Systematic Transplantectomy Versus Conventional Care After Kidney Graft Failure

Renal Transplantation Clinical Trial

— DESYRE  

Official title:

Interest of Systematic Transplantectomy Versus Conventional Care After Kidney Graft Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01817504
• Other study ID #: 2012.714
• Secondary ID: 2012-A00421-42
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: November 2021

Study information

• Verified date: November 2022
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Our hypothesis is early and systematic transplantectomy under a well-conducted immunosuppression is associated with a decreased risk of anti-HLA immunization against a conservative attitude including a gradual reduction of immunosuppression, with or without a transplantectomy performed for cause (clinical event).

Observation or Investigation Method Used :

The study is :

• multicenter

• prospective

• open

• randomized: patients are divided into two parallel groups:

• study group: transplantectomy within six weeks after return to dialysis, antiproliferatives stop at the start of dialysis, Maintenance anticalcineurin-based-immunosuppression without dose reduction up to two weeks after transplantectomy. Abrupt discontinuation of anticalcineurin two weeks after transplantectomy. Corticosteroids: 5mg per day until one month after transplantectomy then stop within one month.

• control group: No systematic transplantectomy. Antiproliferatives stop at the start of dialysis.Anticalcineurins half dose for 3 months, ¼ dose for 3 months and then stop. Corticosteroids:5 mg per day for 6 months, and then tapered and stop within 3 months.

In the case of transplantectomy for cause in the control group, immunosuppression will be continued at the maintenance dose during the current surgical procedure, and withdrawn two weeks later,similary to systematic transplantectomy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 2021
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age = 18 Years.

• Patients affiliated to health protection system, social security in France or any similar regimen.

• Renal transplant patient with end-stage transplantation, regardless of the number of previous transplants.

• Patient receiving immunosuppressive protocol based on anticalcineurin or mTOR inhibitors

• Patient should have resume hemodialysis within 4 weeks

• Duration of transplantation more than one year

• Patient with asymptomatic graft

• immunogenic potential residual >50% (calculated PIR during the re-dialysis)

• Patient not covered by any measure of legal protection.

Exclusion Criteria:

• Immunogenic potential residual <50%

• Graft infection uncontrolled by treatment

• Active infectious pathology

• Inflammatory graft

• Uncontrolled arterial hypertention

• Inflammatory syndrome of undetermined origin with CRP>50mg/l

• Fever of unknown origin for more than 8 days T>38°C

• Contra-indication to surgery

• AVK treatment

• Patient candidate for a living donor within 12 months

• Monotherapy with calcineurin inhibitors or mTOR inhibitors

• Treatment directed against the humoral response in the 6 months preceding the recovery of dialysis (Rituximab IV-Ig or high doses)

• Presence of another transplant (pancreas, liver, heart, lung)

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Procedure:
• Systematic transplantectomy
Transplantectomy within two months after return to dialyse. Antiproliferatives stop at the start of dialysis. Maintenance basic immunosuppressive treatment without dose reduction up to two weeks after transplantectomy. Abrupt discontinuation of the basic immunosuppressive treatment ttwo weeks after transplantectomy. Maintenance corticosteroids at 5mg per day until one month after transplantectomy then stop corticosteroids within one month.
• Progressive reduction of immunosuppression
Progressive reduction of immunosuppression. Transplantectomy for cause only. Antiproliferatives withdrawn at the start of dialysis. Maintenance of anticalcineurin or mTOR inhibitors half dose for 3 months, ¼ dose for 3 months and then stop. Maintenance corticosteroids for 6 months up to 5 mg per day, and then soft stop in 3 months. In case of transplantectomy by reason in the control group, basic immunosuppression will be continued at the maintenance dose during the current surgical procedure, and withdrawn two weeks later, similary to the strategy used in the study group.

Locations

Country	Name	City	State
France	Service de Néphrologie et Transplantation Rénale, CHU Gabriel Montpied	Clermont-Ferrand Cedex
France	Service de Néphrologie -Dialyse-Transplantation, Hôpital Michallon	Grenoble Cedex
France	Transplantation Department, Hôpital Edourad Herriot	Lyon
France	Service de Néphrologie et Transplantation Rénale - Hôpital Lapeyronie	Montpellier
France	Institut de Transplantation, Urologie et Néphrologie - CHU Nantes	Nantes
France	Service de Néphrologie-Dialyse, Centre Hospitalier d'Annecy	Pringy
France	Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord	Saint-Etienne
France	Service de Néphrologie et Transplantation Rénale - Nouvel Hôpital Civil	Strasbourg
France	Service de Néphrologie, Immunologie Clinique - CHU Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti HLA Immunization assessed by Luminex assay	Evaluate the interest of a transplantectomy early (<2 months after return to dialysis) and systematic under immunosuppressive in renal transplant patients after loss of renal graft function in terms of anti-HLA immunization (measured by Luminex test) a year after loss of renal graft function and return to dialysis in the renal transplant patient.; Proportion of patients who developed HLA immunization (DSA)after systematic transplantectomy under immunosuppression versus progressive reduction of immunosuppression without transplantectomy	12 months (M12)
Secondary	Kinetics anti-HLA antibodies after transplantectomy	Determine the kinetics of new onset anti-HLA antibodies at D0, D15, D30, M3, M6, M9 after systematic or for cause transplantectomy and in the year following graft failure and the proportion of immunized patients during the first 6 months after dialysis. HLA antibodies will be assessed by Luminex test. The specificity of antibodies against HLA I or HLA II will be determined, as well as Mean Immunofluorescence Intensity in each case.	12 months after inclusion
Secondary	Morbidity and mortality after transplantectomy	Determine the morbidity and mortality after transplantectomy according to its indication, systematic or for cause (transplantectomy indications in the control group: persistent pain graft, unexplained fever, hematuria, inflammation or unexplained anemia ).	12 months after inclusion
Secondary	Measuring the impact of systematic transplantectomy on mortality, inflammation, nutritional status, anemia, hypertension and cardiovascular risk factors	The following parameters will be measured at D0, M1, M3, M6, M9 and M12 after return to dialysis during the first year after kidney graft failure: CRP, pre-albuminemia, albuminemia, BMI, hemoglobin, hematocrit, blood pressure, cholesterol, LDL cholesterol and triglyceride.	12 months
Secondary	Infectious comorbidity	The impact of early cessation of immunosuppression on infectious complications after kidney graft failure will assessed. For each patient, origin of infection, bacterial, viral, fungal, will determined. The total number of infection episodes during the first year will be analyzed in the two groups.	12 months
Secondary	Costs of two strategies	To evaluate the medico-economic impact of each conservation strategy in the management of patients who return to dialysis	12 months after inclusion