Maintaining or Stopping Immunosuppressive Therapy in Patients With ANCA Vasculitis and End-stage Renal Disease (MASTER-ANCA)

Centre Hospitalier Departemental Vendee

Status and phase

Enrolling

Phase 3

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

End Stage Renal Disease

Treatments

Drug: Maintenance (or initiation) of immunosuppressive treatment: Imurel®, Mabthera®,Cellcept®, Cortancyl®

Other: Discontinuation (or not initiation) of Immunosuppressive Therapy

Study type

Interventional

Funder types

Other

Identifiers

NCT03323476

CHD005-17

Details and patient eligibility

About

This prospective randomized trial aims to evaluate the feasibility, risk and benefit of the discontinuation of immunosuppressive maintenance treatments in AAV (Antineutrophil Cytoplasmic Autoantibodies (ANCA)-associated vasculitis) patients who have reached ESRD (end-stage renal disease). Our hypothesis is that discontinuation of immunosuppressive therapy in AAV patients with ESRD will not expose these patients to an excessive risk of extra-renal AAV relapse, while reducing the rate of complications due to immunosuppression, particularly infections.

Patients with ESRD related to AAV will be randomized into 2 arms:

arm 1: discontinuation (or not initiation) of maintenance treatment (Experimental group) arm 2: maintenance (or initiation) of immunosuppressive treatment (Control group).

The main objective of this study is to demonstrate a superiority of immunosuppression discontinuation in ESRD-AAV patients compared to standard maintenance immunosuppressive therapy in terms of severe prejudicial event-free survival at 24 months. The second objectives include the frequency of major and minor relapses, of infectious episodes and leukopenia in both groups and the establishment of a prospective database regarding the outcome of ESRD-AAV patients.

Enrollment

136 estimated patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥ 18 years and ≤ 90 years
Patients affected by a GPA or MPA AAV with a renal injury
Patients with initial manifestation or relapse of AAV
Patients with ESRD, defined by a glomerular filtration rate estimated using the MDRD formula ≤15 mL/min or requirement for dialysis for more than 60 days
Patients with ESRD on native kidney
Patients who gave written informed consent for participation in the study
Patients with affiliation to the French social security system

Exclusion criteria

Patients who experienced severe extra-renal disease due to AAV (intra-alveolar haemorrhage with blood oxygen saturation ≤ 85% on room air or ventilated, or central nervous system disease) in the last 12 months prior to inclusion
Patients with AAV-associated renal involvement (with active inflammatory lesions in kidney biopsy) diagnosed less than three months and receiving induction treatment with cyclophosphamide or rituximab or diagnosed less than 45 days for patients who have receveid only treatment based on steroid infusion without cyclophosphamide or rituximab
Patients who received maintenance immunosuppressive treatment for more than 6 months during the last 12 months
Patient with a diagnosis of vasculitis other than GPA or MPA
Patients with another immunologic systemic disease (Lupus, sarcoidosis...) Patients with active HCV, HBV or HIV infection
Patients with a history of serious viral infection (CMV, HHV8, etc.) in the 2 months prior to the inclusion, or severe uncontrolled chronic infection (tuberculosis, etc.)
Patients with uncontrolled cancer or hemopathy
Kidney transplant patient
Inability to understand and sign the informed consent
Pregnant women.
Women of child-bearing age without effective method of contraception
Age < 18 years or > 90 years.
Patients under guardianship or trusteeship.