Use of Tumor Necrosis Factor (TNF) - Blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs (DMARDs) in Early Rheumatoid Arthritis (NEO-RACo)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The FIN-RACo trial is an investigator initiated multicenter (n=15 centers in Finland) prospective study on the treatment of patients with early rheumatoid arthritis (RA) with combination therapy with disease modifying antirheumatic drugs starting with methotrexate, sulphasalazine, hydroxychloroquine and prednisolone (COMBI). During the first 6 months, the patients are randomized to treatment with infliximab/placebo added on the combination treatment. The study is prospective for 5 years, with extension to 10 years. The target is to induce remission in both treatment arms. To reach this target, the investigators use frequent changes of doses and anti-rheumatic drugs and use of intra-articular glucocorticoid injections. The primary endpoints are the proportions of patients with remission at 2 and 5 years in both treatment arms.
| Condition | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Drug: methotrexate, sulfasalazine, hydroxychloroquine + infliximab Drug: methotrexate, sulfasalazine, hydroxychloroquine + placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Use of TNF-blocking Therapy in Combination With DMARDs in Patients With Early Rheumatoid Arthritis |
- Remission by ACR criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Radiology (erosions) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Sustained remission [ Time Frame: 2 years ] [ Designated as safety issue: No ]Number of patients with sustained ACR remission from month 3 till the end of the study
- Costs [ Time Frame: 2 ] [ Designated as safety issue: No ]Cumulative direct and indirect costs at 2 years
- HAQ [ Time Frame: 1, 2, 3, 4 and 5 years ] [ Designated as safety issue: No ]Health assessment questionnaire(HAQ)
- Work disability [ Time Frame: 2, 3, 4 and 5 years ] [ Designated as safety issue: No ]Permanent work disability
- Good response [ Time Frame: 5 years ] [ Designated as safety issue: No ]Number of patients with sustained good response (>=ACR50%) from month 3 till the end of study
- Number of arthroplasties [ Time Frame: 5 years ] [ Designated as safety issue: No ]Cumulative number of arthroplasties at 5 years
- Direct and indirect costs [ Time Frame: 5 years ] [ Designated as safety issue: No ]Cumulative direct an indirect costs at 5 years
- Adverse events [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]Monitoring of safety and adverse events
| Enrollment: | 100 |
| Study Start Date: | March 2003 |
| Estimated Study Completion Date: | December 2015 |
| Primary Completion Date: | May 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 3 DMARDs + infliximab
Combination therapy with 3 DMARDs (starting with methotrexate, sulphasalazine and hydroxychloroquine)+ Prednisolon + infliximab (for 6 months)
|
Drug: methotrexate, sulfasalazine, hydroxychloroquine + infliximab
methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, infliximab 3 mg/kg during first 6 months
Other Name: Trexan, Salazopyrin EN, Oxiklorin, Remicade
|
|
Placebo Comparator: 3 DMARDs + placebo
Combination therapy with 3 DMARDs (starting with methotrexate, sulphasalazine and hydroxychloroquine)+ Prednisolon + placebo (for 6 months)
|
Drug: methotrexate, sulfasalazine, hydroxychloroquine + placebo
methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, placebo infusion during first 6 months
Other Name: Trexan, Salazopyrin EN, Oxiklorin, 0.9% NaCl
|
Detailed Description:
We want to study, whether early treatment with infliximab for 6 months started parallel with the combination therapy of methotrexate, sulphasalazine, hydroxychloroquine and prednisolone (COMBI) can induce quick remission in patients with early RA, if the remission can be sustained after 6 months on patients continuing the COMBI treatment and can diminish the risk of progression of erosive changes in patients with early RA, and if we can reduce costs of the 2 treatment arms with respect to costs due to the disease.
100 patients with early RA will be included in the study. The patients are randomised into COMBI + placebo or into COMBI +infliximab.
All patients are treated openly with COMBI, starting with a combination of methotrexate, sulfasalazine, hydroxychloroquine and prednisolone. In addition, the patients are randomized into a) infliximab or b) similar placebo. The COMBI treatment will be continued for 2 years, but the infliximab/placebo will be given only during the first 6 months.
The patients will be evaluated clinically at week 0, 4, 6, 10, 14, 18, 22 and 26 (at the day of infusion, prior to the infusion) and at months 8, 10, 12, 15, 18, 21, and 24 and at annually thereafter till 10 years.
If a patient has adverse events due to individual drugs in the COMBI, the treatment can be substituted by another DMARD.The disease activity will be measured according to the ACR core set of disease activity.
Radiology of hands (PA projection) and feet (PA projection) at baseline and at 1, 2, 3, 4, 5, 7 and 10 years. We also will record sick leaves, loss of income, and work disability.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of RA fulfilling the ACR classification criteria for RA
- Patients within age group of 18-60 years
- Patients not permanently work disabled or retired
- Duration of symptoms < 12 months, and who have not received DMARD previously
- Patients with active disease (see below)
Criteria for active disease at entry:
- > 6 swollen joints (66 joint count)
- > 6 tender joints (68 joint count)
- duration of early morning stiffness > 45 min and/or ESR > 30 mm/h and/or CRP > 20 mg/l
Exclusion Criteria:
- Previous treatment with DMARDs
- Previous treatment with oral glucocorticoids during the previous 6 months
- Less than 30 days from previous intra-articular injection with corticosteroids
- Allergy to sulphonamides
- Allergy to acetylsalicylic acid
- Allergy to methotrexate
- Allergy to antimalarials
- Previous treatment with biologicals
- Serum creatinine value > upper limit of normal (registered in 2 different blood samples)
- Serum transaminase levels > 2x upper limit of normal (registered in 2 different samples)
- Known/previous malignancy excluding basalioma or in situ cervical cancer >5 years previously
- Cardiac failure (NYHA III-IV)
- Previous history of tuberculosis and/or exposition to tuberculosis and/or typical changes of previous/active tuberculosis in chest radiology
- Active infection
- Pregnancy
- Leukopenia (WBC < 4 x 109/l)
- Thrombocytopenia (platelets < 100 x 109/l)
- Active peptic ulcer
- Type I or type II diabetes under poor control
- Heavy use of alcohol
- Fertile women not practising contraception or who are planning pregnancy
- Male patients wishing to have children during the therapy
- Other autoimmune rheumatic disease
- Other chronic disease which judged by the physician could influence the patient's compliance or intervene the study course
- Patient is not cooperative
Contacts and Locations| Finland | |
| Rheumatism Foundation Hospital | |
| Heinola, Finland, FI-18120 | |
| Helsinki University Central Hospital | |
| Helsinki, Finland, FI-00029 HUS | |
| Orton Invalid Foundation Hospital | |
| Helsinki, Finland, FI-00280 | |
| Hämeenlinna Central Hospital | |
| Hämeenlinna, Finland, FI-13530 | |
| Jyväskylä Central Hospital | |
| Jyväskylä, Finland, FI-40620 | |
| Kuopio University Hospital | |
| Kuopio, Finland, FI-703211 | |
| Lappeenranta Central Hospital | |
| Lappeenranta, Finland, FI-53130 | |
| Oulu University Hospital | |
| Oulu, Finland, FI-90029 OYS | |
| Satakunta Central Hospital | |
| Rauma, Finland, FI-26100 | |
| Rovaniemi Central Hospital | |
| Rovaniemi, Finland, FI-96100 | |
| Seinäjoki Central Hospital | |
| Seinäjoki, Finland, FI-60220 | |
| Tampere University Hospital | |
| Tampere, Finland, FI-33521 | |
| Turku University Central Hospital | |
| Turku, Finland, FI-21540 | |
| Study Director: | Marjatta Leirisalo-Repo, MD, Prof | Helsinki University |
| Study Chair: | Timo Möttönen, MD, Prof | Turku University |
| Study Chair: | Markku Korpela, MD, PhD | Tampere University |
| Study Chair: | Riitta Luosujärvi, MD, PhD | Helsinki University Central Hospital |
| Study Chair: | Oili Kaipiainen-Seppänen, MD, PhD | Kuopio University Hospital |
| Study Chair: | Markku Kauppi, MD, PhD | Rheumatism Foundation Hospital |
More Information
No publications provided
| Responsible Party: | Marjatta Leirisalo-Repo, MD, PhD, Prof, Helsinki University |
| ClinicalTrials.gov Identifier: | NCT00908089 History of Changes |
| Other Study ID Numbers: | NEO-RACo |
| Study First Received: | May 22, 2009 |
| Last Updated: | January 13, 2013 |
| Health Authority: | Finland: Finnish Medicines Agency |
Keywords provided by Helsinki University:
|
rheumatoid arthritis methotrexate sulfasalazine hydroxychloroquine infliximab |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Infliximab Antirheumatic Agents Hydroxychloroquine Methotrexate Sulfasalazine Therapeutic Uses Pharmacologic Actions |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Antineoplastic Agents Dermatologic Agents Folic Acid Antagonists |
ClinicalTrials.gov processed this record on May 22, 2013