Managing progressive disease in idiopathic pulmonary fibrosis

Pragmatic Management of Progressive Disease in Idiopathic Pulmonary Fibrosis: a Randomized Trial

This study is testing if combining two approved medications for idiopathic pulmonary fibrosis can help patients whose disease keeps getting worse despite current treatments.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 378 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Hospices Civils de Lyon (other)
• Drugs / interventions: methotrexate, cyclophosphamide, prednisone
• Locations: 21 sites (Angers and 20 other locations)
• Trial ID: NCT03939520 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with progressive idiopathic pulmonary fibrosis (IPF) who continue to experience disease progression despite current treatments. It evaluates the effectiveness of combined therapies using pirfenidone and nintedanib, two approved medications for IPF. The study aims to provide guidance on managing patients who do not respond adequately to existing therapies, addressing a significant gap in treatment options. By assessing the impact of these therapies on disease progression, the trial seeks to improve patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are patients aged 50 and older diagnosed with idiopathic pulmonary fibrosis who have shown signs of disease progression despite antifibrotic treatment.

Not a fit: Patients who do not have idiopathic pulmonary fibrosis or those who have not experienced disease progression while on current therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management strategies for patients with progressive IPF, potentially enhancing their quality of life and survival rates.

How similar studies have performed: Other studies have shown success with similar approaches using antifibrotic therapies, but this specific combination and management strategy is relatively novel.

Eligibility criteria

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.

Exclusion Criteria:

* 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.

Where this trial is running

Angers and 20 other locations

• CHU d'Angers — Angers, France (RECRUITING)
• Centre Hospitalier de la côte Basque — Bayonne, France (NOT_YET_RECRUITING)
• CHRU de Besançon - Hôpital Jean Minjoz — Besançon, France (NOT_YET_RECRUITING)
• AP - HP - Hôpital Avicenne — Bobigny, France (RECRUITING)
• CHRU Hôpital Cavale Blanche — Brest, France (RECRUITING)
• Hôpital Pneumologique et Cardiovasculaire Louis Pradel — Bron, France (RECRUITING)
• CHU de Caen - Hôpital de la Côte de Nacre — Caen, France (RECRUITING)
• CHU Dijon Bourgogne - Hôpital François Mitterrand — Dijon, France (RECRUITING)
• CHRU de Lille - Hôpital Albert Calmette — Lille, France (RECRUITING)
• CHU de Marseille - Hôpital Nord — Marseille, France (RECRUITING)
• CHRU de Montpellier - Hôpital Arnaud de Villeneuve — Montpellier, France (RECRUITING)
• CHU - Hôpital G.R. Laennec — Nantes, France (RECRUITING)
• CHU de Nice, Hôpital Pasteur — Nice, France (RECRUITING)
• APHP - Hôpital Xavier Bichat-Claude Bernard — Paris, France (RECRUITING)
• Groupe Hospitalier Paris Saint Joseph — Paris, France (RECRUITING)
• Ch de Cornouaille — Quimper, France (NOT_YET_RECRUITING)
• CHU Rennes - Hôpital Pontchaillou — Rennes, France (RECRUITING)
• CHU de Toulouse - Hôpital Larrey — Toulouse, France (RECRUITING)
• CHRU, Tours - Hôpital Bretonneau — Tours, France (RECRUITING)
• CHU Nancy - Hôpital Brabois — Vandœuvre-lès-Nancy, France (RECRUITING)
• Hôpital Robert Schuman — Vantoux, France (RECRUITING)

Study contacts

• Principal investigator: Vincent COTTIN, Pr — Hospices Civils de Lyon
• Study coordinator: Vincent COTTIN, Pr

Conditions: Progressive Idiopathic Pulmonary Fibrosis, Pneumology, idiopathic pulmonary fibrosis, progressive disease, combined therapy, pirfenidone, nintedanib