Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates

NCT ID: NCT03477656

Last Updated: 2024-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-02
• Study Completion Date: 2023-10-03

Brief Summary

Kidney transplantation is the treatment of choice for end-stage renal disease. ABO incompatible (ABOi) living donor kidney transplantation is one of the best ways to expand the donors' pool. However, breaking the ABO barrier is possible only with a preconditioning regimen that includes 1) an immunosuppressive strategy using a B-cell depleting agent (rituximab), an induction therapy with polyclonal antibodies, and a maintenance triple immunosuppressive therapy based on calcineurin inhibitors, and 2) a desensitization protocol aiming to decrease the titer of isoagglutinins. For this purpose, several techniques of apheresis are available. To date, two main techniques used in clinical setting are the Double-Filtration PlasmaPheresis (DFPP) and the Antigen-Specific Immunoadsorption (SIA). DFPP permits the depletion of the selective plasma fraction containing Immunoglobulins, while limiting the need for plasma substitution. SIA enables to remove ABO antibodies without a major loss in essential plasma components. To date, no randomized study comparing DFPP and SIA exist. SIA is less often used because of its high cost. However, in order to reduce the number of SIA sessions and consequently its cost, large plasma volume sessions of SIA are performed. ABOi is dramatically more expensive than ABO compatible kidney transplantation. A large part of the difference in the cost is related to the apheresis technique.

Herein, the investigator proposes to describe the efficacy, the safety, and the cost of DFPP and SIA to desensitize ABO incompatible kidney transplant candidates.

Detailed Description

All recipients will receive an induction therapy with rituximab and polyclonal antibodies, as well as a maintenance therapy by tacrolimus, mycophenolic acid (switched for mTOR (Mechanistic target of rapamycin) inhibitors 1 month after the transplantation to avoid viral infections) and steroids.

The desensitization protocol will be based on the initial titer of isoagglutinin. All patients with an isoagglutinin titer between 1/8 and 1/128 will be included in this monocentric, open label study, and randomized between the DFPP arm (1 to 4 sessions according to the initial titer) and large-plasma SIA (1 to 2 sessions according to the titer). The effectiveness will be evaluated on the ability to obtain the targeted titer before transplantation (1/4) with less than 5 DFPP, or 2 large-plasma volume SIA.

All recipients will be followed for 6 months, and examined for surgical complications, rejection rate, and kidney function. All complications related to desensitization protocol will be reported. Moreover, all cost associated with these two apheresis techniques will be evaluated.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Large volume specific immunoadsorption

1 to 2 sessions of large volume specific immunoadsorption according to the initial isoagglutinin titer.

Group Type: EXPERIMENTAL

Large volume specific immunoadsorption

Intervention Type: PROCEDURE

1 to 2 sessions of large volume specific immunoadsorption using GLYCOSORB®-ABO column

Double Filtration Plasmapheresis

1 to 5 sessions of double filtration plasmapheresis according to the initial isoagglutinin titer.

Group Type: EXPERIMENTAL

Double Filtration Plasmapheresis

Intervention Type: PROCEDURE

1 to 5 sessions of double filtration plasmapheresis

Interventions

Large volume specific immunoadsorption

1 to 2 sessions of large volume specific immunoadsorption using GLYCOSORB®-ABO column

Intervention Type: PROCEDURE

Double Filtration Plasmapheresis

1 to 5 sessions of double filtration plasmapheresis

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patient eligible for living donor ABO incompatible kidney transplantation
• Presenting an IsoAgglutinin immunoglobulin G titer (anti-A-B) between 1/8 and 1/128, before desensitization
• Patient older than 18 years
• Women of childbearing age must have a pregnancy test before starting the study and undergoing study. They must take an effective and acceptable method of contraception before starting the study and throughout the study period. Sexually active men should use a condom throughout the course of the study
• Patient able to sign an informed consent form
• Patient affiliated with a social security scheme

Exclusion Criteria

• Presence of anti-HLA (Human Leucocyte Antigens) allo-antibodies
• Patient with comorbidities that prevent desensitization protocols
• Women who are pregnant, or who may become pregnant or breastfeeding women
• History of hypersensitivity related to a component of the apheresis membrane
• Subjects under legal protection
• Subjects participating in another interventional research protocol or in an exclusion period from another interventional research protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arnaud DEL BELLO, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Toulouse

Locations

University Hospital Toulouse (Hospital Rangueil)

Toulouse, , France

Countries

France

Other Identifiers

RC31/16/8767

Identifier Type: -

Identifier Source: org_study_id