Clinical evaluation plan outdated and obsolete due to altered clinical routine

The diagnosis of idiopathic pulmonary fibrosis (IPF) is currently one of the most common diagnoses for patients under evaluation for lung transplantation. In recent years, an absolute increase in prevalence/ incidence of IPF has been observed. There is evidence that patients with IPF on waiting list for lung transplantation might benefit from pirfenidone treatment. Until now, no data are published regarding this important issue in lung transplantation.

Primary objective is to determine whether there is a difference in the duration time of mechanical ventilation (weaning) directly after lung transplantation between patients treated with pirfenidone and patients without pirfenidone treatment. The Secondary objectives are to determine whether there are differences between the pirfenidone treatment group and the control group regarding survival after LUTX, the score on the Saint Georges Respiratory Questionnaire and the decline in forced vital capacity (FVC%) In this Investigator initiated, non- interventional single center study , patients on the waiting list for transplant pirfenidone treatment receive oral pirfenidone at the standard dose of 2403 mg per day. The treatment duration will range from 6 to 12 months. A control group will be used to correlate the outcome-parameters for a descriptive comparison. The control group includes patients with IPF on the waiting list who were on another IPF specific (or no) treatment for IPF The Study Population are Patients aged between 40-70 years who are admitted to the lung transplantation department and fulfill the international criteria for idiopathic pulmonary fibrosis ( existence of a usual interstitial pneumonia (UIP) pattern in the high-resolution computed tomography (HRCT) is necessary).

Variables: Duration of mechanical ventilation after LUTX (hours), Forced Vital capacity relative to reference value at baseline (FVC0%), Forced Vital capacity relative to reference value after 6 months (FVC6%),Forced Vital capacity relative to reference value after 12 months (FVC12%) Study Size: 30 patients in the Pirfenidone group, 20 patients in the control group.

For the primary Endpoint, the mean, standard deviation, median, minimum and maximum of the weaning time of patients who received a pirfenidone treatment, as well as of patients from the control group will be computed and presented in a table. Additionally, a Kaplan-Meier curve will be estimated and plotted alongside the respective 95% CI calculated using the method of Brookmeyer and Crowley. Furthermore, a stepwise linear regression using forward selection and Age, RBMI, FVC0%, (FVC6%-FVC0%), TLC, FEV1% and ECMO, as well as the pirfenidone treatment as predictors will be computed. The null hypothesis is that the pirfenidone treatment has no influence on the weaning time. The according model coefficient estimate and standard error will be used to test the null hypothesis using a t-test at significance level α=0.05.

For the secondary endpoints, the mean, standard deviation, median, minimum and maximum of patients who received a pirfenidone treatment, as well as of patients from the control group will be computed and presented in a tableStepwise Cox Regression using forward selection and Age, RBMI, FVC0%, (FVC6%-FVC0%) and ECMO, as well as the pirfenidone treatment as predictors will be computed in order to compare the treatment and the control group a . If p-values are calculated for the secondary endpoint analysis, they serve only descriptive purposes. Therefore no multiple testing corrections are applied.

Inclusion Criteria:

For Pirfenidone Group

Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study

• mild to moderate idiopathic pulmonary fibrosis (IPF).
• Current or intended treatment with Pirfenidone
• Diagnosis of Interstitial Lung disease
• Evaluation for Lung Transplantation
• Age 40-70

For Control Group

Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study

• mild to moderate idiopathic pulmonary fibrosis (IPF).
• Diagnosis of Interstitial Lung disease
• Evaluation for Lung Transplantation
• Age 40-70

Exclusion Criteria:

For Pirfenidone Group

• Other lung diseases (such as cystic fibrosis, COPD)
• Infection with Hepatitis C,
• Liver cirrhosis CHILD C
• Coronary heart disease (3VD)

For Control Group

• Other lung diseases (such as cystic fibrosis, COPD)
• Infection with Hepatitis C,
• Liver cirrhosis CHILD C
• Coronary heart disease (3VD)

All patients who are admitted to the lung transplantation department and fulfill the international criteria for idiopathic pulmonary fibrosis will be evaluated (existence of a usual interstitial pneumonia (UIP) pattern in the high-resolution computed tomography (HRCT) is necessary).

The assignment of a patient to a particular therapeutic strategy remains in the sole responsibility of the treating physician and must not be dictated by this study-specific observation- and evaluation plan