Juvenile Idiopathic ArthritisPhase 3ACUTE-JIANCT01015547
Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis
A Phase 3 study testing Infliximab plus methotrexate, Combination of DMARDs and Methotrexate alone in people with Juvenile Idiopathic Arthritis, run by Helsinki University Central Hospital at 6 sites in Finland.
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. Read more about this study
- Who is it for?
- Ages 4 to 15 years
- Conditions the study is for
- Juvenile Idiopathic Arthritis
- What is being tested?
- Infliximab plus methotrexate, Combination of DMARDs and Methotrexate alone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 6 sitesFinland
- Study dates
- May 2003to Dec 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Finland6 sites
Rheumatism Foundation Hospital
Heinola
Hospital for Children and Adolescents
Helsinki
Kuopio University Hospital
Kuopio
Oulu University Central Hospital
Oulu
Tampere University Hospital
Tampere
Turku University Hospital
Turku
About this study
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.
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.
Read the 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.
- Conditions
- Juvenile Idiopathic Arthritis
- Being tested
- Infliximab plus methotrexate, Combination of DMARDs, Methotrexate alone
- Keywords
- juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab
- Medical subject headings
- Arthritis, Juvenile, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infliximab plus methotrexateDrug
Also called IFX: Remicade, MTX: Trexan or 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 DMARDsDrug
Also called MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin
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 aloneDrug
Also called MTX: Trexan or Methotrexate
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.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab plus Methotrexate | Experimental | 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. Receives: Drug: Infliximab plus methotrexate |
| Combination of DMARDs | Experimental | 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. Receives: Drug: Combination of DMARDs |
| Methotrexate alone | Active comparator | 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. Receives: Drug: Methotrexate alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
ACR Pedi 75 response
Measured: 54 weeks from baseline (0)
Secondary outcomes (7)
clinically inactive disease
Measured: at 54 weeks
time spent in inactive disease
Measured: 0 to 54 weeks
time spent in ACR Pedi 75
Measured: 0 to 54 weeks
Other ACR Pedi responses (30, 50, 70, 90, 100)
Measured: 0 to 54 weeks
drug survival
Measured: 54 weeks
occurrence of side-effects and adverse events
Measured: 0 to 54 weeks
cost-benefit ratio in each treatment arm
Measured: 0 to 54 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2009 (estimated)
- Study startMay 2003
- Primary completionNov 2007
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Paediatric Research, Finland, Päivikki and Sakari Sohlberg Foundation, Finland, Rheumatism Foundation Hospital, Scandinavian Rheumatology Research Foundation, Paijat-Hame Hospital District
- Responsible party
- Principal investigator, Pirjo Tynjala, Helsinki University Central Hospital
- Investigators
- Pekka Lahdenne, MD, PhD, Study director, Hospital for Children and Adolescents in Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01015547
- Sponsor's protocol ID
- 211864, 318/E0/2002
- Other IDs
- 211864
- Acronym
- ACUTE-JIA
- Status last verified
- Oct 2015
- First submitted
- 17 Nov 2009
- Last updated
- 15 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 12594111Tynjala 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.
PubMed 21623000Tarkiainen 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.
PubMed 36384562Tarkiainen 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.
PubMed 31842940
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01015547
- Acronym / sponsor ID
- ACUTE-JIA / 211864, 318/E0/2002
- Conditions
- Juvenile Idiopathic Arthritis
- Keywords
- juvenile idiopathic arthritis, polyarthritis, combination therapy, biologic agents, TNF antagonists, infliximab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Foundation for Paediatric Research, Finland, Päivikki and Sakari Sohlberg Foundation, Finland, Rheumatism Foundation Hospital, Scandinavian Rheumatology Research Foundation, Paijat-Hame Hospital District
- Study start
- May 2003
- Primary completion
- Nov 2007 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 18 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Infliximab plus Methotrexate | Experimental | Drug: Infliximab plus methotrexateinfliximab 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. |
| Combination of DMARDs | Experimental | Drug: Combination of DMARDsmethotrexate 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. |
| Methotrexate alone | Active comparator | Drug: Methotrexate aloneConventional 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. |
Who may qualify
- Ages
- 4 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- systemic JIA
- any abnormality in the hematopoietic or lymphatic system
- any major concurrent medical condition
- inadequate psychosocial situation
- pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Infliximab plus methotrexateAlso: IFX: Remicade, MTX: Trexan or MethotrexateIFX 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. | Drug | Infliximab plus Methotrexate |
| Combination of DMARDsAlso: MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: OxiklorinIFX 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. | Drug | Combination of DMARDs |
| Methotrexate aloneAlso: MTX: Trexan or MethotrexateOral 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. | Drug | Methotrexate alone |
Primary outcome
ACR Pedi 75 response
Time frame: 54 weeks from baseline (0)
7 secondary outcomes
clinically inactive disease
Time frame: at 54 weeks
time spent in inactive disease
Time frame: 0 to 54 weeks
time spent in ACR Pedi 75
Time frame: 0 to 54 weeks
Other ACR Pedi responses (30, 50, 70, 90, 100)
Time frame: 0 to 54 weeks
drug survival
Time frame: 54 weeks
occurrence of side-effects and adverse events
Time frame: 0 to 54 weeks
cost-benefit ratio in each treatment arm
Time frame: 0 to 54 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2015.
- Background: PubMed 12594111Lahdenne 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 publication: PubMed 21623000Tynjala 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.
- Derived from this study: PubMed 36384562Tarkiainen 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.
- Derived from this study: PubMed 31842940Tarkiainen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pekka Lahdenne, MD, PhD study director
Hospital for Children and Adolescents in Helsinki University Central Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Infliximab plus methotrexate, Combination of DMARDs and Methotrexate alone in people with Juvenile Idiopathic Arthritis, run by Helsinki University Central Hospital at 6 sites in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACR Pedi 75 response (time frame: 54 weeks from baseline (0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01015547, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2015.