Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

NCT ID: NCT01015547

Last Updated: 2015-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-05-31

Study Completion Date

2013-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Juvenile Idiopathic Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Infliximab plus Methotrexate

infliximab 3-5 mg/kg every 6 weeks, plus methotrexate 15 mg/m2 weekly given orally (dose escalation if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed.

Group Type EXPERIMENTAL

Infliximab plus methotrexate

Intervention Type DRUG

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

methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75), plus standard doses of sulfasalazine and hydroxychloroquine. no oral prednisolone. intra-articular steroids allowed.

Group Type EXPERIMENTAL

Combination of DMARDs

Intervention Type DRUG

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

Conventional drug therapy: methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed.

Group Type ACTIVE_COMPARATOR

Methotrexate alone

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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IFX: Remicade, MTX: Trexan or Methotrexate MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin MTX: Trexan or Methotrexate

Eligibility Criteria

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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
Minimum Eligible Age

4 Years

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Foundation for Paediatric Research, Finland

OTHER

Sponsor Role collaborator

Päivikki and Sakari Sohlberg Foundation, Finland

OTHER

Sponsor Role collaborator

Rheumatism Foundation Hospital

OTHER

Sponsor Role collaborator

Scandinavian Rheumatology Research Foundation

UNKNOWN

Sponsor Role collaborator

Paijat-Hame Hospital District

OTHER

Sponsor Role collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role lead

Responsible Party

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Pirjo Tynjala

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pekka Lahdenne, MD, PhD

Role: STUDY_DIRECTOR

Hospital for Children and Adolescents in Helsinki University Central Hospital

Locations

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Rheumatism Foundation Hospital

Heinola, , Finland

Site Status

Hospital for Children and Adolescents

Helsinki, , Finland

Site Status

Kuopio University Hospital

Kuopio, , Finland

Site Status

Oulu University Central Hospital

Oulu, , Finland

Site Status

Tampere University Hospital

Tampere, , Finland

Site Status

Turku University Hospital

Turku, , Finland

Site Status

Countries

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Finland

References

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Lahdenne P, Vahasalo 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. doi: 10.1136/ard.62.3.245.

Reference Type BACKGROUND
PMID: 12594111 (View on PubMed)

Tynjala P, Vahasalo P, Tarkiainen M, Kroger 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 clinical trial. Ann Rheum Dis. 2011 Sep;70(9):1605-12. doi: 10.1136/ard.2010.143347. Epub 2011 May 28.

Reference Type RESULT
PMID: 21623000 (View on PubMed)

Tarkiainen M, Tynjala P, Vahasalo P, Aalto K, Kroger L, Rebane K, Lahdenne P, Martikainen J. Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2022 Nov 16;20(1):97. doi: 10.1186/s12969-022-00748-w.

Reference Type DERIVED
PMID: 36384562 (View on PubMed)

Tarkiainen M, Tynjala P, Vahasalo P, Kroger L, Aalto K, Lahdenne P. Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis: results from randomized controlled trial. Pediatr Rheumatol Online J. 2019 Dec 16;17(1):80. doi: 10.1186/s12969-019-0370-1.

Reference Type DERIVED
PMID: 31842940 (View on PubMed)

Other Identifiers

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211864

Identifier Type: REGISTRY

Identifier Source: secondary_id

211864, 318/E0/2002

Identifier Type: -

Identifier Source: org_study_id

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