Clinical trial NCT00323960
Conditions: Juvenile Dermatomyositis
Keywords: Juvenile dermatomyositis randomised actively controlled clinical trial prednisone cyclosporine methotrexate effectiveness
Sponsor: Istituto Giannina Gaslini
Start date: 2006-05-31; Completion date: 2015-11-29
Enrollment: 139 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a 5-year project, involving 185 partners from 46 countries ((110 in 21 European Union (EU) States and 75 in 25 extra-EU States)), with a randomised clinical trials (RCT) in juvenile dermatomyositis (JDM): 5-year phase III single-blind, RCT in children with newly diagnosed JDM: prednisone (PDN) versus PDN plus methotrexate (MTX) versus PDN plus Cyclosporine A. The trial is aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity

Detailed description:
Scientific objectives: The proposed project is aimed to improve treatment approaches for rare, severe and disabling paediatric rheumatic diseases (PRD). This goal will be achieved by the Paediatric Rheumatology International Trials Organisation (PRINTO) an international network whose main function is to provide a scientific base for current PRD treatments for which no evidence based data exist in the literature, and for drugs for which there is no support from industries.

This is a 5-year project, involving 46 countries (110 in 21 EU States and 75 in 25 extra-EU States), with a randomised clinical trials (RCT) in juvenile dermatomyositis (JDM): 5-year phase III single-blind, RCT in children with newly diagnosed JDM: prednisone (PDN) versus PDN plus methotrexate (MTX) versus PDN plus Cyclosporine A (CsA). The trial is aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity. The retention on treatment will be used as main measure of effectiveness.

Methodology: The present protocol is the natural follow up of previous work conducted by PRINTO. In particular the RCT foreseen in this protocol is modelled after the successful completion of an early phase trial with MTX in juvenile idiopathic arthritis, and will use validated JDM outcome measures for the evaluation of response to therapy.

It is the basic premise of this protocol that, without i) the involvement of the international paediatric rheumatology community, ii) the innovative type of mechanism described herein, these studies would never be conducted.

Objectives. The goals of the current protocol is therefore the natural follow-up of the objectives achieved with the previous grants and, in particular, of projects designed to discern new models for the successful conduct of clinical trials in children with rare diseases, and to develop standardized and validated measures for the evaluation of response to therapy in JDM.

The proposed trial in JDM (prednisone \[PDN\] versus PDN plus methotrexate \[MTX\] versus PDN plus cyclosporine \[CsA\]), should serve as a model for the successful running of early phase clinical trials for severe and disabling rare diseases of childhood.

The ultimate aim of these trials is to provide evidence-based information about the clinical utility of drugs in the management of rare paediatric conditions.

Arms: arm 1: MPDN= methylprednisolone pulse PDN= prednisone or equivalent CSA= cyclosporine A arm 2: MPDN= methylprednisolone pulse PDN= prednisone or equivalent MTX= methotrexate arm 3: MPDN= methylprednisolone PDN= prednisone or equivalent
Interventions: intervention 1: 3 MPDN pulse + PDN intervention 2: 3 MPDN pulse + PDN + CSA intervention 3: 3 MPDN pulse + PDN + MTX
Intervention descriptions: intervention 1: 3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years. intervention 2: 3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years; Cyclosporine 5 mg/Kg/day in 2 oral doses intervention 3: 3 methylprednisolone pulses followed (30 mg/kg/pulse max 1 gram) followed by prednisone 2 mg/Kg/day to be tapered to 0.2 mg/kg/day in 6 months and then discontinued in 2 years; Methotrexate 15-20 mg/m2 once per week. Patients treated with MTX will receive concomitant folic or folinic acid according to the attending physician decision.

Protocol documents:
Prot_000.pdf: 
COVER PAGE 
Official title: “FIVE-YEAR SINGLE-BLIND, PHASE III EFFECTIVENESS RANDOMISED 
ACTIVELY CONTROLLED CLINICAL TRIAL IN NEW ONSET JUVENILE 
DERMATOMYOSITIS: PREDNISONE VERSUS PREDNISONE PLUS CYCLOSPORINE A 
VERSUS PREDNISONE PLUS METHOTREXATE” 
NCT number: NCT00323960 
Document date: 23rd February 2007