Combined Apheresis for ABO-incompatible Transplantation - a Pilot Study

NCT02120482 | Terminated DMC

• 1 other identifier: EK2123/2013
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Recipient desensitization is a prerequisite for successful ABO-incompatible kidney transplantation (ABOi-KTX). Published desensitization protocols commonly include the use of plasmapheresis or selective (i.e. antigen-specific) immunoadsorption (IA), together with distinct immunomodulatory measures (e.g. CD20 antibody rituximab). Selective IA represents an efficient but cost-intensive therapy. An alternative could be the use of semi-selective (non-antigen-specific) IA. Even though highly efficient in depleting ABO-specific IgG, semi-selective IA may only marginally affect levels of ABO-specific IgM, which might - due to the strong complement activating potential of this Ig class - exhibit a potential risk for (hyper)acute antibody-mediated rejection (Wahrmann et al. 2012, Nephrol Dial Transplant). In a randomized crossover trial (Eskandary et al. 2014, Nephrol Dial Transplant; www.clinicaltrials.gov, NCT01698736) we have recently shown that the combination of semi-selective IA together with membrane filtration, a technique primarily used in the field of LDL apheresis, can yield excellent elimination of both IgM and IgG reactivities, as well as essential macromolecules such as the classical complement key component C1q. In this two-center phase 2 pilot study (N=10) we plan to evaluate the safety and efficacy of this alternative desensitization strategy in ABOi-KTX.

Conditions

Decreased Immunologic Activity; Antibody-mediated Rejection

Keywords

ABO isoagglutinins; ABO incompatible transplantation; immunoadsorption; membrane filtration; plasmapheresis

Outcome Measures

Primary Outcomes (1)

• The incidence of antibody-mediated rejection (AMR) within three months after transplantation

  Antibody-mediated rejection according to Banff 2013 criteria

  First three months after transplantation

Secondary Outcomes (20)

• Successful desensitization for ABOi transplantation

  Day of transplantation

• Kidney function

  First six months after transplantation

• Rate of cellular rejection

  First six months after transplantation

• Graft survival

  First six months after transplantation

• Patient survival

  First six months after transplantation

Study Arms (1)

Combined apheresis

EXPERIMENTAL

Patients will be treated by semiselective immunoadsorption combined with membrane filtration

Device: Combined apheresis

Interventions

Combined apheresis DEVICE

Semiselective immunoadsorption combined with membrane filtration

Also known as: MONET, GLOBAFFIN

Combined apheresis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility for living donor ABO-incompatible kidney transplantation according to center standard
• Age \>18 years
• Signed written informed consent
• Negative cytotoxic and flow-cytometric crossmatch

You may not qualify if:

• Age\<18 years
• No signed written informed consent
• Blood group AB (no isoagglutinins)
• Pregnant and breastfeeding women
• HLA-sensitized patients (i.e. patients with preformed antibodies against donor HLA antigens)
• Positive cytotoxic and flow-cytometric crossmatch
• Severe blood coagulation disorder precluding the use of membrane filtration or immunoadsorption
• Initial serum fibrinogen \<200mg/dL
• IgA deficiency
• Any severe disease (e.g. severe infection) precluding ABOi-KTX
• Heparin intolerance
• Polysulfone intolerance
• Participation in any other intervention trial

Sponsors & Collaborators

• Medical University of Vienna: lead
• Elisabethinen Hospital: collaborator

Study Sites (1)

Division of Medicine III, Dpt. of Nephrology and Dialysis, Medical University Vienna

Vienna, 1090, Austria

Location

Related Publications (2)

• Eskandary F, Wahrmann M, Biesenbach P, Sandurkov C, Konig F, Schwaiger E, Perkmann T, Kunig S, Derfler K, Zlabinger GJ, Bohmig GA. ABO antibody and complement depletion by immunoadsorption combined with membrane filtration--a randomized, controlled, cross-over trial. Nephrol Dial Transplant. 2014 Mar;29(3):706-14. doi: 10.1093/ndt/gft502. Epub 2013 Dec 29.

  PMID: 24378525 BACKGROUND

• Wahrmann M, Schiemann M, Marinova L, Kormoczi GF, Derfler K, Fehr T, Stussi G, Bohmig GA. Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption. Nephrol Dial Transplant. 2012 May;27(5):2122-9. doi: 10.1093/ndt/gfr610. Epub 2011 Nov 15.

  PMID: 22086972 BACKGROUND

Related Links

• Website of the VIETAC Lab

Study Officials

• Georg A Böhmig, MD

  Medical University Vienna, Division of Medicine III, Dpt. of Nephrology and Dialysis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: April 22, 2014
• Study Start: October 1, 2014
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: August 24, 2022

Record last verified: 2022-08

Locations

AU (1)