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

• ClinicalTrials.gov Identifier: NCT02523768
• Recruitment Status: Active, not recruiting
• First Posted: August 14, 2015
• Last Update Posted: July 23, 2020
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Tracking Information

• First Submitted Date: August 4, 2015
• First Posted Date: August 14, 2015
• Last Update Posted Date: July 23, 2020
• Actual Study Start Date: January 2011
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2015)

• clinical recurrence [ Time Frame: 5 years ]
  onset of proteinuria 1g / j and / or microalbuminuria greater than 300 mg / day
• histological recurrence [ Time Frame: 5 years ]
  histological recurrence defined by the presence of mesangial deposits of IgA (at least 1+) by immunofluorescence on a biopsy of the graft

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Glomerulonephritis
• IgAN

Intervention

• Drug: ATG-F
• Drug: Simulect

Study Arms

• 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
  Intervention: 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).
  Intervention: Drug: Simulect

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 19, 2016): 115
• Original Estimated Enrollment (submitted: August 13, 2015): 212
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02523768
• Other Study ID Numbers: 0908143; 2009-018189-36 ( EudraCT Number ); A100405-32 ( Other Identifier: AFSSAPS )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• Study Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Not Provided

Investigators

• Principal Investigator: Francois BERTHOUX, MD PhD; CHU de SAINT-ETIENNE

• PRS Account: Centre Hospitalier Universitaire de Saint Etienne
• Verification Date: July 2020