Clinical trial NCT03323476: Maintaining or Stopping Immunosuppressive Therapy in Patients With ANCA Vasculitis and End-stage Renal Disease
Official title: Maintaining or Stopping Immunosuppressive Therapy in Patients With ANCA Vasculitis and End-stage Renal Disease: a Prospective, Multicenter, Randomized, Open-label, Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
End Stage Renal Disease
Lead sponsor: Centre Hospitalier Departemental Vendee
Sponsor class: OTHER
First posted: 2017-10-27
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: During the 24 months of follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire Amiens
city: Angers
country: France
facility: CHU Angers
city: Angoulême
country: France
facility: Centre Hospitalier Angoulême
city: Arras
country: France
facility: Centre Hospitalier ARRAS
city: Avignon
country: France
facility: Centre Hospitalier Avignon
city: Avranches
country: France
facility: AUB Santé
city: Besançon
country: France
facility: CHRU Besançon
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire Bordeaux
city: Boulogne-sur-Mer
country: France
facility: Centre Hospitalier Boulogne sur Mer
city: Bourges
country: France
facility: Centre Hospitalier Jacques Coeur
city: Brest
country: France
facility: Centre Hospitalier Universitaire de Brest
city: Cergy-Pontoise
country: France
facility: Centre Hospitalier René Dubois - Pontoise
city: Chartres
country: France
facility: Centre Hospitalier Chartres
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire G. Montpied
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble
city: La Roche sur yon
country: France
facility: Centre Hospitalier Départemental Vendée
city: La Rochelle
country: France
facility: Centre Hospitalier La Rochelle
city: Le Mans
country: France
facility: Centre ECHO - Le Mans
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Le Puy-en-Velay
country: France
facility: Centre Hospitalier Emile ROUX
city: Lille
country: France
facility: Hôpital Privé La Louvière
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Dupuytren
city: Lorient
country: France
facility: AUB Santé - Lorient
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marseille
country: France
facility: Hopital de la Conception - APHM
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier de Mont de Marsan
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire Lapeyronie
city: Mulhouse
country: France
facility: GHR Mulhouse Sud Alsace
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Nice
country: France
facility: Centre Hospitalier Universitaire Nice
city: Nimes
country: France
facility: CHU de Nimes
city: Paris
country: France
facility: Aphp - Bichat
city: Paris
country: France
facility: Aphp - Hegp
city: Paris
country: France
facility: APHP - Henri Mondor
city: Paris
country: France
facility: CHU Kremlin - Bicêtre
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire Poitiers
city: Quimper
country: France
facility: Centre Hospitalier Quimper
city: Rennes
country: France
facility: AUB Santé - Rennes
city: Rennes
country: France
facility: Centre Hospitalier Universitaire Rennes
city: Rouen
country: France
facility: Centre Hospitalier Universitaire Rouen
city: Saint Nazaire
country: France
facility: Centre Hospitalier Saint-Nazaire
city: Saint-Brieuc
country: France
facility: Centre Hospitalier Saint Brieuc
city: Saint-Malo
country: France
facility: Centre Hospitalier Saint-Malo
city: Saint-Étienne
country: France
facility: Centre Hospitalier Universitaire Saint Etienne
city: Sallanches
country: France
facility: Centre Hospitalier Alpes Léman
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Toulouse
country: France
facility: Clinique Saint Exupéry
city: Tours
country: France
facility: CHRU Bretonneau
city: Valenciennes
country: France
facility: Centre Hospitalier Valenciennes
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique
city: Évreux
country: France
facility: CHI Eure Seine
Study officials:
affiliation: CHD Vendée
name: Grégoire COUVRAT-DESVERGNES
role: PRINCIPAL_INVESTIGATOR
References: