Glucocorticoids Versus Placebo for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

NCT05674994 | Recruiting Phase 3 DMC

• 1 other identifier: EXAFIP2
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Efficacy of glucocorticoids compared to placebo on mortality

  This outcome corresponds to the all-cause mortality rate at day 30.

  Day 30

Secondary Outcomes (21)

• Time to death at Day 30

  Day 30

• Time to death at Day 90

  Day 90

• Death or transplantation at Day 90

  Day90

• Respiratory disease-specific mortality rate at Day 30

  Day 30

• Respiratory disease-specific mortality rate at Day 90

  Day 90

Study Arms (2)

MethylPrednisone/Prednisone

EXPERIMENTAL

* 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. The commercialized form for methylprednisolone injectable solution is not imposed and is taken from the stock of each pharmacy of the participating centers. * 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.

Drug: Methylprednisone/Prednisone

Placebo

PLACEBO COMPARATOR

* Day 1, 2 and 3: Intravenous Methylprednisolone-Placebo * From Day 4 to Day 30: Oral Prednisone-Placebo

Other: Placebo

Interventions

Placebo OTHER

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.

Placebo

Methylprednisone/Prednisone DRUG

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.

MethylPrednisone/Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ≥ 18 years of age
• IPF or IPF (likely) diagnosis defined on 2018 international recommendations
• \*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".
• 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.
• If no previous computed tomography is available, the qualifier "new" can be dropped from the third criterion.
• 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)
• Affiliation to the social security
• 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

You may not qualify if:

• Identified etiology for acute worsening (i.e.: infectious disease)
• Known hypersensitivity to glucocorticoids or to any component of the study treatment
• Patient requiring mechanical ventilation or already on mechanical ventilation
• 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.
• Active cancer
• Patient on a lung transplantation waiting list
• Treatment with glucocorticoids \> 1 mg/kg/d from more than 7 days in the last 15 days
• Patient participating to another interventional clinical trial
• Documented pregnancy or lactation
• Patient under tutorship or curatorship
• Patient deprived of liberty
• Patient under court protection

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Study Sites (29)

CHU ANgers

Angers, France

RECRUITING

CHU de Besancon

Besançon, France

RECRUITING

Hôpital Avicenne

Bobigny, France

NOT YET RECRUITING

CHU BOrdeaux

Bordeaux, France

RECRUITING

CHU Caen

Caen, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, France

NOT YET RECRUITING

CHIC

Créteil, France

RECRUITING

CHU de Dijon

Dijon, France

RECRUITING

CHU Grenoble

Grenoble, France

NOT YET RECRUITING

CHRU Lille

Lille, France

NOT YET RECRUITING

Hospices Civils de Lyon

Lyon, France

RECRUITING

Hôpital Nord

Marseille, France

RECRUITING

CHU de Montpellier

Montpellier, France

NOT YET RECRUITING

CHU Nancy

Nancy, France

RECRUITING

CHU de Nantes

Nantes, France

NOT YET RECRUITING

CHU Nice

Nice, France

NOT YET RECRUITING

Hôpital Paris Saint-Joseph

Paris, 75014, France

RECRUITING

Hôpital Bichat

Paris, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, France

RECRUITING

Hôpital FOCH

Paris, France

NOT YET RECRUITING

Hôpital Kremiln Bicetre

Paris, France

RECRUITING

Hôpital Saint-Louis

Paris, France

NOT YET RECRUITING

Hôpital Tenon

Paris, France

RECRUITING

CHU Reims

Reims, France

RECRUITING

CHU Rennes

Rennes, France

RECRUITING

CHU Rouen

Rouen, France

NOT YET RECRUITING

CHU Strasbourg

Strasbourg, France

NOT YET RECRUITING

CHU Toulouse

Toulouse, France

RECRUITING

CHU Tours

Tours, France

NOT YET RECRUITING

Related Publications (23)

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MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jean-Marc NACCACHE

  Fondation Hôpital Saint-Joseph

  STUDY DIRECTOR

Central Study Contacts

Jean-Marc NACCACHE, MD

CONTACT

144126747; jmnaccache@ghpsj.fr

Helene BEAUSSIER, PharmD, PhD

CONTACT

144127883; crc@ghpsj.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: January 9, 2023
• Study Start: October 26, 2023
• Primary Completion: March 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

FR (29)