Clinical trial
Glucocorticoids Versus Placebo for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Randomized Controlled Trial
Name
EXAFIP2
Description
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with a poor prognosis, with a 3-month mortality rate of over 50%. To date, no treatment has been proven to be effective in AI-FPI. The interest of glucocorticoids is controversial and needs to be confirmed. This confirmation is mandatory to validate the improvement of the prognosis of EA-IPF under this treatment but also to search for unsuspected deleterious effects as it has been shown with immunosuppressants in stable idiopathic pulmonary fibrosis.
Trial arms
Trial start
2023-10-26
Estimated PCD
2025-10-25
Trial end
2026-12-31
Status
Recruiting
Phase
Early phase I
Treatment
Methylprednisone/Prednisone
Patients will be enrolled during their hospitalization in pneumology department, as part of current practice, within 7 days of the screening visit. The investigator will perform randomization by connecting to the eCRF, randomization be stratified for the severity of IPF and the treatment with antifibrotic therapy (Nintedanib or Pirfenidone) (yes/no).
If patient is randomized in Glucocorticoids Group:
* Day 1, 2 and 3: Intravenous Methylprednisolone 10 mg/kg/d (without exceeding 1000 mg/d). Vials of injectable solution of methylprednisolone® are diluted in 100 ml of NaCl 0.9% or G5%. Perfusion duration is between 20 to 30 minutes.
* From day 4 to Day 30: Oral Prednisone slow tappering
* 1 mg/kg/d for 7 days
* 0.5 mg/kg/d for 7 days
* 0.25 mg/kg/d for 7 days,
* 10 mg/d until Day 30. For 10mg/kg, 1 mg/kg, 0.5 mg/kg, 0.25 mg/kg; rounding to 5 decimal lower if decimal ≤ 7 and the top ten if decimal ≥ 8.
Arms:
MethylPrednisone/Prednisone
Placebo
Patients will be enrolled during their hospitalization in pneumology department, as part of current practice, within 7 days of the screening visit. The investigator will perform randomization by connecting to the eCRF, randomization be stratified for the severity of IPF and the treatment with antifibrotic therapy (Nintedanib or Pirfenidone) (yes/no).
If patient is randomized in Placebo Group:
Day 1, 2 and 3: Intravenous Methylprednisolone-Placebo From Day 4 to Day 30: Oral Prednisone-Placebo The Methylprednisolone-Placebo corresponds to 100 ml of NaCl 0.9 % or G5%. Perfusion duration is between 20 to 30 minutes.
For the Prednisone-Placebo, the placebo was an oral solution formulated with a bittering agent (pharmaceutical excipient). Specifically, in place of prednisone, sucrose octaacetate (defined as a GRAS-'Generally Recognized as Safe' excipient by the EMA) was used at 5 mg/mL.
Arms:
Placebo
Size
110
Primary endpoint
Efficacy of glucocorticoids compared to placebo on mortality
Day 30
Eligibility criteria
Inclusion Criteria:
1. Patient is ≥ 18 years of age
2. IPF or IPF (likely) diagnosis defined on 2018 international recommendations
3. Definite or suspected Acute Exacerbation defined by the international working group criteria after exclusion of alternative diagnoses of acute worsening
\*The criteria of IPF-AE are as follows:
* Previous or concurrent diagnosis of IPF (a)
* Acute worsening or development of dyspnea typically \< 1-month duration
* Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern (b)
* Deterioration not fully explained by cardiac failure or fluid overload Patients who fail to meet all 4 criteria due to missing computed tomography should be considered as having "suspected Acute Exacerbation".
1. If the diagnosis of IPF is not previously established, this criterion can be met by the presence of radiologic and/or histopathologic changes consistent with usual interstitial pneumonia pattern on the current evaluation.
2. If no previous computed tomography is available, the qualifier "new" can be dropped from the third criterion.
4. For women of childbearing age: efficient contraception for the duration of the study\*
\*Effective contraception is defined as any contraceptive method that is used consistently and appropriately and has a low failure rate (i.e., less than 1% per year)
5. Affiliation to the social security
6. Patient able to understand and sign a written informed consent form or in case of incapacity of the patient to a relative whom understand and sign a written informed consent form
Exclusion Criteria:
1. Identified etiology for acute worsening (i.e.: infectious disease)
2. Known hypersensitivity to glucocorticoids or to any component of the study treatment
3. Patient requiring mechanical ventilation or already on mechanical ventilation
4. Active bacterial, viral, fungal or parasitic infection. On swab collected, only positive for SARS-CoV-2, Influenzae A, Influenzae B and Respiratory Syncytial Virus (RSV) result, are considered active viral infection. The others viruses (i.e. Rhinovirus, Adenovirus...) are not considered to be responsible of pneumonia.
5. Active cancer
6. Patient on a lung transplantation waiting list
7. Treatment with glucocorticoids \> 1 mg/kg/d from more than 7 days in the last 15 days
8. Patient participating to another interventional clinical trial
9. Documented pregnancy or lactation
10. Patient under tutorship or curatorship
11. Patient deprived of liberty
12. Patient under court protection
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 110, 'type': 'ESTIMATED'}}
Updated at
2023-12-15
1 organization
Organization
Fondation Hôpital Saint-Joseph