early active Rheumatoid Arthritis, previously untreated with DMARDS MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Ledertrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: methotrexate
CAS Number: 7413-34-5
Other descriptive name: METHOTREXATE DISODIUM
Concentration unit: mg milligram(s)
Concentra
Sponsors
University Hospitals Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - Diagnosis of RA as defined by the 1987-revised ACR classification criteria or the new ACR/Eular 2010 criteria for early RA - Early RA defined by a disease duration of = 1 year - Use of a reliable method of contraception for women of childbearing potential - Able and willing to give written informed consent and participate in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Previous treatment with methotrexate or leflunomide - Previous treatment with cyclophosfamide, azathioprine or cyclosporine - Previous treatment with sulphasalazine for more than 3 weeks - Previous treatment with hydroxychloroquine for more than 6 weeks - Previous treatment with corticoids or intra-articular glucocorticoïds within 4 weeks before treatment start or for more than 4 weeks - Previous treatment with an investigational drug for the treatment/prevention of RA - Contraindications for corticosteroids - Contraindications for methotrexate, sulphasalazine or leflunomide ? known chronic hepatic disease (alcoholic, fibrosis, …) ? known pulmonary interstitial disease or fibrosis ? known chronic renal failure ? history of malignant neoplasm within 5 years ? hematologic problems at the discretion of the investigator - Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study - Pregnancy, breastfeeding or no use of a reliable method of contraception - Alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study in patients with severe RA, the efficacy and effectiveness of a classic COBRA scheme (with 15mg MTX) versus two modified COBRA schemes respectively “slim” (without SSZ and with half dose steroids) and “avant-garde” (leflunomide instead of SSZ and half dose steroids) in daily practice. To study in patients with less severe RA, the daily practice efficacy and effectiveness of a tight step up regimen (with 15mg MTX) versus a modified COBRA slim scheme (without SSZ and with half dose steroids). ;Secondary Objective: A superiority analysis will be performed: in the high risk arm, COBRA classic and COBRA avant-garde vs. COBRA slim and in the low risk arm, COBRA slim vs. Tight Step Up.;Primary end point(s): • Proportion in remission (DAS28CRP < 2.6) ;Timepoint(s) of evaluation of this end point: at week 16, 52 and 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Disease activity: – Proportion good EULAR responders – Proportion of patients in remission according to the SDAI (score = 3,3). – Proportion of patients in remission according to the CDAI (score = 2 ,8). – Proportion of patients in remission according to the preliminary Boolean ACR/EULAR criteria. – Proportion of patients in remission according to DAS28CRP 0,22) – Proportion HAQ = 0 • X-ray (Sharp Vanderheijde score) Effectiveness: • Proportion of treatment failures due to efficacy/effectiveness problems • Proportion with unplanned treatment changes (steroids and DMARDs) • Proportion lost from follow up • Total cumulative steroid dose / mean steroid dose per day • Proportion started on biologics Safety: number / type of (serious) adverse events;Timepoint(s) of evaluation of this end point: at 16 weeks, 52 weeks and 104 weeks | — |
Countries
Belgium
Contacts
Public ContactPatrick Verschueren
University Hospitals Leuven
Outcome results
None listed