Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease

• Status: Completed
• Trial end date: 2018-02-22
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Hôpital Claude-Huriez
• Treatments: Cyclophosphamide; Prednisone

Criteria

Inclusion Criteria:

• Age ≥ 18 years old

• Signed informed consent

• Patient with systemic sclerosis fulfilling the ACR -American college of rheumatology - (Masi et al. 1980) and/or Leroy and Medsger (LeRoy and Medsger 2001) diagnostics criteria with worsening ILD (interstitial lung disease) identified on a high resolution chest CT scan and by worsening of forced vital capacity (FVC) and/or total lung capacity (TLC) ≥10% and/or worsening of DLCO ≥ 15% as compared to values obtained within the 3 to 18 months preceding inclusion (for DLCO, in the absence of pulmonary arterial hypertension upon echocardiography)

• Smokers may be included (DLCO must be performed at least 72h after stopping tobacco intake).

• Patients with pulmonary hypertension (mean pulmonary arterial pressure <35 mmHg upon right heart catheterisation) secondary to hypoxia due to pulmonary fibrosis will also be included into the study.

• Physical examination prior to inclusion into the study (results must be given to the patient).

-: Contraception considered effective by the investigator (abstinence and / or oral contraception or mechanical) for women of childbearing age (negative pregnancy test at baseline)

• Affiliation with a mode of social security (profit or being entitled)

Exclusion Criteria:

• Prednisone prescribed a dose greater than 15 mg/d during the last 3 months.

• Scleroderma renal crisis or acute or critical limb ischemia within the last year preceding inclusion,

• Left ventricular ejection fraction below 40% evaluated by echocardiography.

• Out of proportion pulmonary hypertension (mean pulmonary artery pressure above 35 mmHg upon right heart catheterization).

• CYC treatment during the last 12 months.

• Allergy, hypersensitivity or documented adverse events or contra-indications to the drugs used in the study (cyclophosphamide, Uromitexan, corticosteroids, domperidone ...)

• Patients with a past history of cancer within four years before inclusion and/or a history of chemotherapy for cancer within four years before inclusion (in remission or without disease activity for more than four years). Inclusion is authorized for patients with a basal cell carcinoma in the last 5 years.

• Severe infection: sepsis, cellulitis, gangrene in the last three months

• Past history of cystitis related to cyclophosphamide treatment

• Association to another connective disease : systemic lupus erythematosus, syndrome of Gougerot-Sjögren with anti-SSA/SSB, mixed connective tissue disease

• Patient breastfeeding

• Failure to sign the informed consent or unable to consent

• Patient participating in another clinical trial

• Injection of Rituximab within 6 months preceding inclusion

• Methotrexate or Cellcept treatment at inclusion