Can low-dose methotrexate reduce effusion-synovitis and symptoms in patients with mid- to late-stage knee osteoarthritis? Study protocol for a randomised, double-blind, and placebo-controlled trial
Zhaohua Zhu,
Qinghong Yu,
Xiaomei Leng,
Weiyu Han,
Zhanguo Li,
Cibo Huang,
Jieruo Gu,
Yi Zhao,
Kang Wang,
Tianwang Li,
Yifang Mei,
Jianhua Xu,
Zhiyi Zhang,
David Hunter,
Flavia Cicuttini,
Xiaofeng Zeng,
Changhai Ding
Affiliations
Zhaohua Zhu
Clinical Research Centre, Zhujiang Hospital, Southern Medical University
Qinghong Yu
Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University
Xiaomei Leng
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Weiyu Han
Clinical Research Centre, Zhujiang Hospital, Southern Medical University
Zhanguo Li
Department of Rheumatology & Immunology, Peking University People’s Hospital
Cibo Huang
Department of Rheumatology, Beijing Hospital, National Center of Gerontology
Jieruo Gu
Department of Rheumatology, 3rd Affiliated Hospital of Sun Yet-Sen University Guangzhou
Yi Zhao
Department of Rheumatology & Allergy, Xuanwu Hospital, Capital Medical University
Kang Wang
Department of Rheumatology, the First Affiliated Hospital of Anhui Medical University
Tianwang Li
Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital
Yifang Mei
Department of Rheumatology, the First Affiliated Hospital of Harbin Medical University
Jianhua Xu
Department of Rheumatology, the First Affiliated Hospital of Anhui Medical University
Zhiyi Zhang
Department of Rheumatology, the First Affiliated Hospital of Harbin Medical University
David Hunter
Clinical Research Centre, Zhujiang Hospital, Southern Medical University
Flavia Cicuttini
Department of Epidemiology and Preventive Medicine, Monash University
Xiaofeng Zeng
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Changhai Ding
Clinical Research Centre, Zhujiang Hospital, Southern Medical University
Abstract Background Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA. Methods/design This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed. Discussion If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life. Trial registration ClinicalTrials.gov NCT03815448 . Registered on 21 January 2019.
