Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT05674994 En recrutement IDF

Titre

Glucocorticoids Versus Placebo for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Randomized Controlled Trial (EXAFIP2)

Type

Interventional

Pathologie

Fibrose
Fibrose pulmonaire
Fibrose pulmonaire idiopathique

Phase

Phase 3

Promoteur

Fondation Hôpital Saint-Joseph (Voir sur ClinicalTrials)

Date de début

octobre 2023

Date de fin

décembre 2026

Dernière mise à jour

29 juin 2024

Résumé

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.

Détail

Voir le détail 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. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
AP-HP - Hôpital Avicenne	ALEXANDRE CHABROL	En recrutement IDF	30/12/2024 08:02:34	Contacter
CHI DE CRETEIL	Quentin GIBIOT	Active, sans recrutement	29/03/2024 01:30:41	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Bichat	Bruno CRESTANI, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Europeen Georges Pompidou	Jean PASTRE, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Tenon	Jacques CADRANEL, MD	En recrutement IDF		Contact (sur clinicalTrials)
GH PARIS SITE SAINT JOSEPH	Jean-Marc NACCACHE, MD	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CHIC - Créteil - France	Quentin GIBIOT, MD	En recrutement		Contact (sur clinicalTrials)
CHRU Lille - Lille - France	Victor VALENTIN, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU ANgers - Angers - France	Frederic GAGNADOUX	En recrutement		Contact (sur clinicalTrials)
CHU BOrdeaux - Bordeaux - France	Elodie BLANCHARD, MD	En recrutement		Contact (sur clinicalTrials)
CHU Caen - Caen - France	Emmanuel BERGOT, MD	En recrutement		Contact (sur clinicalTrials)
CHU Clermont-Ferrand - Clermont-Ferrand - France	Camille ROLLAND DEBORD, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU de Besancon - Besançon - France	Mathilde DUPREZ, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Dijon - Dijon - France	Philippe BONNIAUD, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Montpellier - Montpellier - France	Arnaud BOURDIN, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU de Nantes - Nantes - France	Stéphanie DIROU, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU Grenoble - Grenoble - France	Sebastien QUETANT, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU Nancy - Nancy - France	Anne GUILLAUMOT, MD	En recrutement		Contact (sur clinicalTrials)
CHU Nice - Nice - France	Sylvie LEROY, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU Reims - Reims - France	Francois LEBARGY, MD	En recrutement		Contact (sur clinicalTrials)
CHU Rennes - Rennes - France	Stephane JOUNEAU, MD	En recrutement		Contact (sur clinicalTrials)
CHU Rouen - Rouen - France	Stéphane DOMINIQUE, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU Strasbourg - Strasbourg - France	Sandrine HIRSCHI, MD	Recrutement non commencé		Contact (sur clinicalTrials)
CHU Toulouse - Toulouse - France	Gregoire PREVOT, MD	En recrutement		Contact (sur clinicalTrials)
CHU Tours - Tours - France	Thomas FLAMENT, MD	Recrutement non commencé		Contact (sur clinicalTrials)
Hôpital FOCH - Paris - France	Alexandre CHABROL, MD	Recrutement non commencé		Contact (sur clinicalTrials)
Hôpital Nord - Marseille - France	Martine REAYNAUD GAUBERT, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Saint-Louis - Paris - France	Abdellatif TAZI, MD	Recrutement non commencé		Contact (sur clinicalTrials)
Hospices Civils de Lyon - Lyon - France	Vincent COTTIN, MD	En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

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

Critère de non inclusion

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

NCT05674994 - Glucocorticoids Versus Placebo for the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis: a Randomized Controlled Trial (EXAFIP2)

Informations générales
Etablissements
Critères
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