Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis (EXAFIP)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Idiopathic Pulmonary Fibrosis

Treatments: Drug: Corticosteroid (prednisolone); Drug: Placebo; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02460588

P 140908

2015-000492-27 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 2 patient groups, including a placebo group

Corticosteroid with placebo

Placebo Comparator group

Description:

Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below. All patients will receive non experimental medication with high dose of corticosteroid.

Treatment:

Drug: Placebo

Drug: Corticosteroid (prednisolone)

Corticosteroid associated with Cyclophosphamide

Experimental group

Description:

Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below. All patients will receive non experimental medication with high dose of corticosteroid. Intravenous Cyclophosphamide (CYC), 600 mg/m² (adapted to age and renal function, maximal dose of 1.2 g) at Day 0, Day 15, M1, M2

Treatment:

Drug: Corticosteroid (prednisolone)

Drug: Cyclophosphamide