Rheopheresis Mechanism in Hemodialysis Patients With PAD

NCT ID: NCT05373524

Last Updated: 2022-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-30

Study Completion Date

2024-05-31

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.

Conditions

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Hemodialysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Rheopheresis procedure/Shamapheresis procedure
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
The efficacy will be assessed by a vascular surgeon blinded to the study group during consultation

Study Groups

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the rheopheresis group

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.

Group Type ACTIVE_COMPARATOR

Biological analysis

Intervention Type BIOLOGICAL

Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis

the shamapheresis group

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.

Group Type PLACEBO_COMPARATOR

Biological analysis

Intervention Type BIOLOGICAL

Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis

Interventions

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Biological analysis

Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis

Intervention Type BIOLOGICAL

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Grenoble Alps

OTHER

Sponsor Role collaborator

University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Grenoble University Hospital

Grenoble, , France

Site Status

Countries

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France

Central Contacts

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HAMZA MD NACIRI BENNANI

Role: CONTACT

33476765460

Facility Contacts

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Hamza Naciri Bennani, MD

Role: primary

+33476765460

References

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Roustit M, Cracowski JL. Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci. 2013 Jul;34(7):373-84. doi: 10.1016/j.tips.2013.05.007. Epub 2013 Jun 21.

Reference Type BACKGROUND
PMID: 23791036 (View on PubMed)

Meyer A, Fiessler C, Stavroulakis K, Torsello G, Bisdas T, Lang W; CRITISCH collaborators. Outcomes of dialysis patients with critical limb ischemia after revascularization compared with patients with normal renal function. J Vasc Surg. 2018 Sep;68(3):822-829.e1. doi: 10.1016/j.jvs.2017.12.048. Epub 2018 Mar 26.

Reference Type RESULT
PMID: 29598891 (View on PubMed)

Lowry D, Saeed M, Narendran P, Tiwari A. The Difference Between the Healing and the Nonhealing Diabetic Foot Ulcer: A Review of the Role of the Microcirculation. J Diabetes Sci Technol. 2017 Sep;11(5):914-923. doi: 10.1177/1932296816658054. Epub 2016 Jul 10.

Reference Type RESULT
PMID: 27390224 (View on PubMed)

Weiss N. A critical review on the use of lipid apheresis and rheopheresis for treatment of peripheral arterial disease and the diabetic foot syndrome. Semin Dial. 2012 Mar-Apr;25(2):220-7. doi: 10.1111/j.1525-139X.2011.01036.x. Epub 2011 Dec 16.

Reference Type RESULT
PMID: 22175277 (View on PubMed)

Ferrannini M, Vischini G, Staffolani E, Scaccia F, Miani N, Parravano MC, Louis MM, Splendiani G, Di Daniele N. Rheopheresis in vascular diseases. Int J Artif Organs. 2007 Oct;30(10):923-9. doi: 10.1177/039139880703001010.

Reference Type RESULT
PMID: 17992654 (View on PubMed)

Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Kustner E. Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial. Ther Apher Dial. 2003 Aug;7(4):444-55. doi: 10.1046/j.1526-0968.2003.00082.x.

Reference Type RESULT
PMID: 12887730 (View on PubMed)

Kirschkamp T, Schmid-Schonbein H, Weinberger A, Smeets R. Effects of fibrinogen and alpha2-macroglobulin and their apheretic elimination on general blood rheology and rheological characteristics of red blood cell aggregates. Ther Apher Dial. 2008 Oct;12(5):360-7. doi: 10.1111/j.1744-9987.2008.00610.x.

Reference Type RESULT
PMID: 18937718 (View on PubMed)

Briers JD. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001 Nov;22(4):R35-66. doi: 10.1088/0967-3334/22/4/201.

Reference Type RESULT
PMID: 11761081 (View on PubMed)

Roustit M, Millet C, Blaise S, Dufournet B, Cracowski JL. Excellent reproducibility of laser speckle contrast imaging to assess skin microvascular reactivity. Microvasc Res. 2010 Dec;80(3):505-11. doi: 10.1016/j.mvr.2010.05.012. Epub 2010 Jun 9.

Reference Type RESULT
PMID: 20542492 (View on PubMed)

Choi B, Ramirez-San-Juan JC, Lotfi J, Stuart Nelson J. Linear response range characterization and in vivo application of laser speckle imaging of blood flow dynamics. J Biomed Opt. 2006 Jul-Aug;11(4):041129. doi: 10.1117/1.2341196.

Reference Type RESULT
PMID: 16965157 (View on PubMed)

Stewart CJ, Frank R, Forrester KR, Tulip J, Lindsay R, Bray RC. A comparison of two laser-based methods for determination of burn scar perfusion: laser Doppler versus laser speckle imaging. Burns. 2005 Sep;31(6):744-52. doi: 10.1016/j.burns.2005.04.004.

Reference Type RESULT
PMID: 16129229 (View on PubMed)

Other Identifiers

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38RC20.461

Identifier Type: -

Identifier Source: org_study_id

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