An International, Multicentre, Interventional, Randomised, Assessor-blinded Trial to MAXimise the METHotrexate Therapy Potential in Patients with Active Rheumatoid Arthritis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 182
- 试验地点
- 1
- 主要终点
- CDAI remission (≤2.8) at week 24
研究概览
简要总结
The MethMax trial is a prospective, international, multicentre, randomised, assessor-blinded, parallel-group, low intervention study. Patients with active rheumatoid arthritis treated with oral methotrexate up to 25mg weekly will be randomised in 50:50 fashion to receive 25mg oral vs subcutaneous methotrexate for the period of 24 weeks. In regular visits, patient reported outcomes, clinical disease activity, therapy adherence and diverse established and exploratory biomarkers will be assessed.
详细描述
Methotrexate is recommended as the first-line therapy in patients with rheumatoid arthritis. However, a significant proportion of patients does not achieve disease remission with methotrexate monotherapy, which can be attributed to multiple reasons. We hypothesize, that the efficacy limitations of this well-known medication can be, to some extent, overcome by sufficient dose and route optimisation. Furthermore, individual factors effecting the treatment response are unknown. Thus, we aim to evaluate the "maximised methotrexate therapy" before switching to biologic or targeted synthetic drugs.
The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, low-intervention trial, including 182 patients across 7 European countries. Patients with active rheumatoid arthritis, naïve to biologic or targeted synthetic antirheumatic drugs, who have been on a stable oral methotrexate therapy for the past 3 months will be randomised in 1:1 ratio to either 25mg oral or 25mg subcutaneous methotrexate weekly. In both arms, a short glucocorticoid therapy will be prescribed at baseline visit. The active study duration for each patient is 24 weeks. After inclusion, study visits take place at baseline, weeks 4, 8, 12, 16 and 24. The clinical efficacy and safety parameters will be obtained at each visit. At predefined timepoints, further patient reported outcomes, exploratory biomarkers like sweat and blood metabolites, as well as medication adherence will be assessed. Written consent will be obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and has recently started recruitment at the first centre.
The anticipated results will suggest whether the subcutaneous administration of 25mg methotrexate weekly is superior to oral methotrexate 25mg and lower doses in each route respectively. The outcomes include clinical disease activity, methotrexate metabolism analyses and medication adherence. The gained knowledge could lead to individual therapy optimisation and new therapy recommendations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
joint assessor blinding
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, ≥ 18 years of age, capable of understanding and signing an informed consent (including sufficient literacy and proficiency in the local language) and following the study procedures
- •Patients with rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria
- •Ongoing conventional therapy with oral methotrexate (between ≥10mg and 25mg weekly) for ≥3 months with stable dosing, and clinical and laboratory tolerance of this treatment for at least 12 weeks
- •CDAI > 2.8 + at least 1 clinically swollen joint (on 28-Joint count)
- •Willingness to increase methotrexate dosing and change the route of administration according to study procedures
排除标准
- •Inflammatory rheumatic diseases other than RA
- •Ongoing or previous therapy with any biological DiseaseModifying Anti-Rheumatic Drug (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) or conventional synthetic DMARDs (csDMARDs) other than methotrexate and hydroxychloroquine
- •Use of GC unless on stable oral dose ≤10mg for at least 4 weeks prior to study inclusion
- •Patients using NSAIDs, unless taken at a stable dose for ≥2 weeks prior to study inclusion
- •Intraarticular GC treatment in the last 8 weeks
- •Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator
- •Elevated liver enzymes (aspartate transaminase (ASAT) and/or alanine transaminase (ALAT)), and/or alkaline phosphatase (AP), and/or gamma-glutamyl transferase (GGT) above 2x the upper limit normal (ULN)
- •Reduced kidney function (glomerular filtration rate (GFR)<60)
- •Haematologic abnormalities (grade 2 or 3: anaemia, leukopenia, thrombocytopenia)
- •Stomatitis under the treatment with MTX
- •Known history of recurrent/serious infections in the previous two months (such as, but not limited to, hepatitis, pneumonia, or pyelonephritis)
- •A positive HBsAg and/or HCV test at screening visit
- •Ongoing or recurring opportunistic infections (e.g., herpes zoster, cytomegalovirus, pneumocystis, aspergillosis, histoplasmosis, or mycobacteria) as judged by the investigator
- •Women of childbearing potential without the use of adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) and willing to continue this precaution for the duration of the study until 6 months after receiving the last medication
- •Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease, as judged by the investigator
- •Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access
- •Being unwilling or unable to perform s.c injections
- •Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)
- •Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion
- •History of alcohol or substance abuse within the preceding 6 months
- •Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial
- •Immunisation with a live/attenuated vaccine within 12 weeks prior to baseline or potential need to receive a live vaccine during the course of the study
- •Active participation in any other interventional study
研究组 & 干预措施
methotrexate 25mg s.c.
methotrexate 25mg s.c. weekly dose
干预措施: Methotrexate (Drug)
methotrexate 25mg p.o.
methotrexate 25mg p.o. weekly dose
干预措施: Methotrexate (Drug)
结局指标
主要结局
CDAI remission (≤2.8) at week 24
时间窗: 24 weeks
The primary endpoint is the achievement of remission defined as the CDAI ≤2.8 assessed 24 weeks after randomisation comparing patients with dose/route optimization (≥10mg MTX oral weekly switched to 25mg MTX subcutaneously weekly) and oral dose optimization (≥10mg MTX oral weekly switched to 25mg MTX oral weekly).
次要结局
- CDAI low disease activity (≤10) at week 24(24 weeks)
- CDAI remission (≤2.8) at week 12(12 weeks)
- CDAI low disease activity (≤10) at week 12(12 weeks)
- ACR20% response at week 24(24 weeks)
- ACR20% response at week 12(12 weeks)
- ACR50% response at week 24(24 weeks)
- ACR50% response at week 12(12 weeks)
- ACR70% response at week 24(24 weeks)
- ACR70% response at week 12(12 weeks)
- Patient reported outcomes on NRS(12 weeks)
- Quality of Life questionnaires(12 weeks)
- Joint count and inflammatory markers(12 weeks)
研究者
Helga Lechner-Radner
Medical University of Vienna
Medical University of Vienna