Clinical trial NCT03477656: Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Transplantation
Keywords: ABO incompatible kidney transplantation
Desensitization
Double Filtration PlasmaPherisis (DFPP)
Specific immunoadsorption
Living donor kidney transplantation
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2018-03-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Success rate
timeFrame: the day of transplantation
Secondary outcomes:
measure: Differential cost-efficacy ratio of support for patients receiving a live donor kidney transplant Incompatible ABO and benefiting from a desensitization procedure
timeFrame: 7 months
measure: Surgical complication rate during the desensitization sessions
timeFrame: From the first desensitization session to the last one, assessed up to 10 days
measure: Surgical complication rate during the transplantation surgery
timeFrame: During the transplantation surgery
measure: Thrombotic complication rate during the desensitization sessions
timeFrame: From the first desensitization session to the last one, assessed up to 10 days
measure: Thrombotic complication rate 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Rate of bleeding and/or hematoma on vascular access during the desensitization sessions
timeFrame: From the first desensitization session to the last one, assessed up to 10 days
measure: Rate of hematoma occurrence during the transplantation surgery
timeFrame: During the transplantation surgery
measure: Rate of occurrences of hemorrhage away from vascular access during the desensitization sessions
timeFrame: From the first desensitization session to the last one, assessed up to 10 days
measure: Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions
timeFrame: From the first desensitization session to the last one, assessed up to 10 days
measure: Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Blood transfusion rate before transplantation
timeFrame: Before transplantation
measure: Blood transfusion rate during the transplantation surgery
timeFrame: During the transplantation surgery
measure: Blood transfusion rate 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Occurrence rate of deep vein or graft vein thrombosis during the transplantation surgery
timeFrame: During the transplantation surgery
measure: Graft ablation rate 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Complication rate on surgical area 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Infectious complication rate 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Need for dialysis session(s) 1 week after transplantation surgery
timeFrame: 1 week after transplantation surgery
measure: Graft rejection rate 1 month after transplantation surgery
timeFrame: 1 month after transplantation surgery
measure: Graft rejection rate 3 months after transplantation surgery
timeFrame: 3 months after transplantation surgery
measure: Graft rejection rate 6 months after transplantation surgery
timeFrame: 6 months after transplantation surgery
measure: Renal function 1 month after transplantation surgery
timeFrame: 1 month after transplantation surgery
measure: Renal function 3 months after transplantation surgery
timeFrame: 3 months after transplantation surgery
measure: Renal function 6 months after transplantation surgery
timeFrame: 6 months after transplantation surgery
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
measure: Change in hemostasis parameters from before the desensitization protocol to after
timeFrame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital Toulouse (Hospital Rangueil)
Study officials:
affiliation: University Hospital of Toulouse
name: Arnaud DEL BELLO, MD
role: PRINCIPAL_INVESTIGATOR
References: