Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA)

October 13, 2015 updated by: Pirjo Tynjala, Helsinki University Central Hospital

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Heinola, Finland
        • Rheumatism Foundation Hospital
      • Helsinki, Finland
        • Hospital for Children and Adolescents
      • Kuopio, Finland
        • Kuopio University Hospital
      • Oulu, Finland
        • Oulu University Central Hospital
      • Tampere, Finland
        • Tampere University hospital
      • Turku, Finland
        • Turku University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.
Other Names:
  • IFX: Remicade, MTX: Trexan or Methotrexate
Experimental: 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.
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.
Other Names:
  • MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin
Active Comparator: 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.
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.
Other Names:
  • MTX: Trexan or Methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
ACR Pedi 75 response
Time Frame: 54 weeks from baseline (0)
54 weeks from baseline (0)

Secondary Outcome Measures

Outcome Measure
Time Frame
clinically inactive disease
Time Frame: at 54 weeks
at 54 weeks
time spent in inactive disease
Time Frame: 0 to 54 weeks
0 to 54 weeks
time spent in ACR Pedi 75
Time Frame: 0 to 54 weeks
0 to 54 weeks
Other ACR Pedi responses (30, 50, 70, 90, 100)
Time Frame: 0 to 54 weeks
0 to 54 weeks
drug survival
Time Frame: 54 weeks
54 weeks
occurrence of side-effects and adverse events
Time Frame: 0 to 54 weeks
0 to 54 weeks
cost-benefit ratio in each treatment arm
Time Frame: 0 to 54 weeks
0 to 54 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Helsinki University Central Hospital

Collaborators

Foundation for Paediatric Research, Finland
Päivikki and Sakari Sohlberg Foundation, Finland
Paijat-Hame Hospital District
Rheumatism Foundation Hospital
Scandinavian Rheumatology Research Foundation

Investigators

  • Study Director: Pekka Lahdenne, MD, PhD, Hospital for Children and Adolescents in Helsinki University Central Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

November 17, 2009

First Submitted That Met QC Criteria

November 17, 2009

First Posted (Estimate)

November 18, 2009

Study Record Updates

Last Update Posted (Estimate)

October 15, 2015

Last Update Submitted That Met QC Criteria

October 13, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 211864, 318/E0/2002
  • 211864 (Registry Identifier: www.hus.fi)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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