Use of Tumor Necrosis Factor (TNF) - Blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs (DMARDs) in Early Rheumatoid Arthritis (NEO-RACo)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Seinajoki Central Hospital
Oulu University Hospital
Jyväskylä Central Hospital
Kuopio University Hospital
Satakunta Central Hospital
University of Turku
Rheumatism Foundation Hospital
Orton Invalid Foundation
South Carelia Central Hospital
Lappi Central Hospital
Kanta-Häme Central Hospital
Information provided by (Responsible Party):
Marjatta Leirisalo-Repo, Helsinki University
ClinicalTrials.gov Identifier:
NCT00908089
First received: May 22, 2009
Last updated: January 13, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


Further study details as provided by Helsinki University:

Primary Outcome Measures:
  • Remission by ACR criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00908089

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
Sponsors and Collaborators
Helsinki University
Seinajoki Central Hospital
Oulu University Hospital
Jyväskylä Central Hospital
Kuopio University Hospital
Satakunta Central Hospital
University of Turku
Rheumatism Foundation Hospital
Orton Invalid Foundation
South Carelia Central Hospital
Lappi Central Hospital
Kanta-Häme Central Hospital
Investigators
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
Methotrexate
Infliximab
Hydroxychloroquine
Sulfasalazine
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal

ClinicalTrials.gov processed this record on September 18, 2014