Treatment of Chronic Active Antibody Mediated Rejection After Kidney Transplantation by Double-Filtration PlasmaPheresis or Plasma Exchange

NCT03436134 | Unknown

• 1 other identifier: 38RC17.246
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

In France around 90,000 cases of end-stage chronic kidney disease patients treated either by dialysis (60%) or renal transplantation (just over 40%). In terms of patient survival and quality of life and also economic reasons, the goal in France is to increase renal transplantation instead of patients on dialysis. After renal transplant, two main causes of the graft loss after the first years are death of patient with functioning graft, and chronic AntiBody Mediated Rejection (ABMR). Double Filtration PlasmaPheresis (DFPP) has never been evaluated for this indication. DFPP makes it possible to treat larger volumes of plasma than plasma exchange, and essentially eliminates higher molecular weights molecules including immunoglobulins comprising DSA (donor-specific alloantibody) but also the C1q involved in the lesions of(ABMR). It is postulated that it will be more effective in treating ABMR than usual plasma exchanges. A chronic ABMR is the result of the appearance de novo production of anti-Human Leucocyte Antigen antibodies (HLA) against one or more graft antigens (DSA: donor-specific alloantibody).These DSAs will lead to accelerated arteriosclerosis in the graft vessels, which will result in rapidly progressive renal failure, usually associated with a high rate of proteinuria. Numerous studies have shown that up to 20% of renal transplant patients develop DSA within 5 years of renal transplantation. Today, no treatment has been shown to be effective in the case of chronic ABMR: the basis of treatment is the reduction/elimination of DSA ( by apheresis for example) and the prevention of its re-synthesis B lymphocytes/plasma cells of the patient (with rituximab for example). The investigators of this study propose in the context of the active ABMR demonstrated by renal biopsy to evaluate in combination with rituximab, a new apheresis technique double Plasma filtration (DFPP) instead of plasma Exchange.

Conditions

Kidney Transplantation; Antibody Mediated Rejection

Keywords

Donor-specific antibodies; Double-Filtration PlasmaPheresis (DFPP); Plasma Exchange (PE)

Outcome Measures

Primary Outcomes (1)

• show that renal transplant patients with chronic antibody mediated rejection treated with rituximab and DFPP (instead of plasmapheresis +rituximab) had a greater decrease of DSA at 45 days after the end of treatment.

  Measurement of Delta DSA ( evaluated MFI) between Day 45 post-treatment and D0 treatment for every patient in each group

  DSA at the first session of the treatment Day1 - At Day 45 post-treatment.

Secondary Outcomes (7)

• Evaluate of the coagulation parameters (factors II, V, VII, VIII, IX, X, XI, XII, XIII, Von Willebrand and fibrinogen) before/after each session, for each technique (safety)

  At day1,day4, day8, day 11, day 45, month 6, month12

• Evaluate of the serum albumin before/after in each session for each technique (safety)

  At day1,day4, day8, day 11, day 45,month 3, month 6, month 9, month12

• Evaluate the complement components C3,C4,C5,C5-9, mannose- binding lectin (MBL) Ficoline3, Properdin and C1q before and after each session for each technique (efficacy)

  At day1,day4, day8, day 11, day 45, month 6, month12

• Evaluate the immunoglobulin levels(Immunoglobulin G(IgG) , immunoglobulin A: (IgA), immunoglobulin M(IgM)) before and after each session for each technique

  At day1,day4, day8, day 11, day 45, month 6, month12

• Evaluate the DSA before the first and after the last session of apheresis in each technique

  At day1,day 11, day 45, month 6, month12

Study Arms (2)

Plasma Exchange Group

ACTIVE COMPARATOR

Patients receiving Exchange plasma as a treatment of chronic antibody mediated rejection.

Other: Sessions of conventional apheresis

Double filtration PlasmaPheresis Group

EXPERIMENTAL

Patients receiving double filtration plasmapheresis as a treatment of chronic antibody mediated rejection.

Other: Sessions of news apheresis with double filtration

Interventions

Sessions of conventional apheresis OTHER

Patient receiving sessions of Plasma exchange as treatment of chronic antibody mediated rejection. The plasma exchange uses a single filter to remove whole plasma and the volume is replaced with a matched volume of blood products +/- saline.) 8 sessions plasma exchange.Patients will have one session per day, 4 consecutive days and then three days without, then one session per day for 4 consecutive days. That's 11 days of treatment at all. The fourth and eighth sessions will be followed by an infusion of Rituximab 375 mg / m2. At the beginning and at the end of each session, the patients will have a blood test to measure the parameters of the routine care and the analyzes, collection of biological samples planned for the study.

Plasma Exchange Group

Sessions of news apheresis with double filtration OTHER

Patient receiving DFPP as treatment of chronic antibody mediated rejection. 8 sessions A Double filtration plasmapheresis (DFPP) is a variation of plasma exchange. The circuit contains two plasma filters : the first is a standard plasma filter and the second is a high molecular weight filter that primarily removes immunoglobulins. The depleted plasma is returned to the blood circuit and then to the patient.

Double filtration PlasmaPheresis Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplantation for more than 6 months
• The presence of one or more DSAs with MFI greater than 1000
• Renal Graft dysfunction with renal biopsy of humoral rejection or chronic active antibody mediated rejection lesions based on the 2017 banff score ( with/without C4d)
• Written informed consent in patients

You may not qualify if:

• Kidney transplant for less than 6 months.
• MFI\<1000
• Hemoglobin level\<110 g/l
• No vascular access patients
• Pre terminal histological lesions of chronic ABMR
• Pregnant women, parturient or breastfeeding
• Subject under administrative or judicial control

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Grenoble Alpes University Hospital

La Tronche, 38700, France

RECRUITING

Related Publications (5)

• Eskandary F, Bond G, Kozakowski N, Regele H, Marinova L, Wahrmann M, Kikic Z, Haslacher H, Rasoul-Rockenschaub S, Kaltenecker CC, Konig F, Hidalgo LG, Oberbauer R, Halloran PF, Bohmig GA. Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection-Results of a Cross-Sectional Screening Study. Transplantation. 2017 Mar;101(3):631-641. doi: 10.1097/TP.0000000000001195.

  PMID: 27120452 RESULT

• Eskandary F, Wahrmann M, Muhlbacher J, Bohmig GA. Complement inhibition as potential new therapy for antibody-mediated rejection. Transpl Int. 2016 Apr;29(4):392-402. doi: 10.1111/tri.12706. Epub 2015 Nov 10.

  PMID: 26474721 RESULT

• Gatault P, Kamar N, Buchler M, Colosio C, Bertrand D, Durrbach A, Albano L, Rivalan J, Le Meur Y, Essig M, Bouvier N, Legendre C, Moulin B, Heng AE, Weestel PF, Sayegh J, Charpentier B, Rostaing L, Thervet E, Lebranchu Y. Reduction of Extended-Release Tacrolimus Dose in Low-Immunological-Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor-Specific Antibodies: A Randomized Study. Am J Transplant. 2017 May;17(5):1370-1379. doi: 10.1111/ajt.14109. Epub 2017 Jan 3.

  PMID: 27862923 RESULT

• Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D, Nankivell BJ, Colvin RB, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell L, Drachenberg C, Dragun D, de Kort H, Gibson IW, Kraus ES, Lefaucheur C, Legendre C, Liapis H, Muthukumar T, Nickeleit V, Orandi B, Park W, Rabant M, Randhawa P, Reed EF, Roufosse C, Seshan SV, Sis B, Singh HK, Schinstock C, Tambur A, Zeevi A, Mengel M. The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology. Am J Transplant. 2017 Jan;17(1):28-41. doi: 10.1111/ajt.14107.

  PMID: 27862883 RESULT

• Hanafusa N, Kondo Y, Suzuki M, Nakao A, Noiri E, Fujita T. Double filtration plasmapheresis can decrease factor XIII Activity. Ther Apher Dial. 2007 Jun;11(3):165-70. doi: 10.1111/j.1744-9987.2007.00433.x.

  PMID: 17497996 RESULT

Study Officials

• Lionel Rostaing, PH.MD

  Nephrology Dialysis Transplantation/ CHU GRENOBLE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amjad UNEISI, ARC prom

CONTACT

(0)4 76 76 81 08; AUneisi@chu-grenoble.fr

Farida Imerzoukene, ARC

CONTACT

(0)4 76 76 70 22; fimerzoukene@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 19, 2018
• Study Start: July 1, 2018
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2021
• Last Updated: March 27, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)