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

Glomerulonephritis Clinical Trial

— PIRAT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02523768
• Other study ID #: 0908143
• Secondary ID: 2009-018189-36A1
• Status: Terminated
• Phase: Phase 4
• Start date: January 8, 2011
• Est. completion date: February 24, 2020

Study information

• Verified date: January 2021
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 117
• Est. completion date: February 24, 2020
• Est. primary completion date: January 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis, IGA
• IgAN
• Recurrence

Intervention

Drug:
• ATG-F

• Simulect

Locations

Country	Name	City	State
France	CHU de BESANCON	Besancon
France	CHU de BORDEAUX	Bordeaux
France	Chu Kremlin Bicetre	Le Kremlin Bicetre
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 Benite
France	CHU de SAINT-ETIENNE	Saint-etienne
France	CHU de STRASBOURG	Strasbourg
France	CHU de TOULOUSE	Toulouse
France	CHRU de TOURS	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinical recurrence	onset of proteinuria 1g / j and / or microalbuminuria greater than 300 mg / day	5 years
Primary	histological recurrence	histological recurrence defined by the presence of mesangial deposits of IgA (at least 1+) by immunofluorescence on a biopsy of the graft	5 years