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).

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.