Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis (RITUXGOPRO)
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|ClinicalTrials.gov Identifier: NCT03920722|
Recruitment Status : Not yet recruiting
First Posted : April 19, 2019
Last Update Posted : April 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Microscopic Polyangiitis (MPA)||Drug: Rituximab Drug: placebo||Phase 3|
Microscopic polyangiitis (MPA), is a small-sized vessel necrotizing vasculitis associated with anti-neutrophils cytoplasmic antibody (ANCA). Treatment of ANCA associated vasculitis (AAV) was previously based on glucocorticoids (GC) and cyclophosphamide. It has been demonstrated in two prospective randomized trials that rituximab is as effective as cyclophosphamide in the induction treatment of GPA and severe MPA. In addition, it was shown in GPA and MPA that rituximab is superior to azathioprine as maintenance therapy.
Patients with MPA without poor prognosis factor (Five factor score (FFS)=0) have not been included in the previous studies and GC alone is considered as the reference treatment in these patients. However, as much as 50% of these patients experience relapses after a 24 months follow-up and only 40% of patients have a long lasting remission.
In the group of patients with MPA without any poor prognosis factor (FFS=0), an additional treatment with rituximab might decrease the relapse rate from 40% to 15% after an 18 months' follow-up. The efficacy and safety of this proposal must be tested.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||106 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||March 2023|
Experimental regimen: One year Glucocorticoid treatment and Rituximab IV 1 gram on Day 1 and 15
1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine
Placebo Comparator: Rituximab-Placebo
Standard regimen: One-year Glucocorticoid treatment and Placebo-Rituximab IV on Day 1 and 15
Placebo-Rituximab 1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine
- Disease free survival rate [ Time Frame: 18 months ]
Failure free survival in patients with microscopic polyangiitis treated with rituximab and glucocorticoids compared to glucocorticoids alone.
- Primary failure: Vasculitis requiring a modification of immunosuppressive treatment or prednisone tapering protocol before M3
- Remission is defined by the absence of sign attributable to vasculitis and a Birmingham Vasculitis Activity Score (BVAS)=0 at M3
- Relapse is defined after visit M3 by a BVAS>0 or the impossibility to decrease glucocorticoids according to the predefined protocol. Therefore, patients who experience a primary failure or fail to enter remission or relapse will be considered as treatment failure.
- Cumulative dose of GC in each group [ Time Frame: 18 months ]GC dose will be recorded at each visit
- Proportion of patients who achieve a complete remission defined by the absence of sign attributable to vasculitis and a BVAS=0 [ Time Frame: 1 month ]Absence of sign attributable to vasculitis and a BVAS=0 at M3
- Compare proportion of patients who relapse and time to first relapse [ Time Frame: 18 months ]Relapse is defined after visit M3 by the reoccurrence of signs or symptoms attributable to vasculitis and a BVAS≥1 or the impossibility to decrease GC therapy according to the predefined protocol
- Among patients who relapse, proportion of major relapses [ Time Frame: 18 months ]Major relapse is defined by reappearance or worsening of disease with a BVAS≥1 and involvement of at least one major organ, a life-threatening manifestation, or both
- Among patients who relapse, proportion of minor relapses [ Time Frame: 18 months ]Minor relapse is defined by reappearance or worsening of disease with a BVAS≥1, not corresponding to a major relapse
- Mortality rate [ Time Frame: 18 months ]Proportion will be compared between groups
- Quality of life:Short Form Health Survey Questionnaire (SF-36) [ Time Frame: 18 months ]Assessed by mean variation of the SF-36 The 36-Item Short Form Health Survey questionnaire (SF-36) questionnaire includes 36 items related to eight health component (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health.) A scale has been established for each component and results vary from 0 (bad health perception) to 100 (good health perception).
- Disability [ Time Frame: 18 months ]Assessed by the mean variation of the Health Assessment Questionnaire (HAQ) Health Assessment Questionnaire (HAQ) is a questionnaire that evaluates the disability of the patient. Results vary from 0 (no assistance is needed) to 3 (patient usually needs both a special device and help from another person).
- Disability [ Time Frame: 18 months ]Assessed by the mean variation of the Euroqol 5D (EQ-5D). The EuroQol-5 dimension (EQ-5D-3L) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D is made up of five dimensions (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression), each of which can be rated at one of three levels (no problem, some problems, extreme/severe problems). The EuroQol questionnaire also contains a visual analogue scale (EQ-VAS), where patients are asked to rate their current health state on a 0 (worst imaginable health state) to 100 (best imaginable health state) scale.
- Severity of sequels linked to vasculitis as [ Time Frame: 18 months ]Assessed by comparison of the VDI score. The Vascular Damage index score documents any organ damage that has occurred in patients since the onset of vasculitis. The score includes 64 items that are categorized into 11 groups (by organ system) and result is the summ of each damaged items.
- Proportion of patients who still receive GC at the end of follow-up [ Time Frame: 18 months ]Proportion will be compared between groups
- Number and severity of side effect. [ Time Frame: 18 months ]Record of adverse events and serious adverse events related to vasculitis or treatment in each group. Classification is made according to the CTCAE toxicity grading system.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03920722
|Contact: Alexis REGENT, MD||+33 1 58 41 14 email@example.com|
|Contact: Alexandra BRUNEAU||+33 1 58 41 12 firstname.lastname@example.org|
|Study Chair:||Luc Mouthon, MD PhD||Assistance Publique - Hôpitaux de Paris|