EXAFIP: Cyclophosphamide for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Completed
CT.gov ID
NCT02460588
Collaborator
(none)
120
1
2
43
2.8

Study Details

Study Description

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
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 Design

Study Type:
Interventional
Actual 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 :
Dec 1, 2015
Actual Primary Completion Date :
Jan 1, 2019
Actual Study Completion Date :
Jul 1, 2019

Arms and Interventions

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 Names:
  • Control group
  • Drug: Corticosteroid (prednisolone)
    All patients will receive non experimental medication with high dose of corticosteroid.
    Other Names:
  • 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 Names:
  • Both groups
  • Outcome Measures

    Primary Outcome Measures

    1. "Early" survival [3 months]

      All cause of mortality at 3 months

    Secondary Outcome Measures

    1. Overall Survival [6 months and 12 montns]

      Overall Survival at M6 and M12

    2. Respiratory disease-specific mortality [6 months]

      Respiratory disease-specific mortality at M3 and M6

    3. 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% prednisolone

    4. Chest HRCT features (HRCT images will be scored at 5 levels) [6 months]

      Chest HRCT features at M3 and M6 compared to inclusion

    5. Prognosis factors of AE-IPF [3 months]

      PFTs results before AE-IPF

    6. Time to visit after clinical worsening [3 months]

    7. Laboratory evaluation (LDH, CRP) at AE diagnosis (composite) [3 months]

    8. Prognosis factors of AE-IPF [3 months]

      PaO2 at AE diagnosis

    9. Prognosis factors of AE-IPF [3 months]

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

    10. Prognosis factors of AE-IPF [3 months]

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

    11. Time to dispense treatment of AE-IPF [3 months]

    12. Hemorrhagic cystitis (occurence of hematuria on urine dipstick and pelvic pain and/or dysuria should lead to cystoscopy) [6 months]

    13. Number of Infectious disease [6 months]

    14. Diabetes mellitus (capillary blood glucose monitoring and fasting plasma glucose > 1.26 g/l) [6 months]

    15. Hypertension (Blood pressure > 160/100 mmHg) [6 months]

    16. Clinical laboratory evaluation (blood count, serum creatinin measurement composite) according to Common Terminology Criteria for Adverse Event (CTCAE). [6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hôpital Tenon Paris France

    Sponsors and Collaborators

    • Assistance Publique - Hôpitaux de Paris

    Investigators

    • Principal Investigator: Jean-Marc NACCACHE, PH, Assistance Publique - Hôpitaux de Paris

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Assistance Publique - Hôpitaux de Paris
    ClinicalTrials.gov Identifier:
    NCT02460588
    Other Study ID Numbers:
    • P 140908
    • 2015-000492-27
    First Posted:
    Jun 2, 2015
    Last Update Posted:
    Jun 30, 2022
    Last Verified:
    Jun 1, 2022

    Study Results

    No Results Posted as of Jun 30, 2022