Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis
- Conditions
- Idiopathic Pulmonary Fibrosis
- Interventions
- Registration Number
- NCT02460588
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 120
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Corticosteroid with placebo Corticosteroid (prednisolone) 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. Corticosteroid with placebo Placebo 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. Corticosteroid associated with Cyclophosphamide Corticosteroid (prednisolone) 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 Corticosteroid associated with Cyclophosphamide Cyclophosphamide 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
- Primary Outcome Measures
Name Time Method "Early" survival 3 months All cause of mortality at 3 months
- Secondary Outcome Measures
Name Time Method Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l) 6 months Respiratory disease-specific mortality 6 months Respiratory disease-specific mortality at M3 and M6
Prognosis factors of AE-IPF 3 months Chest HRCT classification before AE-IPF (definite UIP, probable UIP, indeterminate), if available
Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE). 6 months Overall Survival 6 months and 12 montns Overall Survival at M6 and M12
Respiratory Morbidity 6 months \\Worsening dyspnea (0-100-mm visual analogue (VAS) scale anchored with 0 ''no breathlessness'' and 10 or 100 ''worst imaginable breathlessness". Worsening is defined an absolute decrease of 10 mm)
* Or Increase need of supplemental oxygen of more than 3l/min to obtained a SaO2 \> 90% or decrease of PaO2 of more than 10 mmHg with the same rate of flow supplemental oxygen
* Or Decrease FVC of more than 10% of predicted value
* Or Decrease diffuse capacity for carbon monoxide (DLCO) of more than 15% prednisoloneTime to visit after clinical worsening 3 months Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy) 6 months Chest HRCT features (HRCT images will be scored at 5 levels) 6 months Chest HRCT features at M3 and M6 compared to inclusion
Time to dispense treatment of AE-IPF 3 months Hypertension (Blood pressure > 160/100 mmHg) 6 months Laboratory evaluation (LDH, CRP) at AE diagnosis (composite) 3 months Number of Infectious disease 6 months
Trial Locations
- Locations (1)
Hôpital Tenon
🇫🇷Paris, France