By including in this study patients with significant worsening of their lung volumes and / or their DLCO (carbon monoxide diffusing capacity) in the previous year, on the basis of an open retrospective study we recently conducted, we hope to demonstrate that a strategy combining prednisone and intravenous cyclophosphamide therapy is accompanied by an increase in the frequency stabilization / improvement of lung volumes and / or DLCO of patients at 12 months of 15% in the placebo and prednisone cyclophosphamide 50% in cyclophosphamide and prednisone.We also hope to demonstrate significant decrease in the number of patients excluded for failure in the CYC arm as compared to the placebo arm.
This is a randomized prospective multicenter study evaluating the efficacy against placebo of cyclophosphamide in combination with prednisone in the treatment of systemic sclerosis related interstitial lung disease. Patients will be allocated, after randomization into two groups receiving both corticosteroids: a group of patients receiving placebo of cyclophosphamide and a group of patients treated with cyclophosphamide. Cyclophosphamide will be administered IV at a dose of 0.7 g / m (maximum 1200 mg) every 4 weeks. In patients over 65 or if the creatinine clearance below 30 ml / min the dose should be reduced to 0.6 g / m². The duration of treatment with cyclophosphamide will be 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.
Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide
Cochin Hospital
Paris, France
Forced vital capacity
Forced vital capacity at 12 months
Time frame: at 12 months
Mortality
Time frame: at 12 months
Progression free survival
Progression free survival
Time frame: at 12 months
Carbon monoxide diffusing capacity (DLCO)
Time frame: at 12 months
Treatment failure
Failure of cyclophosphamide or placebo
Time frame: at 12 months
Walk test distance
Six minutes walk test distance, O2 desaturation and gradient between maximal and minimal SAO2 during the test
Time frame: at 12 months
Dyspnea
NYHA (Classification de la New York Heart Association), BDI (Beck Depression Inventory) and Borg index
Time frame: at 12 months
Health Assessment Questionnaire
Time frame: at 12 months
Quality of life
Saint-Georges; SF-36
Time frame: at 12 months
Chest CT (computed tomography) scan
CT (computed tomography) scan abnormalities
Time frame: at 12 months
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