Informations générales (source: ClinicalTrials.gov)
Pragmatic Management of Progressive Disease in Idiopathic Pulmonary Fibrosis: a Randomized Trial (PROGRESSION)
Interventional
Phase 4
Hospices Civils de Lyon (Voir sur ClinicalTrials)
juin 2020
janvier 2026
29 juin 2024
Idiopathic pulmonary fibrosis (IPF) is a prototype of chronic, progressive, and fibrotic
lung disease. It has been considered rare, with an incidence estimated to 11.5 cases per
100 000 individuals per year. Increasing rates of hospital admissions and deaths due to
IPF suggest an increasing burden of disease. The median survival time from diagnosis is
2-4 years.
Recently two disease-modifying therapies, pirfenidone and nintedanib, have been approved
worldwide. Both drugs reduce the disease progression as measured by progressive decline
in forced vital capacity (FVC), with a reduction of overall mortality showed by
meta-analysis of phase III pirfenidone trials.
However, progression of disease continues to occur despite the currently available drug
therapy. Many patients die from progressive, chronic hypoxemic respiratory failure, or
less frequently from acute exacerbation of pulmonary fibrosis. In these patients, no data
are available to guide management between continuation of the prescribed antifibrotic
drug, to switch to the other available antifibrotic drug, or to combine the available
drugs.
The combination of nintedanib and pirfenidone is not recommended outside clinical trials.
However, although both antifibrotic drugs were developed and approved as monotherapy, two
recent trials have suggested the feasibility and safety of combining them over a 12-24
weeks period. These results encourage further studies of combination treatment with
pirfenidone and nintedanib in patients with IPF. Such study is timely, as there is a risk
that clinicians facing the continued worsening of disease in patients receiving one of
the available drugs may prescribe both drugs combined outside clinical trials,
potentially exposing patients to a currently unknown risk.
This study will evaluate the efficacy and tolerance of the combination pirfenidone and
nintedanib as compared to a "switch monotherapy": i.e. switching from the current to the
other of the two existing drugs prescribed as monotherapy, in patients who present
chronic worsening IPF despite receiving either pirfenidone or nintedanib and as to a
"control group": i.e.treatment still be on as before randomization (pirfenidone or
nintedanib).
Etablissements
| 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 | Contact (sur clinicalTrials) | |||
| GH PARIS SITE SAINT JOSEPH | Jean-Marc NACCACHE | Contact (sur clinicalTrials) | |||
| IFSI AVICENNE (AP-HP) | Hilario NUNES | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHRU de Montpellier - Hôpital Arnaud de Villeneuve - Montpellier - France | Anne-Sophie GAMEZ | Contact (sur clinicalTrials) | |||
| CHRU Hôpital Cavale Blanche - Brest - France | Aude BARNIER | Contact (sur clinicalTrials) | |||
| CHU - Hôpital G.R. Laennec - Nantes - France | Stéphanie DIROU | Contact (sur clinicalTrials) | |||
| CHU d'Angers - Angers - France | Frédéric GAGNADOUX | Contact (sur clinicalTrials) | |||
| CHU de Caen - Hôpital de la Côte de Nacre - Caen - France | Emmanuel BERGOT | Contact (sur clinicalTrials) | |||
| CHU de Marseille - Hôpital Nord - Marseille - France | Martine REYNAUD-GAUBERT | Contact (sur clinicalTrials) | |||
| CHU de Nice, Hôpital Pasteur - Nice - France | Charles-Hugo MARQUETTE | 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 | |||||
| Centre Hospitalier de la côte Basque - Bayonne - France | Pierre RIGAUD | Contact (sur clinicalTrials) | |||
| Ch de Cornouaille - Quimper - France | Nicolas BIZIEN, Dr | Contact (sur clinicalTrials) | |||
| CHRU de Besançon - Hôpital Jean Minjoz - Besançon - France | Mathilde DUPREZ | Contact (sur clinicalTrials) | |||
| CHRU de Lille - Hôpital Albert Calmette - Lille - France | Lidwine WEMEAU-STERVINOU | Contact (sur clinicalTrials) | |||
| CHRU, Tours - Hôpital Bretonneau - Tours - France | Laurent PLANTIER | Contact (sur clinicalTrials) | |||
| CHU de Toulouse - Hôpital Larrey - Toulouse - France | Grégoire PRÉVOT | Contact (sur clinicalTrials) | |||
| CHU Dijon Bourgogne - Hôpital François Mitterrand - Dijon - France | Philippe BONNIAUD | Contact (sur clinicalTrials) | |||
| CHU Nancy - Hôpital Brabois - Vandœuvre-lès-Nancy - France | Anne GUILLAUMOT | Contact (sur clinicalTrials) | |||
| CHU Rennes - Hôpital Pontchaillou - Rennes - France | Stéphane JOUNEAU | Contact (sur clinicalTrials) | |||
| Hôpital Pneumologique et Cardiovasculaire Louis Pradel - Bron - France | Vincent Cottin, Pr | Contact (sur clinicalTrials) | |||
| Hôpital Robert Schuman - Vantoux - France | Benoit GODBERT | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patient aged ≥ 50 years.
- Patient with Idiopathic Pulmonary Fibrosis satisfying the ATS/ERS/JRS/ALAT
diagnostic criteria (29) diagnosed.
In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must
be "consistent with Usual Interstitial Pneumonia (UIP)" defined as meeting either
criteria A, B, and C, or criteria A and C, or criteria B and C below:
A. Definite honeycomb lung destruction with basal and peripheral predominance. B.
Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis,
with basal and peripheral predominance.
C. Atypical features are absent, specifically nodules and consolidation. Ground glass
opacity, if present, is less extensive than reticular opacity pattern.
-
- Patient who fulfill at least 1 of the 4 criteria for IPF progression in the 12
months (+/- one six months) before screening, despite antifibrotic treatment in
clinical practice (if yes check the option(s)). These criteria are: 0 Relative
decline in FVC ≥10% predicted 0 Relative decline in FVC ≥5-<10% predicted and
worsened respiratory symptoms 0 Relative decline in FVC ≥5-<10% predicted and
increased extent of fibrotic changes on chest imaging 0 Worsened respiratory
symptoms and increased extent of fibrotic changes on chest imaging
- Patient must have been on a stable dose of pirfenidone or nintedanib prescribed as
first-line therapy for at least 6 months, with good tolerance of 1602 to 2403 mg per
day of pirfenidone or 200 to 300 mg per day of nintedanib.
- Patient who has a FVC ≥ 45% of predicted.
- Patient who has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.
- Patient who has a life expectancy of at least 9 months.
- Patient who has provided his written informed consent to participate in the study.
- Patient affiliated to a social insurance regimen.
- Patient aged ≥ 50 years.
- Patient with Idiopathic Pulmonary Fibrosis satisfying the ATS/ERS/JRS/ALAT
diagnostic criteria (29) diagnosed.
In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must
be "consistent with Usual Interstitial Pneumonia (UIP)" defined as meeting either
criteria A, B, and C, or criteria A and C, or criteria B and C below:
A. Definite honeycomb lung destruction with basal and peripheral predominance. B.
Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis,
with basal and peripheral predominance.
C. Atypical features are absent, specifically nodules and consolidation. Ground glass
opacity, if present, is less extensive than reticular opacity pattern.
-
- Patient who fulfill at least 1 of the 4 criteria for IPF progression in the 12
months (+/- one six months) before screening, despite antifibrotic treatment in
clinical practice (if yes check the option(s)). These criteria are: 0 Relative
decline in FVC ≥10% predicted 0 Relative decline in FVC ≥5-<10% predicted and
worsened respiratory symptoms 0 Relative decline in FVC ≥5-<10% predicted and
increased extent of fibrotic changes on chest imaging 0 Worsened respiratory
symptoms and increased extent of fibrotic changes on chest imaging
- Patient must have been on a stable dose of pirfenidone or nintedanib prescribed as
first-line therapy for at least 6 months, with good tolerance of 1602 to 2403 mg per
day of pirfenidone or 200 to 300 mg per day of nintedanib.
- Patient who has a FVC ≥ 45% of predicted.
- Patient who has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.
- Patient who has a life expectancy of at least 9 months.
- Patient who has provided his written informed consent to participate in the study.
- Patient affiliated to a social insurance regimen.
- Patients under judicial protection.
- Female patient who is pregnant or lactating, or is of child bearing potential
(defined as a sexually mature woman not surgically sterilized or not post-menopausal
for at least 24 consecutive months if ≤ 55 years or 12 months if > 55 years) and who
did not agree to use highly effective methods of birth control throughout the study.
- Patient who is currently on both pirfenidone and nintedanib.
- Patient who has already received pirfenidone and nintedanib either concomitantly or
successively.
- Patient who has a contra-indication to pirfenidone or nintedanib.
- Patient who has emphysema > 15% on HRCT or the extent of emphysema is greater than
the extent of fibrosis according to reported results from the most recent HRCT.
- Patient who had acute exacerbation of idiopathic pulmonary fibrosis within the
previous 3 months.
- Patient who has a history of cigarette smoking within the previous 3 months.
- Patient who has received experimental therapy for IPF within 4 weeks before
baseline.
- Patient who is receiving systemic corticosteroids equivalent to prednisone > 15
mg/day or equivalent within 2 weeks before baseline.
- Patient who received Immuno-suppressants (e.g. methotrexate, azathioprine,
cyclophosphamide, cyclosporine, sirolimus, everolimus or other immunosuppressants)
within 4 weeks before baseline.
- Patient who has a history of a malignancy within the previous 5 years, with the
exception of basal cell skin neoplasms. In addition, a malignant diagnosis or
condition first occurring prior to 5 years must be considered cured, inactive, and
not under current treatment.
- Patient who, in the Investigator's opinion, is not able to perform home spirometry
in accordance with the protocol.
- Patient who has any concurrent condition other than IPF that, in the Investigator's
opinion, is unstable and/or would impact the likelihood of survival for the study
duration or the subject's ability to complete the study as designed, or may
influence any of the safety or efficacy assessments included in the study.
- Patient who has baseline resting oxygen saturation of < 88% on room air or
supplemental oxygen.
- Patient who had lung transplantation or who is on a lung transplant list and the
investigator anticipates the patient will not be able to complete the study prior to
transplant.