Clinical trial NCT02460588: Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Official title: Cyclophosphamide Added to Corticosteroid in the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Placebo-controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-06-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: "Early" survival
timeFrame: 3 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 6 months and 12 montns
measure: Respiratory disease-specific mortality
timeFrame: 6 months
measure: Respiratory Morbidity
timeFrame: 6 months
measure: Chest HRCT features (HRCT images will be scored at 5 levels)
timeFrame: 6 months
measure: Prognosis factors of AE-IPF
timeFrame: 3 months
measure: Time to visit after clinical worsening
timeFrame: 3 months
measure: Laboratory evaluation (LDH, CRP) at AE diagnosis (composite)
timeFrame: 3 months
measure: Prognosis factors of AE-IPF
timeFrame: 3 months
measure: Prognosis factors of AE-IPF
timeFrame: 3 months
measure: Prognosis factors of AE-IPF
timeFrame: 3 months
measure: Time to dispense treatment of AE-IPF
timeFrame: 3 months
measure: Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy)
timeFrame: 6 months
measure: Number of Infectious disease
timeFrame: 6 months
measure: Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l)
timeFrame: 6 months
measure: Hypertension (Blood pressure > 160/100 mmHg)
timeFrame: 6 months
measure: Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE).
timeFrame: 6 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Tenon
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Marc NACCACHE, PH
role: PRINCIPAL_INVESTIGATOR
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