This is a randomized, double-blind, placebo-controlled trial of an experimental anti-fibrotic drug, pirfenidone in early stage usual interstitial pneumonitis (UIP), the most common form of idiopathic pulmonary fibrosis (IPF). Patients will receive either high dose pirfenidone, low dose pirfenidone, or placebo. Pirfenidone will be given by pill form three times a day for 60 weeks (14 months) with periodic measurement of pulmonary function tests and blood tests. The study will enroll 585 patients at 125 clinical sites world-wide, including The Ohio State University Medical Center.
1. Dyspnea on exertion for 3 or more months.
2. Diagnosis of IPF within the past 4 years.
3. Age 40 - 80 years.
4. High resolution chest CT scan consistent with usual interstitial pneumonitis.
5. For patients < 50 years old, a surgical lung biopsy showing definite or probable usual interstitial pneumonitis within the past 4 years; for patients > 50 years old, a surgical lung biopsy is not required but a bronchoalveolar lavage (BAL) and/or transbronchial biopsy must be done if there is no surgical lung biopsy in order to exclude other lung diseases.
6. FVC greater than or equal to 50% of predicted (using Hankinson normal value data set).
7. Hemoglobin-corrected diffusing capacity greater than or equal to 35% of predicted (using Crapo normal value data set).
8. Either FVC or DLCO less than or equal to 90% of predicted.
9. No evidence of improvement in IPF over the past year.
10. Able to walk at least 492 feet during a 6 minute walk test with an oxygen saturation of greater than or equal to 83% while breathing no more than 6 liters of oxygen per nasal cannula.
1. Premature withdrawl from any randomized IPF trial within the past 2 years.
2. FEV1/FVC ratio < 0.7 after bronchodilator.
3. Positive bronchodilator response defined by an increase in FEV1 or FVC of > 12% after a bronchodilator challenge.
4. Change in FVC more than 10% between screening visit and study initiation date.
5. Residual volume > 120% of predicted (using Crapo normal value data set).
6. Clinically significant exposure to occupational agents known to cause interstitial lung disease (eg, asbestos, birds, etc.).
7. Known explanation for interstitial lung disease (eg, radiation, viral hepatitis, radiation, sarcoidosis, HIV).
8. Diagnosis of any connective tissue disease (eg, lupus, scleroderma, rheumatoid arthritis).
9. Clinical evidence of any active infection.
10. Currently on a lung transplant waiting list.
11. Inability to undergo pulmonary function tests.
12. Any malignancy likely to cause death within the next 2 years.
13. Any medical condition likely to cause death within the next 2 years.
14. History of advanced cirrhosis or clinically significant liver disease.
15. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) in the past 6 months including: myocardial infarction, coronary artery bypass surgery, coronary angioplasty, unstable angina, congestive heart failure requiring hospitalization, uncontrolled arrhythmias, or asthma or chronic bronchitis requiring hospitalization in the past 6 months.
16. Uncontrolled diabetes (hemoglobin A1C > 10).
17. Pregnancy or lactation.
18. Alcohol or drug abuse in the past 2 years.
19. Any habit or medical condition associated with loss of consciousness or aspiration in the past 2 years.
20. Family or personal history of long QT syndrome.
21. Abnormal liver enzymes: total bilirubin, ALT, AST, or ALP > 2.5 times upper limit of normal.
22. QTcB interval > 500 msec.
23. Prior use of pirfenidone or known hypersensitivity to pirfenidone.
24. Any investigational treatment for IPF within the 28 days prior to the screening visit.
25. Immunosuppressive therapy for IPF within the 28 days prior to the screening visit (prednisone, cyclophosphamide, methotrexate, azathioprine, cyclosporine, etc.).
26. Cytokine modulator medications (eg, etanercept) within the 28 days prior to the screening visit.
27. Any off-label treatment for IPF (eg, gamma interferon, N-acetylcysteine, imatinib mesylate, colchicine, bosentan, etc.) within the 28 days prior to the screening visit.
Patients can be evaluated for their pulmonary fibrosis (including eligibility for the CAPACITY trial) by having them seen in consultation in the Interstitial Lung Disease Clinic by either Dr. Allen or Dr. Bhatt. To schedule an appointment, call 614-293-4925.