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TNF-blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified March 2015 by Marjatta Leirisalo-Repo, Helsinki University.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00908089
First Posted: May 25, 2009
Last Update Posted: April 1, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
Central Hospital of Kanta-Hame
Information provided by (Responsible Party):
Marjatta Leirisalo-Repo, Helsinki University
  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: Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab Drug: Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 Marjatta Leirisalo-Repo, Helsinki University:

Primary Outcome Measures:
  • Remission by ACR criteria [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • Radiology (erosions) [ Time Frame: 2 years ]
  • Sustained remission [ Time Frame: 2 years ]
    Number of patients with sustained ACR remission from month 3 till the end of the study

  • Costs [ Time Frame: 2 ]
    Cumulative direct and indirect costs at 2 years


Other Outcome Measures:
  • HAQ [ Time Frame: 1, 2, 3, 4 and 5 years ]
    Health assessment questionnaire(HAQ)

  • Work disability [ Time Frame: 2, 3, 4 and 5 years ]
    Permanent work disability

  • Good response [ Time Frame: 5 years ]
    Number of patients with sustained good response (>=ACR50%) from month 3 till the end of study

  • Number of arthroplasties [ Time Frame: 5 years ]
    Cumulative number of arthroplasties at 5 years

  • Direct and indirect costs [ Time Frame: 5 years ]
    Cumulative direct an indirect costs at 5 years

  • Adverse events [ Time Frame: 10 years ]
    Monitoring of safety and adverse events

  • ACR Remission [ Time Frame: 10 years ]
  • DAS28 remission [ Time Frame: 2, 3, 4, 5, 7 and10 years ]
  • HAQ [ Time Frame: 10 years ]
    Health assessment questionnaire (HAQ)

  • Work disability [ Time Frame: 10 years ]
    Cumulative permanent work disability up till 10 years

  • Number of arthroplasties [ Time Frame: 10 years ]
    Cumualite number of arthroplasties by 10 years

  • Direct and indirect costs [ Time Frame: 10 years ]
    Cumulative direct and indirect costs by 10 years

  • Radiology (erosions) [ Time Frame: 10 years ]
    radiologic changes in hands and feet


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: Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab
Combination therapy with 3 DMARDs (starting with methotrexate 10-25 mg/week, sulphasalazine 1-2 g/day and hydroxychloroquine 35 mg/kg/week)+ Prednisolon 7.5 mg/day + infliximab 3 mg/kg at weeks 4, 6, 10, 18, 26
Drug: Trexan+Salazopyrin+Oxiklorin+prednisolone + infliximab
methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, prednisolone 7.5 mg/day, and infliximab 3 mg/kg during first 6 months
Other Name: Trexan, Salazopyrin, Oxiklorin, Prednison, Remicade
Placebo Comparator: Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo
Combination therapy with 3 DMARDs (starting with methotrexate 10-25 mg/week, sulphasalazine 1-2 g/day and hydroxychloroquine 25 mg/kg/week)+ Prednisolon 7.5 mg/day + placebo at weeks 4, 6, 10, 18, 26
Drug: Trexan+Salazopyrin+Oxiklorin+prednisolone + placebo
methotrexate 10-25 mg/week, sulfasalazine 1-2 g/day, hydroxychloroquine 35 mg/kg/week, prednisolone 7.5 mg/day, and placebo infusion during first 6 months
Other Name: Trexan, Salazopyrin, Oxiklorin, Prednison, 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. After 2 years, if the patient is in remission, the prednisolone will be gradually tapered off. If the patient is still in remission, the conventional DMARDs can be sequentially tapered down. If the remission is lost, the last DMARD is reinstituted. If the patient is not in remission of COMBI, after 26 weeks, treatments are free, including the institution of a biological drug.

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 adverse events, sick leaves, loss of income, costs, and work disability.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Central Hospital of Kanta-Hame
Investigators
Study Director: Marjatta Leirisalo-Repo, MD, Prof Helsinki University
Study Chair: Timo Möttönen, MD, Prof University of Turku
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 Päijänne Tavastia Central Hospital
  More Information

Publications:

Responsible Party: Marjatta Leirisalo-Repo, MD, PhD, Prof, Helsinki University
ClinicalTrials.gov Identifier: NCT00908089     History of Changes
Other Study ID Numbers: NEO-RACo
First Submitted: May 22, 2009
First Posted: May 25, 2009
Last Update Posted: April 1, 2015
Last Verified: March 2015

Keywords provided by Marjatta Leirisalo-Repo, 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
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Naltrexone
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents