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

Kidney Transplantation Clinical Trial

— DADI  

Official title:

Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates: Double Filtration PlasmaPheresis (DFPP) vs Large Plasma Volume Specific ImmunoAdsorption

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03477656
• Other study ID #: RC31/16/8767
• Status: Completed
• Phase: N/A
• Start date: May 2, 2018
• Est. completion date: October 3, 2023

Study information

• Verified date: April 2024
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Procedure:
• Large volume specific immunoadsorption
1 to 2 sessions of large volume specific immunoadsorption using GLYCOSORB®-ABO column
• Double Filtration Plasmapheresis
1 to 5 sessions of double filtration plasmapheresis

Locations

Country	Name	City	State
France	University Hospital Toulouse (Hospital Rangueil)	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success rate	% of subjects with the targeted isoagglutinin titer (=1/4) before transplantation with less than 5 DFPP sessions (for the DFPP arm) or 2 large plasma volume specific immunoadsorption sessions (for the specific immunoadsorption arm)	the day of transplantation
Secondary	Differential cost-efficacy ratio of support for patients receiving a live donor kidney transplant Incompatible ABO and benefiting from a desensitization procedure	Direct medical costs ( treatments costs, costs of hospital stays, costs of outpatient cares) will be evaluated from the society point of view.; A cost-efficacy analysis, comparative of medical consequences, measured in terms of number of complications related to the technique and post surgical at 7 months, and the economic consequences will be realized.	7 months
Secondary	Surgical complication rate during the desensitization sessions	% of subjects with surgical complications during the desensitization sessions	From the first desensitization session to the last one, assessed up to 10 days
Secondary	Surgical complication rate during the transplantation surgery	% of subjects with surgical complications during the transplantation surgery	During the transplantation surgery
Secondary	Thrombotic complication rate during the desensitization sessions	% of subjects with thrombotic complications during the desensitization sessions	From the first desensitization session to the last one, assessed up to 10 days
Secondary	Thrombotic complication rate 1 week after transplantation surgery	% of subjects with thrombotic complications until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Rate of bleeding and/or hematoma on vascular access during the desensitization sessions	% of subjects with bleeding and/or hematoma on vascular access during the desensitization sessions	From the first desensitization session to the last one, assessed up to 10 days
Secondary	Rate of hematoma occurrence during the transplantation surgery	% of subjects with hematoma during the transplantation surgery	During the transplantation surgery
Secondary	Rate of occurrences of hemorrhage away from vascular access during the desensitization sessions	% of subjects with hemorrhage away from vascular access during the desensitization sessions	From the first desensitization session to the last one, assessed up to 10 days
Secondary	Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions	% of subjects with allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions	From the first desensitization session to the last one, assessed up to 10 days
Secondary	Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) 1 week after transplantation surgery	% of subjects with allergy to the components of the membrane or of the blood circuit (tube set) until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Blood transfusion rate before transplantation	% of subjects who received blood transfusion before transplantation	Before transplantation
Secondary	Blood transfusion rate during the transplantation surgery	% of subjects who received blood transfusion during the transplantation surgery	During the transplantation surgery
Secondary	Blood transfusion rate 1 week after transplantation surgery	% of subjects who received blood transfusion until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Occurrence rate of deep vein or graft vein thrombosis during the transplantation surgery	% of subjects with deep vein or graft vein thrombosis during the transplantation surgery	During the transplantation surgery
Secondary	Graft ablation rate 1 week after transplantation surgery	% of subjects with graft ablation until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Complication rate on surgical area 1 week after transplantation surgery	% of subjects with complication on the surgical area until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Infectious complication rate 1 week after transplantation surgery	% of subjects with Infectious complication until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Need for dialysis session(s) 1 week after transplantation surgery	number of subjects for which one or several dialysis session(s) is necessary until 1 week after transplantation surgery	1 week after transplantation surgery
Secondary	Graft rejection rate 1 month after transplantation surgery	% of subjects with graft rejection until 1 month after transplantation surgery	1 month after transplantation surgery
Secondary	Graft rejection rate 3 months after transplantation surgery	% of subjects with graft rejection until 3 months after transplantation surgery	3 months after transplantation surgery
Secondary	Graft rejection rate 6 months after transplantation surgery	% of subjects with graft rejection until 6 months after transplantation surgery	6 months after transplantation surgery
Secondary	Renal function 1 month after transplantation surgery	creatinine 1 month after transplantation surgery	1 month after transplantation surgery
Secondary	Renal function 3 months after transplantation surgery	creatinine 3 months after transplantation surgery	3 months after transplantation surgery
Secondary	Renal function 6 months after transplantation surgery	creatinine 6 months after transplantation surgery	6 months after transplantation surgery
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	plasma level of fibrinogen clotting factors	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	plasma level of factor XIII	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	plasma level of thrombin-antithrombin complex	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	plasma level of platelet secretion proteins (sCD40L, PF4)	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	plasma level of ADAMTS13 metalloprotease	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	Von Willebrand factor (cleaved form)	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	blood level of platelet-monocyte complexes	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	blood level of platelet-neutrophil polynuclear complexes	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	endogenous thrombin potential	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Secondary	Change in hemostasis parameters from before the desensitization protocol to after	peak thrombin	the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)