PMID- 29247107 OWN - NLM STAT- MEDLINE DCOM- 20180802 LR - 20190202 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 7 IP - 12 DP - 2017 Dec 14 TI - 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. PG - e018748 LID - 10.1136/bmjopen-2017-018748 [doi] LID - e018748 AB - 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/m(2) 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. CI - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. FAU - Furuta, Shunsuke AU - Furuta S AD - Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan. FAU - Sugiyama, Takao AU - Sugiyama T AD - Department of Rheumatology, Shimoshizu Hospital, National Hospital Organisation, Yotsukaido, Japan. FAU - Umibe, Takeshi AU - Umibe T AD - Department of Internal Medicine, Matsudo City Hospital, Matsudo, Japan. FAU - Kaneko, Yuko AU - Kaneko Y AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medical, Tokyo, Japan. FAU - Amano, Koichi AU - Amano K AD - Department of Rheumatology and Clinical Immunology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan. FAU - Kurasawa, Kazuhiro AU - Kurasawa K AD - Centre for Rheumatic Diseases, Dokkyo Medical University, Tochigi, Japan. FAU - Nakagomi, Daiki AU - Nakagomi D AD - Third Department of Internal Medicine, University of Yamanashi, Chuo, Japan. FAU - Hiraguri, Masaki AU - Hiraguri M AD - Department of Internal Medicine, Narita Red Cross Hospital, Narita, Japan. FAU - Hanaoka, Hideki AU - Hanaoka H AD - Clinical Research Center, Chiba University Hospital, Chiba, Japan. FAU - Sato, Yasunori AU - Sato Y AD - Biostatistics, Graduate School of Medicine, Chiba University, Chiba, Japan. FAU - Ikeda, Kei AU - Ikeda K AD - Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan. FAU - Nakajima, Hiroshi AU - Nakajima H AD - Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan. CN - LoVAS Trial study investigators LA - eng SI - ClinicalTrials.gov/NCT02198248 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20171214 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Glucocorticoids) RN - 0 (Immunosuppressive Agents) RN - 4F4X42SYQ6 (Rituximab) RN - 9PHQ9Y1OLM (Prednisolone) SB - IM EIN - BMJ Open. 2018 Jan 21;8(1):e018748corr1. PMID: 29358455 MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*drug therapy MH - Dose-Response Relationship, Drug MH - Drug Therapy, Combination MH - Female MH - Glucocorticoids/*administration & dosage MH - Humans MH - Immunosuppressive Agents/*administration & dosage MH - Japan MH - Male MH - Prednisolone/*administration & dosage MH - Remission Induction MH - Research Design MH - Rituximab/*administration & dosage MH - Treatment Outcome PMC - PMC5778278 OTO - NOTNLM OT - clinical pharmacology OT - rheumatology COIS- Competing interests: HN reports receiving grant support from Chugai Pharmaceutical Corporation (Roche group). FIR - Nagashima, Kengo IR - Nagashima K FIR - Kagami, Shin-Ichiro IR - Kagami SI FIR - Kashiwakuma, Daisuke IR - Kashiwakuma D FIR - Watanabe, Hiroshi IR - Watanabe H FIR - Motojima, Shinji IR - Motojima S FIR - Nakashita, Tamao IR - Nakashita T FIR - Kobayashi, Yoshihisa IR - Kobayashi Y FIR - Matsumura, Ryutaro IR - Matsumura R FIR - Oya, Yoshihiro IR - Oya Y FIR - Kita, Yasuhiko IR - Kita Y FIR - Wada, Yoko IR - Wada Y FIR - Narita, Ichiei IR - Narita I FIR - Ogawa, Noriyoshi IR - Ogawa N FIR - Suzuki, Daisuke IR - Suzuki D FIR - Kono, Hajime IR - Kono H FIR - Uchida, Shunya IR - Uchida S FIR - Fujigaki, Yoshihide IR - Fujigaki Y FIR - Hiromura, Keiju IR - Hiromura K FIR - Sakairi, Toru IR - Sakairi T FIR - Owada, Takayoshi IR - Owada T FIR - Kawashima, Hirotoshi IR - Kawashima H FIR - Matsuki, Ayako IR - Matsuki A FIR - Yamagata, Mieko IR - Yamagata M FIR - Ohta, Yuichiro IR - Ohta Y FIR - Sakai, Ryota IR - Sakai R FIR - Ishii, Tomonori IR - Ishii T FIR - Kawakami, Atsushi IR - Kawakami A FIR - Sumida, Takayuki IR - Sumida T FIR - Watanabe, Norihiko IR - Watanabe N FIR - Yasuda, Shinsuke IR - Yasuda S FIR - Kumanogoh, Atsushi IR - Kumanogoh A FIR - Kohsaka, Hitoshi IR - Kohsaka H FIR - Tanaka, Yoshiya IR - Tanaka Y FIR - Komatsuda, Atsushi IR - Komatsuda A FIR - Shimojima, Yoshihiro IR - Shimojima Y FIR - Sekigawa, Iwao IR - Sekigawa I FIR - Hanaoka, Hironari IR - Hanaoka H FIR - Makino, Yuichi IR - Makino Y FIR - Yoshimi, Ryusuke IR - Yoshimi R FIR - Hayashi, Taichi IR - Hayashi T FIR - Otani, Hiroshi IR - Otani H EDAT- 2017/12/17 06:00 MHDA- 2018/08/03 06:00 PMCR- 2017/12/14 CRDT- 2017/12/17 06:00 PHST- 2017/12/17 06:00 [entrez] PHST- 2017/12/17 06:00 [pubmed] PHST- 2018/08/03 06:00 [medline] PHST- 2017/12/14 00:00 [pmc-release] AID - bmjopen-2017-018748 [pii] AID - 10.1136/bmjopen-2017-018748 [doi] PST - epublish SO - BMJ Open. 2017 Dec 14;7(12):e018748. doi: 10.1136/bmjopen-2017-018748.