Efficacy and Tolerance of RHEOpheresis in the Treatment of Peripheral Artery Disease in Hemodialysis Patients (RHEO-PAD)

Efficacy and Tolerance of RHEOpheresis in the Treatment of Peripheral Artery Disease in Hemodialysis Patients: a Prospective Randomized Single-blind Trial

Peripheral arterial disease (PAD) with limb-threatening ischemia (PAD-LTI) involves both macrocirculation and microcirculation. Macrocirculatory abnormalities are accessible to revascularization techniques (endovascular or surgical) contrary to microcirculatory abnormalities. Conservative treatments have limited efficacy in patients with end-stage renal disease (ESRD). There is no alternative treatment for patients with PAD-LTI in hemodialysis.

Rheopheresis is an apheresis technique specifically designed for the treatment of microcirculatory disorders in which anomalies of rheology are at the center of physiopathology. This double cascade plasma filtration technique reduces plasma viscosity and eliminates inflammation mediators which play an essential role in PAD. This technique has already shown its effectiveness in a randomized trial in dry Age-related macular degeneration (AMD), another pathology of microcirculation. The effectiveness of rheopheresis in PAD-LTI has only been reported in a small number of cases.

This Hypothesis is that the treatment of microcirculation by rheopheresis would improve wound healing of the ischemic lesion and/or reduce major amputation and thus the prognosis of the affected limb of the patient with PAD-LTI in hemodialysis. This objective is to demonstrate the efficacy of rheopheresis, (twelve sessions), to avoid major amputation and reaches complete wound healing of ischemic lesion in the dialysis patient population with PAD-LTI. This study is prospective, Controlled, Parallel, Randomized, Single blind and Multicentric in France (12 French centers).

Study Overview

• Status: Recruiting
• Conditions: Hemodialysis
• Intervention / Treatment: Procedure: Rheopheresis procedure; Biological: Blood Sample; Procedure: Shamapheresis procedure

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas ROBERT, PH; Phone Number: +33 491384095; Email: thomas.robert@ap-hm.fr
• Study Contact Backup: Name: Jean-Olivier ARNAUD, Director; Phone Number: +33 491382747; Email: drci@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Contact: Thomas ROBERT, PH; Phone Number: +33 491384095; Email: thomas.robert@ap-hm.fr
    • Contact: Jean-Olivier ARNAUD, Director; Phone Number: +33 491382747; Email: drci@ap-hm.fr
    • Principal Investigator: Thomas ROBERT, PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or more
• End stage renal disease (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: arterial pressure assessment at the ankle <70 millimeter of mercury (mmHg), or toe pressure 30 mmHg, or transcutaneous oximetry measurements < 40 mmHg
• Interventional or surgical revascularization either not technically possible or no necessary. Or if revascularization has already been performed and the diagnosis of chronic critical ischemia is maintained.
• Female of childbearing potential, will have to use highly effective methods of contraception from study start to the end.
• Medical insurance
• Signed informed consent

Exclusion Criteria:

• Need for revascularization either endovascular (angioplasty) or surgery (bypass) of the ischemic lesion area
• Pregnancy or breastfeeding and all the other categories of people with special protection according to the French Code de la Santé Publique (CSP): patients under legal supervision, patients hospitalized without contentment, patients admitted in social or sanitary structures for care and not research, and patients in emergency situations
• Uncontrolled infection (persistence of fever despite appropriate antibiotic therapy)
• Life expectancy greater than 1 year
• Severe cognitive or psychiatric disorders
• History of allergic reaction to dialysis membrane
• Patients unable to give an informed consent or unwilling to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the rheopheresis group	Procedure: Rheopheresis procedure; 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: Blood Sample; Biological analysis
Placebo Comparator: the shamapheresis group	Biological: Blood Sample; Biological analysis; Procedure: Shamapheresis procedure; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of complete wound healing of the ischemic lesions	Complete wound healing will be assessed clinically by complete epithelialization of the ischemic lesion	8 months
Percentage of absence of major amputation.	Major amputation will be defined as above-the-knee amputation (AKAs) and below-the-knee amputation above the ankle (BKAs)	8 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Estimated): June 12, 2024
• Study Completion (Estimated): June 12, 2024

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: June 4, 2019
• First Posted (Actual): June 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: 2018-68; 2019-A01513-54 (Other Identifier: ID RCB); RCAPHM18_0384 (Other Identifier: AP-HM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No