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

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.

Study Overview

• Status: Terminated
• Conditions: Glomerulonephritis; IgAN
• Intervention / Treatment: Drug: ATG-F; Drug: Simulect

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25000
    • CHU de Besancon
  • Bordeaux, France, 33000
    • CHU de Bordeaux
  • Le Kremlin Bicetre, France, 94275
    • CHU Kremlin Bicetre
  • Lyon, France, 69000
    • Hôpital Edouard Herriot
  • Montpellier, France, 34000
    • CHU de Montpellier
  • Nancy, France, 54000
    • CHU de Nancy
  • Nantes, France, 44000
    • CHU de Nantes
  • Nice, France, 06000
    • Chu de Nice
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75013
    • Hopital Pitie Salpetriere
  • Pierre Benite, France, 69310
    • Hôpital Lyon Sud
  • Saint-etienne, France, 42000
    • Chu de Saint-Etienne
  • Strasbourg, France, 67000
    • CHU de Strasbourg
  • Toulouse, France, 31000
    • CHU de Toulouse
  • Tours, France, 37000
    • CHRU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: ATG-F
Active Comparator: 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).	Drug: Simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical recurrence	onset of proteinuria 1g / j and / or microalbuminuria greater than 300 mg / day	5 years
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Francois BERTHOUX, MD PhD, Chu de Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2011
• Primary Completion (Actual): January 24, 2020
• Study Completion (Actual): February 24, 2020

Study Registration Dates

• First Submitted: August 4, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Recurrence; Glomerulonephritis; Glomerulonephritis, IGA; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab
• Other Study ID Numbers: 0908143; 2009-018189-36 (EudraCT Number); A100405-32 (Other Identifier: AFSSAPS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No