Clinical trial NCT02523768: Prevention in Recipients With Primary IgA Nephropathy of Recurrence After Kidney Transplantation: ATG-F Versus Basiliximab as Induction Immunosuppressive Treatment
Official title: Prevention in Recipients With Primary IgA Nephropathy of Recurrence After Kidney Transplantation: ATG-F Versus Basiliximab as Induction Immunosuppressive Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Glomerulonephritis
IgAN
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2015-08-14
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: IgA nephropathy (IgAN) is a histologically defined glomerulonephritis (renal biopsy) by the presence of deposits immunoglobulin A (IgA) in the renal mesangium (at least 1+) by immunofluorescence. The clinic allows excluding secondary forms (10-15%). Recurrence of this condition on the renal graft is time-dependent and confirmed in 25 to 50% of 10 years post-transplant.

The primary immunosuppressive induction regimens currently used in kidney transplantation are the anti-lymphocyte globulin (GAL) whose main target is human T lymphocytes (ATG, polyclonal) and monoclonal anti-CD25 antibodies (α chain of the interleukin receptor 2 in the surface of T lymphocytes). Due to their potent and prolonged immunosuppressive properties, the ATG may prevent or delay the recurrence on renal transplant.

The aim of this study was to evaluate the influence of induction therapy (ATG versus Basiliximab) in the cumulative incidence at 5 years of (IgAN) recurrence after a first kidney transplant.

This is a prospective, multicenter, randomized, open trial with a follow-up period of 5 years old.

Patients in the ATG arm will receive 5 antilymphocyte globulin infusions Fresenius® (rabbit immunoglobulin antilymphocyte human T-Fresenius® said ATG) from Day 0 to Day + 4 post-transplant (day 0 one dose of 4mg / kg, day 1 one dose of 4mg/kg, day2 one dose of 4mgkg, day 3 one dose of 3 m/kg and day 4 and one final dose of 3 mg/kg) and the patients in the anti-CD25 arm will receive 2 doses of 20 mg of basiliximab (Simulect®) pn day 0 and day 4 after the graft. The maintenance immunosuppressive therapy is left to the discretion of the center.

The primary endpoint will be the clinical and histological recurrence of IgAN defined by the presence of mesangial deposits of IgA (at least 1) by immunofluorescence on a biopsy of the graft triggered by the onset of proteinuria 1g/j and/or microalbuminuria greater than 300 mg / day.


Eligibility criteria: Inclusion Criteria:

* Free, informed, express and written.
* Diagnosis of native kidney primary IgA glomerulonephritis biopsy-proven
* First kidney transplantation (one kidney)

Exclusion Criteria:

* Panel Reactive Antibody (PRA PRA global or class I or class II PRA) over 50% on a serum before transplantation
* Multi-organ graft
* Transplants using donor limits or sub-optimal: donor age ≥ 70 years, donors in the study BIGRAS or taken heart beating donors (tested on computer infusion) or other restriction factors
* IgA glomerulonephritis secondary to HSP (Henoch-Schonlein purpura) or Systemic Lupus Erythematosus (SLE) or alcoholic cirrhosis
* History of cancer older than 5 years or with advanced cancer, but except for non-recurrent skin cancers
* Infectious diseases scalable: tuberculosis, HIV, Hepatitis B virus or Hepatitis C virus infection with viral replication and / or chronic hepatitis
* Allergy to rabbit proteins
* Severe thrombocytopenia (\<50,000 platelets/ul)
* Bacterial infection, viral and fungal uncontrolled therapeutically
* Pregnancy or lactation

Primary outcomes:
measure: clinical recurrence
timeFrame: 5 years
measure: histological recurrence
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHU de BESANCON
city: Bordeaux
country: France
facility: CHU de BORDEAUX
city: Le Kremlin Bicetre
country: France
facility: Chu Kremlin Bicetre
city: Lyon
country: France
facility: Hopital Edouard HERRIOT
city: Montpellier
country: France
facility: CHU de MONTPELLIER
city: Nancy
country: France
facility: CHU de NANCY
city: Nantes
country: France
facility: CHU de NANTES
city: Nice
country: France
facility: CHU de NICE
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Paris
country: France
facility: Hopital Tenon
city: Pierre Benite
country: France
facility: Hopital LYON Sud
city: Saint-etienne
country: France
facility: CHU de SAINT-ETIENNE
city: Strasbourg
country: France
facility: CHU de STRASBOURG
city: Toulouse
country: France
facility: CHU de TOULOUSE
city: Tours
country: France
facility: CHRU de TOURS
Study officials:
affiliation: CHU de SAINT-ETIENNE
name: Francois BERTHOUX, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: