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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
  1. Shunsuke Furuta1,
  2. Takao Sugiyama2,
  3. Takeshi Umibe3,
  4. Yuko Kaneko4,
  5. Koichi Amano5,
  6. Kazuhiro Kurasawa6,
  7. Daiki Nakaomi7,
  8. Masaki Hiraguri8,
  9. Hideki Hanaoka9,
  10. Yasunori Sato10,
  11. Kei Ikeda1,
  12. Hiroshi Nakajima1
  13. on behalf of the LoVAS Trial study investigators
    1. 1 Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan
    2. 2 Department of Rheumatology, Shimoshizu Hospital, National Hospital Organisation, Yotsukaido, Japan
    3. 3 Department of Internal Medicine, Matsudo City Hospital, Matsudo, Japan
    4. 4 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medical, Tokyo, Japan
    5. 5 Department of Rheumatology and Clinical Immunology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan
    6. 6 Centre for Rheumatic Diseases, Dokkyo Medical University, Tochigi, Japan
    7. 7 Third Department of Internal Medicine, University of Yamanashi, Chuo, Japan
    8. 8 Department of Internal Medicine, Narita Red Cross Hospital, Narita, Japan
    9. 9 Clinical Research Center, Chiba University Hospital, Chiba, Japan
    10. 10 Biostatistics, Graduate School of Medicine, Chiba University, Chiba, Japan
    1. Correspondence to Dr Shunsuke Furuta; shfuruta{at}gmail.com

    Abstract

    Introduction Antineutrophil 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 analysis This 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 dissemination The 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 number UMIN000014222; NCT02198248.

    • rheumatology
    • clinical pharmacology

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Contributors All authors made significant contribution to the conception and design of the study protocol. SF designed the original concept and wrote the study protocol and manuscript. The protocol and manuscript was critically reviewed by TS, TU, YK, KA, KK, DN, MH, HH, KI and HN. YS wrote the statistical analysis plan. SF is the coordinating investigator and HN is the chief investigator of this study. All authors gave approval for the publication.

    • Funding This trial was funded by intramural competitive grant of Chiba University Hospital for Clinical Research.

    • Disclaimer Chugai Pharmaceutical Corporation was not involved in the planning of the protocol or in the conduct of the trial.

    • Competing interests HN reports receiving grant support from Chugai Pharmaceutical Corporation (Roche group).

    • Ethics approval The protocol was firstly approved by the Institutional Review Board of Chiba University Hospital (reference number: G25051), and then approved by each participating site.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators See online appendix.

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