Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Cyclophosphamide Added to Corticosteroid in the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Placebo-controlled Randomized Trial

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a major event of IPF with an annual incidence between 5 and 10% and is responsible for the death of one third of IPF patients. When AE-IPF occurs, it is associated with poor survival with an overall mortality at 3 months upper of 50%. To date, no treatment has been proved to be effective in AE-IPF but the efficacy of cyclophosphamide (CYC) on survival has been suggested, mainly by retrospective series and needs to be confirmed. This confirmation is mandatory to improve prognosis of AE-IPF but also to avoid unsuspected deleterious effect as it as been shown with immunosuppressor in stable IPF.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a major event of IPF with an annual incidence between 5 and 10% and is responsible for the death of one third of IPF patients. When AE-IPF occurs, it is associated with poor survival with an overall mortality at 3 months upper of 50%. To date, no treatment has been proved to be effective in AE-IPF but the efficacy of CYC on survival has been suggested, mainly by retrospective series and needs to be confirmed. This confirmation is mandatory to improve prognosis of AE-IPF but also to avoid unsuspected deleterious effect as it as been shown with immunosuppressor in stable IPF.

Inclusion Criteria :

• ≥18 years of age
• Definite or probable IPF diagnosis defined on 2011 international recommendations
• Definite or suspicion of AE defined by IPFnet criteria after exclusion of alternative diagnosis of acute worsening.
• Efficient contraceptive method within 1 month for women and 3 months for men after the last dose of treatment
• Affiliation to the social security
• Able to understand and sign a written informed consent form

Exclusion Criteria:

• Identified etiology for acute worsening (i.e. infectious disease)
• Known hypersensitivity or contra-indication to CYC or to any component of the study treatment
• Patient on mechanical ventilation
• Active bacterial, viral, fungal or parasitic infection
• Active cancer
• Patient on a lung transplantation waiting list
• Treatment with CYC in the last 12 months
• Patient participating to another clinical trial
• Pregnancy or lactation