Systematic Transplantectomy Versus Conventional Care After Kidney Graft Failure

NCT01817504 | Completed DMC

• 2 other identifiers: 2012.7142012-A00421-42
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 9

Brief 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control group, immunosuppression will be continued at the maintenance dose during the current surgical procedure, and withdrawn two weeks later,similary to systematic transplantectomy.

Conditions

Renal Transplantation

Keywords

Renal failure,; Transplantectomy; Immunosuppression; Sensitization

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Kinetics anti-HLA antibodies after transplantectomy

  12 months after inclusion

• Morbidity and mortality after transplantectomy

  12 months after inclusion

• Measuring the impact of systematic transplantectomy on mortality, inflammation, nutritional status, anemia, hypertension and cardiovascular risk factors

  12 months

• Infectious comorbidity

  12 months

• Costs of two strategies

  12 months after inclusion

Study Arms (2)

Study group

ACTIVE COMPARATOR

The study group corresponds to systematic transplantectomy under immunosuppressive therapy within two months after return to dialysis,

Procedure: Systematic transplantectomy

Control group

OTHER

The control group corresponds to progressive reduction of immunosuppression without systematic transplantectomy after return to dialysis

Procedure: Progressive reduction of immunosuppression

Interventions

Systematic transplantectomy PROCEDURE

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.

Study group

Progressive reduction of immunosuppression PROCEDURE

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.

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (9)

Service de Néphrologie et Transplantation Rénale, CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Service de Néphrologie -Dialyse-Transplantation, Hôpital Michallon

Grenoble, 38043, France

Location

Transplantation Department, Hôpital Edourad Herriot

Lyon, 69003, France

Location

Service de Néphrologie et Transplantation Rénale - Hôpital Lapeyronie

Montpellier, 34295, France

Location

Institut de Transplantation, Urologie et Néphrologie - CHU Nantes

Nantes, 44093, France

Location

Service de Néphrologie-Dialyse, Centre Hospitalier d'Annecy

Pringy, 74374, France

Location

Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord

Saint-Etienne, 42055, France

Location

Service de Néphrologie et Transplantation Rénale - Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Service de Néphrologie, Immunologie Clinique - CHU Bretonneau

Tours, 37044, France

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Emmanuel MORELON, MD

  Transplantation Department, Hopital Edouard Herriot, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2013
• First Posted: March 25, 2013
• Study Start: March 1, 2013
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: November 21, 2022

Record last verified: 2022-11

Locations

FR (9)