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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2009 by Helsinki University Central Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Foundation for Paediatric Research, Finland
Päivikki and Sakari Sohlberg Foundation, Finland
Rheumatism Foundation Hospital
Scandinavian Rheumatology Research Foundation
Paijat-Hame Hospital District
Information provided by:
Helsinki University Central Hospital
ClinicalTrials.gov Identifier:
NCT01015547
First received: November 17, 2009
Last updated: December 12, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: Infliximab plus methotrexate
Drug: Combination of DMARDs
Drug: Methotrexate alone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Helsinki University Central Hospital:

Primary Outcome Measures:
  • ACR Pedi 75 response [ Time Frame: 54 weeks from baseline (0) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • clinically inactive disease [ Time Frame: at 54 weeks ] [ Designated as safety issue: No ]
  • time spent in inactive disease [ Time Frame: 0 to 54 weeks ] [ Designated as safety issue: No ]
  • time spent in ACR Pedi 75 [ Time Frame: 0 to 54 weeks ] [ Designated as safety issue: No ]
  • Other ACR Pedi responses (30, 50, 70, 90, 100) [ Time Frame: 0 to 54 weeks ] [ Designated as safety issue: No ]
  • drug survival [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
  • occurrence of side-effects and adverse events [ Time Frame: 0 to 54 weeks ] [ Designated as safety issue: Yes ]
  • cost-benefit ratio in each treatment arm [ Time Frame: 0 to 54 weeks ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: May 2003
Estimated Study Completion Date: December 2012
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: MTX: Trexan or Methotrexate

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.

  Eligibility

Ages Eligible for Study:   4 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01015547

Locations
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, Finland
Sponsors and Collaborators
Helsinki University Central Hospital
Foundation for Paediatric Research, Finland
Päivikki and Sakari Sohlberg Foundation, Finland
Rheumatism Foundation Hospital
Scandinavian Rheumatology Research Foundation
Paijat-Hame Hospital District
Investigators
Study Director: Pekka Lahdenne, MD, PhD Hospital for Children and Adolescents in Helsinki University Central Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Pirjo Tynjälä, MD, PhD, Hospital for Children and Adolescents and Hospital District of Helsinki and Uusimaa
ClinicalTrials.gov Identifier: NCT01015547     History of Changes
Other Study ID Numbers: 211864, 318/E0/2002, 211864
Study First Received: November 17, 2009
Last Updated: December 12, 2009
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Helsinki University Central Hospital:
juvenile idiopathic arthritis
polyarthritis
combination therapy
biologic agents
TNF antagonists
infliximab

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Infliximab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on September 22, 2014