Rheopheresis Mechanism in Hemodialysis Patients With PAD

Study Overview
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Brief Summary
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Peripheral arterial disease (PAD) is common in chronic hemodialysis patients (HDC) with a prevalence of 30% according to the DOPPS study. The combination of PAD and chronic kidney disease (CKD) stage 5 is a risk factor for major amputation (24.5%) with a mortality rate of 55% at 2 years. Ischemia occurring during PAD is the result of impaired microcirculation, with insufficient blood flow to maintain tissue perfusion and viability. It is responsible for painful skin wounds whose healing is poor, with a significant risk of infection. In patients with chronic renal failure, it is linked to both: local phenomena (atherosclerosis, calcification) changes in blood viscosity (elevated hematocrit and inflammatory proteins, especially fibrinogen) a neovascularization defect (uremic toxins, in particular indoxyl sulphate). If revascularization is not possible, amputation remains the only possible treatment to relieve pain and limit the risk of infection. Rheopheresis is an apheresis technique that allows the depletion of high molecular weight serum proteins. This would reduce blood viscosity and red blood cell (RBC) aggregation, thereby improving microvascular perfusion, with the aim of reducing pain, improving healing and limiting the risk of amputation. Several studies have investigated the efficacy of rheopheresis in PAD in HDC, but the level of evidence remains low.

Detailed Description
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The main objective of our study is to evaluate the impact of rheopheresis on blood (main objective) and plasma viscosity, skin microcirculation and blood coagulation (Fibrinography, Thrombin Generation). No study has evaluated the direct effect of rheopheresis on these different parameters. However, a better understanding of these mechanisms would make it possible both to optimize the effectiveness of the technique, to limit its potential side effects and the cost of treatment.

Official Title
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Rheopheresis Mechanism of Action and Impacts on the Evolution of Peripheral Arterial Disease in Hemodialysis Patients

Conditions
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Hemodialysis

Intervention / Treatment
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* Biological: Biological analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or more and included in the RHEOPAD protocol (2019-A01513-54) ESRD treated by hemodialysis or hemodiafiltration PAD-LTI with tissue loss and/or wounds (ulcers or gangrene) with at least one of the following criterion, subject to the feasibility of the measures: arterial pressure assessment at the ankle <70 mmHg, or toe pressure 30 mm Hg, or transcutaneous oximetry measurements < 40 mm Hg Interventional or surgical revascularization either not technically possible or no necessary Medical insurance Signed informed consent Exclusion Criteria: - Uncontrolled infection despite well-conducted antibiotic therapy Life expectancy < 1 year Severe cognitive or psychiatric disorders Pregnant woman, parturient, nursing mother Patients unable to give an informed consent or unwilling to participate in 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Rheopheresis procedure/Shamapheresis procedure
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: the rheopheresis group<br>Rheopheresis is performed using an automated monitor in a double-filtration cascade. Plasma purify from of high molecular weight proteins through a secondary filter is then returned to the patient. This technique is performed in tandem with a hemodialysis monitor. | Biological: Biological analysis<br>* Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis<br>|
| Placebo Comparator: the shamapheresis group<br>Shamapheresis is performed with the same automated monitor (Plasauto, HemaT company). Extracted plasma is not treated through the secondary filter (Rheofilter) and return to the patient. This technique is performed in tandem with a hemodialysis monitor. | Biological: Biological analysis<br>* Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood viscosity measured by rotational rheometer | To assess the effect of rheopheresis on blood viscosity of chronic hemodialysis patients with PAD | Immediately before 1ST and immediately after 12th procedure , outcome measurement will be reported at the end of the study (approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood viscosity measured by rotational rheometer | Evaluate the effect of rheopheresis on blood viscosity measured by rotational rheometer before the 12th treatment session | up to 24 weeks |