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

Study Overview
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Brief Summary
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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.

Official Title
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Maintaining or Stopping Immunosuppressive Therapy in Patients With ANCA Vasculitis and End-stage Renal Disease: a Prospective, Multicenter, Randomized, Open-label, Clinical Trial

Conditions
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Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, End Stage Renal Disease

Intervention / Treatment
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* Other: Discontinuation (or not initiation) of Immunosuppressive Therapy
* Drug: Maintenance (or initiation) of immunosuppressive treatment: Imurel®, Mabthera®,Cellcept®, Cortancyl®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Discontinuation of maintenance treatment<br> | Other: Discontinuation (or not initiation) of Immunosuppressive Therapy<br>* Discontinuation (or not initiation) of Immunosuppressive Therapy<br>|
| Active Comparator: Maintenance of immunosuppressive treatment<br> | Drug: Maintenance (or initiation) of immunosuppressive treatment: Imurel®, Mabthera®,Cellcept®, Cortancyl®<br>* Maintenance (or initiation) of Immunosuppressive Therapy: Imurel®, Mabthera®,Cellcept®, Cortancyl®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point will be the time between inclusion and the first severe prejudicial event (measured in days) during 24 months of follow-up. | Severe prejudicial event is defined by the occurrence of: severe infection, major AAV relapse, death | During the 24 months of follow-up |