Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis (LoVAS): protocol for a multicentre, open-label, randomised controlled trial

• Published in: BMJ open 2017-12, Vol.7 (12), p.e018748-e018748
• Main Authors: Furuta, Shunsuke, Sugiyama, Takao, Umibe, Takeshi, Kaneko, Yuko, Amano, Koichi, Kurasawa, Kazuhiro, Nakaomi, Daiki, Hiraguri, Masaki, Hanaoka, Hideki, Sato, Yasunori, Ikeda, Kei, Nakajima, Hiroshi
• Format: Article
• Language: English
• Subjects: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - drug therapy; Arthritis; Cytoplasm; Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzymes; Evidence-based medicine; Female; Glucocorticoids - administration & dosage; Humans; Immunoassay; Immunosuppressive Agents - administration & dosage; Immunotherapy; Japan; Male; Monoclonal antibodies; Mortality; Neutrophils; Prednisolone - administration & dosage; Remission (Medicine); Remission Induction; Research Design; Rheumatology; Rituximab - administration & dosage; Treatment Outcome
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2017-018748

IntroductionAntineutrophil cytoplasm antibody-associated vasculitis (AAV) is a form of systemic vasculitis. The current standard induction therapy with the combination of high-dose glucocorticoids and cyclophosphamide or rituximab has high remission rates of 80%–90%. However, it is also associated with various side effects, including death due to infection or cardiovascular disease. There is an unmet medical need of a new therapy to reduce side effects.Methods and analysisThis is a phase IV multicentre, open-label, randomised controlled trial that aims to evaluate the efficacy and safety of a new remission induction regimen with the combination of low-dose glucocorticoids and rituximab. Newly diagnosed patients with AAV will be assessed for eligibility at 34 tertiary rheumatology/nephrology centres in Japan. One hundred and forty patients will be randomised (1:1) to receive low-dose prednisolone (0.5 mg/kg daily) plus rituximab (375 mg/m2 weekly) or high-dose prednisolone (1 mg/kg daily) plus rituximab. The trial consists of remission induction and maintenance phases. The primary endpoint of the study is the remission rate at 6 months (induction phase). Relapse and long-term safety profile will also be assessed until 24 months (maintenance phase).Ethics and disseminationThe protocol was first approved by the Institutional Review Board of Chiba University Hospital (reference number: G25051), and then approved by each participating site. The trial was registered at the University hospital Medical Information Network (UMIN) clinical registry (UMIN000014222) and ClinicalTrials.gov registry (NCT02198248). The Low-dose Glucocorticoid Vasculitis Induction Study (LoVAS) trial is currently ongoing and is due to finish in September 2019. The findings of this trial will be disseminated to participants through peer-reviewed publications and presented at national and international conferences in accordance with the Consolidated Standards of Reporting Trials (CONSORT) Statement.Trial registration numberUMIN000014222; NCT02198248.