Five-Year Actively Controlled Clinical Trial in New Onset Juvenile Systemic Lupus Erythematosus Nephritis
|Systemic Lupus Erythematosus Nephritis||Drug: cyclophosphamide-prednisone-azathioprine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||Five-Year Single-Blind, Phase III Effectiveness Randomised Actively Controlled Clinical Trial in New Onset Juvenile Systemic Lupus Erythematosus Nephritis: Oral Cyclophosphamide Versus High Dose Intravenous Cyclophosphamide Versus Intermediate Dose Intravenous Cyclophosphamide|
- Primary: 50% improvement in at least 2 core set variables with no more tha 1 of the remaining variables worsened by> 30%
- core set variables:
- physician’s global assessment of disease activity on a 10 cm visual analogue scale; global disease activity measure by the mean of the European Consensus Lupus Activity parent’s/patient’s global assessment of overall well-being on a 10 cm VAS;
- health-related quality of life assessment.
- Change over time in the individual components of the JSLE
- core set of variables; time to proteinuria disappearance; frequency of drop-out from
- suggested steroids use; frequency of drop-out for inefficacy of treatment.
|Study Start Date:||June 2006|
|Estimated Study Completion Date:||June 2007|
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 185 partners from 46 countries (110 in 21 EU States and 75 in 25 extra-EU States), with a randomised clinical trials (RCT) in juvenile systemic lupus erythematosus (JSLE): 5-year phase III single-blind, RCT in children with newly diagnosed, WHO class III, IV JSLE proliferative nephritis: PDN and oral cyclophosphamide (CYC) versus high dose intravenous (iv) CYC versus intermediate dose iv CYC, followed by maintenance with azathioprine. The JSLE RCT 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 JSLE 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 JSLE.
The proposed trials in in JSLE (oral cyclophosphamide [CYC] versus intermediate dose intravenous [iv] CYC versus high dose iv CYC) followed by maintenance therapy with azathioprine [AZA]), 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00336414
|Istituto Giannina Gaslini|
|Genoa, Italy, 16148|
|Principal Investigator:||Nicolino Ruperto, MD, MPH||Istituto Giannina Gaslini-PRINTO|