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

Primary Purpose

Juvenile Idiopathic Arthritis

Status
Completed
Phase
Phase 3
Locations
Finland
Study Type
Interventional
Intervention
Infliximab plus methotrexate
Combination of DMARDs
Methotrexate alone
Sponsored by
Helsinki University Central Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Juvenile Idiopathic Arthritis focused on measuring juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab

Eligibility Criteria

4 Years - 15 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rheumatism Foundation Hospital
  • Hospital for Children and Adolescents
  • Kuopio University Hospital
  • Oulu University Central Hospital
  • Tampere University Hospital
  • Turku University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Infliximab plus Methotrexate

Combination of DMARDs

Methotrexate alone

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

ACR Pedi 75 response

Secondary Outcome Measures

clinically inactive disease
time spent in inactive disease
time spent in ACR Pedi 75
Other ACR Pedi responses (30, 50, 70, 90, 100)
drug survival
occurrence of side-effects and adverse events
cost-benefit ratio in each treatment arm

Full Information

First Posted
November 17, 2009
Last Updated
October 13, 2015
Sponsor
Helsinki University Central Hospital
Collaborators
Foundation for Paediatric Research, Finland, Päivikki and Sakari Sohlberg Foundation, Finland, Rheumatism Foundation Hospital, Scandinavian Rheumatology Research Foundation, Paijat-Hame Hospital District
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1. Study Identification

Unique Protocol Identification Number
NCT01015547
Brief Title
Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Helsinki University Central Hospital
Collaborators
Foundation for Paediatric Research, Finland, Päivikki and Sakari Sohlberg Foundation, Finland, Rheumatism Foundation Hospital, Scandinavian Rheumatology Research Foundation, Paijat-Hame Hospital District

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis
Keywords
juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Infliximab plus Methotrexate
Arm Type
Experimental
Arm Description
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.
Arm Title
Combination of DMARDs
Arm Type
Experimental
Arm Description
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.
Arm Title
Methotrexate alone
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Infliximab plus methotrexate
Other Intervention Name(s)
IFX: Remicade, MTX: Trexan or Methotrexate
Intervention Description
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
Intervention Name(s)
Combination of DMARDs
Other Intervention Name(s)
MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin
Intervention Description
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
Intervention Name(s)
Methotrexate alone
Other Intervention Name(s)
MTX: Trexan or Methotrexate
Intervention Description
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.
Primary Outcome Measure Information:
Title
ACR Pedi 75 response
Time Frame
54 weeks from baseline (0)
Secondary Outcome Measure Information:
Title
clinically inactive disease
Time Frame
at 54 weeks
Title
time spent in inactive disease
Time Frame
0 to 54 weeks
Title
time spent in ACR Pedi 75
Time Frame
0 to 54 weeks
Title
Other ACR Pedi responses (30, 50, 70, 90, 100)
Time Frame
0 to 54 weeks
Title
drug survival
Time Frame
54 weeks
Title
occurrence of side-effects and adverse events
Time Frame
0 to 54 weeks
Title
cost-benefit ratio in each treatment arm
Time Frame
0 to 54 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pekka Lahdenne, MD, PhD
Organizational Affiliation
Hospital for Children and Adolescents in Helsinki University Central Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Rheumatism Foundation Hospital
City
Heinola
Country
Finland
Facility Name
Hospital for Children and Adolescents
City
Helsinki
Country
Finland
Facility Name
Kuopio University Hospital
City
Kuopio
Country
Finland
Facility Name
Oulu University Central Hospital
City
Oulu
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
Country
Finland
Facility Name
Turku University Hospital
City
Turku
Country
Finland

12. IPD Sharing Statement

Citations:
PubMed Identifier
12594111
Citation
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.
Results Reference
background
PubMed Identifier
21623000
Citation
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.
Results Reference
result
PubMed Identifier
36384562
Citation
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.
Results Reference
derived
PubMed Identifier
31842940
Citation
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.
Results Reference
derived

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Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis

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