Evaluation of Immunosuppressive Therapy Discontinuation Versus Maintenance in ANCA-Associated Vasculitis with End-Stage Renal Disease: A Randomized Multicenter Trial

The primary objective of this clinical trial is to evaluate the **superiority** of discontinuing immunosuppressive therapy in patients with ANCA vasculitis and end-stage renal disease (ESRD) compared to continuing standard maintenance immunosuppressive therapy. The focus is on assessing severe prejudicial event-free survival over a 24-month period. This is clinically relevant as it aims to determine whether stopping immunosuppressive treatment can lead to better patient outcomes in terms of survival without severe adverse events, which is crucial for improving the management of patients with ESRD and ANCA vasculitis.

The clinical trial involves participants diagnosed with **ANCA vasculitis** and **End-stage Renal disease**. The study population includes both male and female subjects, aged between 18 and 90 years. Participants are required to have a renal injury associated with either Granulomatosis with Polyangiitis (GPA) or Microscopic Polyangiitis (MPA) and must be experiencing either an initial manifestation or a relapse of the condition. Additionally, participants must have End-stage Renal Disease, characterized by a glomerular filtration rate of 15 mL/min or less, or a requirement for dialysis for more than 60 days. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to have given written informed consent and be affiliated with the French social security system. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of discontinuing **immunosuppressive** therapy in patients with ANCA vasculitis and end-stage renal disease (ESRD) compared to standard maintenance therapy. This is a prospective, multicenter, randomized, open-label trial. The study aims to demonstrate the superiority of immunosuppression discontinuation in terms of severe prejudicial event-free survival over a 24-month period. The trial will involve adult participants aged 18 to 90 years who have been diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) with renal involvement and meet specific inclusion criteria, such as having ESRD defined by a glomerular filtration rate of ≤15 mL/min or requiring dialysis for more than 60 days.

The trial will commence with a screening visit to confirm eligibility, during which informed consent will be obtained. Participants will then be randomized into either the discontinuation group or the standard maintenance group. The trial will include regular follow-up visits to monitor the participants' health status and any adverse events. The primary endpoint is the time from randomization to the first severe prejudicial event, such as severe infection, major AAV relapse, or death, within the 24-month follow-up period. Secondary endpoints will be assessed as well, although they are not specified in the provided data.

Participants are expected to be involved in the study for the entire 24-month duration unless they experience a severe prejudicial event or choose to withdraw consent. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any medical condition that, in the opinion of the investigator, would make continued participation detrimental to the participant's health. The trial is not categorized as low intervention and is classified under therapeutic use clinical trials. The estimated recruitment start date was February 1, 2018, with an estimated end date of March 14, 2031.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. **Azathioprine** is utilized in two forms: as a pharmaceutical form coded PHF00170MIG and as a tablet under the brand name Imurel 25 mg. Both forms are administered orally with a maximum daily dose of 2 mg/kg. The treatment period for the PHF00170MIG form is up to 24 months, while the Imurel 25 mg tablet is administered for up to 2 months. Azathioprine is classified under the ATC code L04AX01 and is used as an immunosuppressive agent.

**Mycophenolate mofetil** is administered as Mycophenolate mofetil Tillomed 500 mg film-coated tablets. These tablets are purple-colored, capsule-shaped, and film-coated, administered orally with a maximum daily dose of 2 grams. The treatment period is up to 2 months. Mycophenolate mofetil is classified under the ATC code L04AA06, indicating its role as an immunosuppressive agent.

**Prednisone** is provided as CORTANCYL 20 mg, comprimé sécable, administered orally with a maximum daily dose of 20 mg. The treatment period is up to 3 months. Prednisone is classified under the ATC code H02AB07 and serves as an immunosuppressive agent.

**Rituximab** is administered as an injectable solution with a maximum daily dose of 500 mg. The treatment period is up to 6 months. Rituximab is classified under the ATC code L01XC02 and is used as an immunosuppressive agent.

**Mycophenolic acid** is administered in a pharmaceutical form coded PHF00170MIG, with a maximum daily dose of 2 grams, and the treatment period extends up to 24 months. It is classified under the ATC code L04AA06 and is used as an immunosuppressive agent.

**Prednisolone** is administered in a pharmaceutical form coded PHF00245MIG, with a maximum daily dose of 20 mg, and the treatment period extends up to 24 months. It is classified under the ATC code H02AB07 and is used as an anti-inflammatory agent.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the efficacy and safety of these treatments in patients with ANCA vasculitis and end-stage renal disease.

Efficacy in the clinical trial will be assessed by evaluating the primary endpoint, which is the time between randomization and the first occurrence of a severe prejudicial event. These events include severe infection, major relapse of **ANCA vasculitis**, or death, monitored over a 24-month follow-up period. The trial aims to demonstrate the superiority of discontinuing immunosuppression in patients with end-stage renal disease associated with ANCA vasculitis compared to standard maintenance immunosuppressive therapy. The assessment will involve tracking the occurrence of these severe events from the point of randomization throughout the study duration. The data collected will be analyzed to determine the efficacy of the treatment strategy in prolonging event-free survival in the patient population.