Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Assistance Publique - Hôpitaux de Paris120 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

120

Conditions

Idiopathic Pulmonary Fibrosis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

"Early" survival

All cause of mortality at 3 months

Time frame: 3 months

Secondary Outcomes

Overall Survival

Overall Survival at M6 and M12

Time frame: 6 months and 12 montns

Respiratory disease-specific mortality

Respiratory disease-specific mortality at M3 and M6

Time frame: 6 months

Respiratory Morbidity

\\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% prednisolone

Time frame: 6 months

Chest HRCT features (HRCT images will be scored at 5 levels)

Chest HRCT features at M3 and M6 compared to inclusion

Time frame: 6 months

Prognosis factors of AE-IPF

PFTs results before AE-IPF

Time frame: 3 months

Time to visit after clinical worsening

Time frame: 3 months

Laboratory evaluation (LDH, CRP) at AE diagnosis (composite)

Time frame: 3 months

Prognosis factors of AE-IPF

PaO2 at AE diagnosis

Time frame: 3 months

Prognosis factors of AE-IPF

Chest HRCT features at AE diagnosis compared to HRCT before AE-IPF (if available)

Time frame: 3 months

Prognosis factors of AE-IPF

Chest HRCT classification before AE-IPF (definite UIP, probable UIP, indeterminate), if available

Time frame: 3 months

Time to dispense treatment of AE-IPF

Time frame: 3 months

Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy)

Time frame: 6 months

Number of Infectious disease

Time frame: 6 months

Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l)

Time frame: 6 months

Hypertension (Blood pressure > 160/100 mmHg)

Time frame: 6 months

Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE).

Time frame: 6 months

Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes