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.

Idiopathic pulmonary fibrosis (IPF) is the most frequent idiopathic interstitial lung disease (ILD) in adults. Its prognosis is poor with a median survival time ranging from 2 to 3 years. Acute exacerbation of IPF (IPF-AE) is defined as acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormalities. Recently, diagnosis criteria were defined now allowing standardized diagnosis of IPF-AE and thus its study. IPF-AE is a major event of the disease having a 5 to 10% annual incidence. In-hospital mortality after IPF-AE exceeds 50% and current evidence suggests that up to 46% of deaths in IPF patients are associated with IPF-AE.

For the time being, no treatment has been proved to be effective in IPF-AE. While the clinical practice guideline suggests treatment with steroids, this recommendation is based only on expert opinion (low level evidence). Retrospective studies suggested the efficacy of thrombomodulin, cyclophosphamide or of therapeutic strategy including plasma exchange, rituximab and intravenous immunoglobulins. A recent Japanese randomized trial failed to show the efficacy of thrombomodulin alfa. Investigators performed a randomized trial assessing the role of cyclophosphamide on top of pulse steroid (EXAFIP-NCT02460588) and showed that cyclophosphamide did not reduce the 3-month mortality. A study assessing the effect of therapeutic plasma exchange, rituximab and intravenous immunoglobulins for severe form of IPF-AE patients admitted to Intensive Care Unit (ICU) is still ongoing (NCT03286556). Presently, the clinical benefit of corticosteroids is questioned. Indeed, 2 retrospective series reported an absence of outcome improvement by corticosteroids among IPF-AE patients and even suggested a potential detrimental outcome.

It is therefore necessary to set-up a placebo-controlled randomized trial: investigator's goal is to test the hypothesis that a corticosteroid treatment is highly efficient in IPF-AE, compared to placebo.

This underlines that, as no good evidence is available to support the use of glucocorticoids in IPF-AE, randomized controlled trials are also needed to address their efficacy and safety in this indication.

The choices of glucocorticoids' dosage, primary objective (mortality) and primary assessment criteria (all cause mortality rate at Day 30) are driven by investigator's previous study, EXAFIP. In this study, glucocorticoids dosage was as follow: intravenous methylprednisolone, 10 mg/kg/d (without exceeding 1000 mg/d), 3 days in a row shift to prednisone at 1 mg/kg/d for 1 week, and 0.75 mg/kg/d for 1 week, then 0.5 mg/kg/d for 1 week, and 0.25 mg/kg/d for 1 week, and 10 mg/d if weight > 65 kg; 7.5 mg if weight ≤ 65 kg until M6. The 1-month mortality of patient under this high dose of glucocorticoids was 20%.

In view of the poor prognosis of IPF-AE, it seems also important to evaluate the effect of treatment on overall mortality at Day 90.

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