusion in this study will be proposed 60 to 1-days period preceding the surgical procedure. The patient will be randomized in the crude PTFE or in the Propaten groups. Regarding the intervention, the technique used during the therapeutic procedure shall be left to the operator's discretion, except the type of the graft. Demographic, intraoperative and postoperative data will be collected prospectively. Patient will be assessed and followed up according a current care. The cost difference between both groups will be identified.

Official Title
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Polytetrafluoroethylen (PTFE) Vascular Prostheses With Heparin Bonded Luminal Surfaces vs Crude ePTFE in the Treatment of Critical Limb Ischemia Lesions in the Absence of a Suitable Autologous Vein

Conditions
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Ischemia Lesions

Intervention / Treatment
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* Procedure: revascularization
* Device: Propaten®
* Device: Crude PTFE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥18 years Patient presented critical limb ischemia (Rutherford classification: 4-6) Indication of below the knee bypass with an artificial graft Absence of an suitable autologous vein Patient is affiliated to the Social Security or equivalent system Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site Exclusion Criteria: No atheromatous disease Female of child bearing potential Patient has a history of coagulopathy or will refuse blood transfusions Patient is receiving or scheduled to receive anticancer therapy for malignancy within 1 year prior to or after the procedure Severe concomitant disease with life expectation < one year Known allergy to heparin Indication for ipsilateral major amputation Patient is not able to give informed consent Patient is currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints Note: Trials requiring extended follow-up for products that were investigational, but have become commercially suitable since then, are not considered investigational trials In the Investigator's opinion patient has (a) co-morbid condition(s) that could limit the patient's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revascularization by (Propaten)®<br>Revascularization by PTFE with heparin bonded luminal surface (Propaten)® | Procedure: revascularization<br>* open revascularization for below-knee popliteal in the absence of an suitable autologous vein with PTFE.<br>Device: Propaten®<br>* Propaten®<br>|
| Active Comparator: Revascularization by Crude PTFE<br> | Procedure: revascularization<br>* open revascularization for below-knee popliteal in the absence of an suitable autologous vein with PTFE.<br>Device: Crude PTFE<br>* Crude PTFE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary patency at 1 year: | It was defined as a patent graft without any intervention to open up or prevent a graft occlusion. Demonstrably patent graft should be by a duplex ultrasound color-flow scan. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success defined as a patent bypass without stenosis of the proximal and the distal anastomoses. | Stenosis was defined as >30% diameter stenosis noted on intraoperative arteriography. | 2 years | 
| Perioperative complications | defined as any general complications or local complications that caused or prolonged hospitalization and/or re-intervention, lymphorrhea of more than 3-days and post-operative paresthesia that required drugs. The general complications included death from any cause, MACE. Local complications included MALE, hematoma, active bleeding, local infection, thrombosis, delayed wound healing and false aneurysm | 2 years | 
| Primary sustained clinical improvement | defined as a wound healing and rest pain resolution for patients in CLI, without the need for repeated graft it self or anastomoses in surviving patients. | 1, 12 and 24 months post procedure | 
| Secondary sustained clinical improvement | defined as primary sustained clinical improvement including the need for repeated graft it self or anastomoses. | 1, 12 and 24 months post procedure | 
| Primary patency | defined as a patent graft without any intervention to open up or prevent a graft occlusion. Demonstrably patent graft should be by a duplex ultrasound color-flow scan. | 1 and 24 months post procedure | 
| Major adverse cardiovascular events | defined as MACEs including all cardiac deaths, Q wave infarction, stroke | 1, 12 and 24 months post procedure | 
| MALE (Major Adverse Limb Event)-free survival rates in subjects with CLI randomized to Propaten vs. crude ePTFE. | MALE is defined as above-ankle amputation of the index limb or major reintervention (new bypass graft, jump/interposition graft revision, or thrombectomy/ thrombolysis). | 1, 6, 12 and 24 months | 
| Limb salvage defined as freedom from above-ankle amputation of the index limb |  | 1, 12 and 24 months post procedure | 
| Secondary patency | secondary patency in which graft patency is lost (occlusion) and restored by thrombectomy, thrombolysis, or transluminal angioplasty, and/or any problems with the graft itself or one of its anastomoses require revision or reconstruction. Demonstrably patent graft should be by a duplex ultrasound color-flow scan. | 1, 12 and 24 months post procedure | 
| Assisted patency | : Assisted patency at 1, 12 and 24 months post procedure, in which patency was never lost but maintained by prophylactic intervention. Demonstrably patent graft should be by a duplex ultrasound color-flow scan. | 1, 12 and 24 months post procedure | 
| Death | Death (all cause) | 1, 12 and 24 months post procedure | 
| Ankle brachial index | Post-operative assessment (clinical, morphological, hemodynamic criteria) | 1, 6, 12 and 24 months post procedure | 
| Quality of life at inclusion, . | assessed according the EQ-5D-3L questionnaire | 1, 3, 6, 9, 12, 15, 18 and 24 months | 
| Cost utility analysis (CUA) | In CUA, the outcomes of an intervention are evaluated in terms of Quality-Adjusted Life-Years (QALYs). QALYs are a numerical index that encompasses both the length of life and the health-related quality-of-life. | 2 years | 
| cost-effectiveness analysis (CEA) | The Measure of outcome for CEA will be the number of Life Years Gained (LYG) at 2 years | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vascular prostheses, heparin, ischemia lesions, vascular, critical limb ischemia lesions