Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis Clinical Trial

— ACUTE-JIA  

Official title:

Comparison of Anti-TNF Therapy Plus Methotrexate, Combination Therapy of DMARDs, and Methotrexate Alone in Very Early Polyarticular Juvenile Idiopathic Arthritis. A National Randomized Multicenter Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01015547
• Other study ID #: 211864, 318/E0/2002
• Secondary ID: 211864
• Status: Completed
• Phase: Phase 3
• First received: November 17, 2009
• Last updated: October 13, 2015
• Start date: May 2003
• Est. completion date: December 2013

Study information

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

Clinical Trial Summary

The objective of this study is to compare in very early polyarticular juvenile idiopathic arthritis (JIA) the efficacy, safety, and cost-benefit-ratio of three treatment strategies: biologic combination, combination of conventional disease-modifying drugs (DMARDs), and methotrexate alone.

Description:

DMARD-naive polyarticular JIA patients with an early disease (onset less than 6 months) are randomized into one of three treatment strategies: (1) biological combination, i.e., anti-TNF therapy with infliximab plus methotrexate; (2) Combination of DMARDs with methotrexate, sulfasalazine, plus hydroxychloroquine; and (3) Methotrexate alone.

The efficacy is evaluated by American College of Rheumatology Pediatric (ACR Pedi) criteria based on 6 core set variables (CSVs): 1. no of active joints; 2. no. of joints with pain or tenderness and limitation of motion; 3. ESR (mm/hr); 4. the Childhood Health Assessment Questionnaire (CHAQ); 5. Physician's Visual Analogue Scale (VAS); 6. Patient/Parent VAS. To fulfill ACR Pedi 75 criteria, 3/6 CSVs have to improve 75% and not more than 1/6 CSV worsen more than 30%. All direct and indirect costs are documented.

The first phase of the study is open-label clinical trial lasting for 54 weeks. In the second phase of the study the patients are followed up to 5 years, and the long-term outcome of early aggressive therapy is analyzed. Serum, urine, and saliva samples are collected at 3 and 5 years for translational research.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2013
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 15 Years

Eligibility

Inclusion Criteria:

• juvenile idiopathic arthritis

• arthritis lasting for at least 6 weeks but not more than 6 months

• polyarticular disease with at least 5 active joints with at least 3 joints with pain or tenderness and limitation of motion

• no previous treatment with DMARDs

Exclusion Criteria:

• systemic JIA

• any abnormality in the hematopoietic or lymphatic system

• any major concurrent medical condition

• inadequate psychosocial situation

• pregnancy

• a non-abstinent female with reproductive capacity without regular contraceptive use

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Infliximab plus methotrexate
IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.
• Combination of DMARDs
IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly, SSZ 40mg/kg up to 2000mg daily, HCQ 5mg/kg daily. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.
• Methotrexate alone
Oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.

Locations

Country	Name	City	State
Finland	Rheumatism Foundation Hospital	Heinola
Finland	Hospital for Children and Adolescents	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Central Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku

Sponsors (6)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Foundation for Paediatric Research, Finland, Paijat-Hame Hospital District, Päivikki and Sakari Sohlberg Foundation, Finland, Rheumatism Foundation Hospital, Scandinavian Rheumatology Research Foundation

Country where clinical trial is conducted

Finland, 

References & Publications (2)

Lahdenne P, Vähäsalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis. 2003 Mar;62(3):245-7. — View Citation

Tynjälä P, Vähäsalo P, Tarkiainen M, Kröger L, Aalto K, Malin M, Putto-Laurila A, Honkanen V, Lahdenne P. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinic — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ACR Pedi 75 response		54 weeks from baseline (0)	No
Secondary	clinically inactive disease		at 54 weeks	No
Secondary	time spent in inactive disease		0 to 54 weeks	No
Secondary	time spent in ACR Pedi 75		0 to 54 weeks	No
Secondary	Other ACR Pedi responses (30, 50, 70, 90, 100)		0 to 54 weeks	No
Secondary	drug survival		54 weeks	No
Secondary	occurrence of side-effects and adverse events		0 to 54 weeks	Yes
Secondary	cost-benefit ratio in each treatment arm		0 to 54 weeks	No

External Links

•   Registry of Clinical Trials in Helsinki University Central Hospital