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Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis (EXAFIP)

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ClinicalTrials.gov Identifier: NCT02460588
Recruitment Status : Recruiting
First Posted : June 2, 2015
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Cyclophosphamide Drug: Placebo Drug: Corticosteroid (prednisolone) Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Cyclophosphamide Added to Corticosteroid in the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Placebo-controlled Randomized Trial
Actual Study Start Date : December 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019


Arm Intervention/treatment
Placebo Comparator: Corticosteroid with 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.

Drug: Placebo
Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below.
Other Name: Control group

Drug: Corticosteroid (prednisolone)
All patients will receive non experimental medication with high dose of corticosteroid.
Other Name: Both groups

Experimental: Corticosteroid associated with 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

Drug: Cyclophosphamide

Population is IPF patients with an AE who meet the inclusion and exclusion criteria defined below.

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


Drug: Corticosteroid (prednisolone)
All patients will receive non experimental medication with high dose of corticosteroid.
Other Name: Both groups




Primary Outcome Measures :
  1. "Early" survival [ Time Frame: 3 months ]
    All cause of mortality at 3 months


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 6 months and 12 montns ]
    Overall Survival at M6 and M12

  2. Respiratory disease-specific mortality [ Time Frame: 6 months ]
    Respiratory disease-specific mortality at M3 and M6

  3. Respiratory Morbidity [ Time Frame: 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% prednisolone

  4. Chest HRCT features (HRCT images will be scored at 5 levels) [ Time Frame: 6 months ]
    Chest HRCT features at M3 and M6 compared to inclusion

  5. Prognosis factors of AE-IPF [ Time Frame: 3 months ]
    PFTs results before AE-IPF

  6. Time to visit after clinical worsening [ Time Frame: 3 months ]
  7. Laboratory evaluation (LDH, CRP) at AE diagnosis (composite) [ Time Frame: 3 months ]
  8. Prognosis factors of AE-IPF [ Time Frame: 3 months ]
    PaO2 at AE diagnosis

  9. Prognosis factors of AE-IPF [ Time Frame: 3 months ]
    Chest HRCT features at AE diagnosis (HRCT images will be scored at 5 levels)

  10. Time to dispense treatment of AE-IPF [ Time Frame: 3 months ]
  11. Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy) [ Time Frame: 6 months ]
  12. Number of Infectious disease [ Time Frame: 6 months ]
  13. Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l) [ Time Frame: 6 months ]
  14. Hypertension (Blood pressure > 160/100 mmHg) [ Time Frame: 6 months ]
  15. Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE). [ Time Frame: 6 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460588


Contacts
Contact: Jean-Marc NACCACHE, PH 33 (0)1 56 01 61 96 jean-marc.naccache@tnn.aphp.fr
Contact: Hilario NUNES, PU-PH 33(0)3 48 95 51 21 hilario.nunes@avc.aphp.fr

Locations
France
Hôpital Tenon Recruiting
Paris, France
Contact: Jean-Marc NACCACHE    33 (0)1 56 01 61 96    jean-marc.naccache@tnn.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean-Marc NACCACHE, PH Assistance Publique - Hôpitaux de Paris

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02460588     History of Changes
Other Study ID Numbers: P 140908
2015-000492-27 ( EudraCT Number )
First Posted: June 2, 2015    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: December 2017

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Cyclophosphamide
Prednisolone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal