Prevention in Recipients With Primary IgA Nephropathy of Recurrence After Kidney Transplantation: ATG-F Versus Basiliximab as Induction Immunosuppressive Treatment

NCT ID: NCT02523768

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-08
• Study Completion Date: 2020-02-24

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.

Conditions

Glomerulonephritis; IgAN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ATG-F

The ATG-Fresenius® is administered by slow infusion over four hours after antihistamine (2 bulbs Polaramine® IV) and intravenous methylprednisolone (minimum 30mg); it is started on day 0 prior to surgery at doses of 4 mg / kg, and then continued to day 1, day 2 to 4mg / kg, then day 3, day 4 at the dose of 3 mg / kg

Group Type: EXPERIMENTAL

ATG-F

Intervention Type: DRUG

Simulect

The anti CD25 (basiliximab, Simulect®) is administered intravenously before surgery of renal transplantation (Day 0 and Day + 4 (1 ampoule of 20 mg x 2 times).

Group Type: ACTIVE_COMPARATOR

Simulect

Intervention Type: DRUG

Interventions

ATG-F

Intervention Type: DRUG

Simulect

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francois BERTHOUX, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CHU de SAINT-ETIENNE

Locations

CHU de BESANCON

Besançon, , France

CHU de BORDEAUX

Bordeaux, , France

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, , France

Hopital Edouard HERRIOT

Lyon, , France

CHU de MONTPELLIER

Montpellier, , France

CHU de NANCY

Nancy, , France

CHU de NANTES

Nantes, , France

CHU de NICE

Nice, , France

Hopital Pitie Salpetriere

Paris, , France

Hopital Tenon

Paris, , France

Hopital LYON Sud

Pierre-Bénite, , France

CHU de SAINT-ETIENNE

Saint-Etienne, , France

CHU de STRASBOURG

Strasbourg, , France

CHU de TOULOUSE

Toulouse, , France

CHRU de TOURS

Tours, , France

Countries

France

Other Identifiers

2009-018189-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A100405-32

Identifier Type: OTHER

Identifier Source: secondary_id

0908143

Identifier Type: -

Identifier Source: org_study_id