TNF-blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs in Early Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— NEO-RACo  

Official title:

Use of TNF-blocking Therapy in Combination With DMARDs in Patients With Early Rheumatoid Arthritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00908089
• Other study ID #: NEO-RACo
• Status: Active, not recruiting
• Phase: Phase 4
• First received: May 22, 2009
• Last updated: March 31, 2015
• Start date: March 2003
• Est. completion date: December 2015

Study information

• Verified date: March 2015
• Source: Helsinki University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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
• 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

Locations

Country	Name	City	State
Finland	Hämeenlinna Central Hospital	Hämeenlinna
Finland	Rheumatism Foundation Hospital	Heinola
Finland	Helsinki University Central Hospital	Helsinki
Finland	Orton Invalid Foundation Hospital	Helsinki
Finland	Jyväskylä Central Hospital	Jyväskylä
Finland	Kuopio University Hospital	Kuopio
Finland	Lappeenranta Central Hospital	Lappeenranta
Finland	Oulu University Hospital	Oulu
Finland	Satakunta Central Hospital	Rauma
Finland	Rovaniemi Central Hospital	Rovaniemi
Finland	Seinäjoki Central Hospital	Seinäjoki
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku

Sponsors (12)

Lead Sponsor	Collaborator
Helsinki University	Central Hospital of Kanta-Hame, Jyväskylä Central Hospital, Kuopio University Hospital, Lappi Central Hospital, Orton Invalid Foundation, Oulu University Hospital, Rheumatism Foundation Hospital, Satakunta Central Hospital, Seinajoki Central Hospital, South Karelia central hospital, University of Turku

Country where clinical trial is conducted

Finland, 

References & Publications (3)

Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppänen O, Luosujärvi R, Luukkainen R, Karjalainen A, Blåfield H, Uutela T, Ilva K, Julkunen HA, Paimela L, Puolakka K, Moilanen E, Hannonen PJ, Möttönen T; NEO-RACo Study Group — View Citation

Rantalaiho V, Kautiainen H, Järvenpää S, Korpela M, Malmi T, Hannonen P, Kaipiainen-Seppänen O, Yli-Kerttula T, Möttönen T, Mustila A, Karjalainen A, Paimela L, Uutela T, Leirisalo-Repo M; NEO-RACo Study Group. Failure in longterm treatment is rare in act — View Citation

Rantalaiho V, Kautiainen H, Korpela M, Hannonen P, Kaipiainen-Seppänen O, Möttönen T, Kauppi M, Karjalainen A, Laiho K, Laasonen L, Hakola M, Peltomaa R, Leirisalo-Repo M; NEO-RACo Study Group. Targeted treatment with a combination of traditional DMARDs p — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HAQ	Health assessment questionnaire(HAQ)	1, 2, 3, 4 and 5 years	No
Other	Work disability	Permanent work disability	2, 3, 4 and 5 years	No
Other	Good response	Number of patients with sustained good response (>=ACR50%) from month 3 till the end of study	5 years	No
Other	Number of arthroplasties	Cumulative number of arthroplasties at 5 years	5 years	No
Other	Direct and indirect costs	Cumulative direct an indirect costs at 5 years	5 years	No
Other	Adverse events	Monitoring of safety and adverse events	10 years	Yes
Other	ACR Remission		10 years	No
Other	DAS28 remission		2, 3, 4, 5, 7 and10 years	No
Other	HAQ	Health assessment questionnaire (HAQ)	10 years	No
Other	Work disability	Cumulative permanent work disability up till 10 years	10 years	No
Other	Number of arthroplasties	Cumualite number of arthroplasties by 10 years	10 years	No
Other	Direct and indirect costs	Cumulative direct and indirect costs by 10 years	10 years	No
Other	Radiology (erosions)	radiologic changes in hands and feet	10 years	No
Primary	Remission by ACR criteria		2 years	No
Secondary	Radiology (erosions)		2 years	No
Secondary	Sustained remission	Number of patients with sustained ACR remission from month 3 till the end of the study	2 years	No
Secondary	Costs	Cumulative direct and indirect costs at 2 years	2	No