Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis

Inclusion Criteria:

• Clinical diagnosis of IPF

• Diffusing capacity of the lung (DLCO) level less than 35% (adjusted for hemoglobin)

Exclusion Criteria:

• Current enrollment in another investigational study

• Six-minute walk distance of less than 50 meters at screening or study entry

• Difference of greater than 15% between the screening and study entry 6-minute walkdistance

• Acute or long-term impairment other than dyspnea (e.g., angina pectoris, intermittentclaudication) that limits the ability to comply with the 6-minute walk test or otherstudy requirements

• Forced Expiratory Volume 1-second (FEV1)/forced vital capacity (FVC) ratio of lessthan 0.65 after bronchodilator use

• Extent of emphysema greater than the extent of fibrotic change (e.g., honeycombing,reticular changes) on high-resolution computed tomography (HRCT) scan

• Acute heart attack within the 6 months prior to study entry

• Nitrate use

• Hypersensitivity to sildenafil or any component of the formulation

• Presence of aortic stenosis (AS)

• Life-threatening arrhythmia within 1 month of study entry

• Diabetes mellitus requiring insulin therapy

• Second-degree or third-degree atrioventricular (AV) block on electrocardiogram

• Severe chronic heart failure, defined by left ventricular ejection fraction (LVEF) ofless than 25%

• Presence of idiopathic hypertrophic subaortic stenosis (IHSS)

• Hypotension (i.e., systolic blood pressure [SBP] less than 100 mm Hg or diastolicblood pressure [DBP] less than 50 mm Hg)

• Uncontrolled systemic hypertension (i.e., SBP greater than 180 mm Hg or DBP greaterthan 100 mm Hg)

• Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma,leukemia) that may predispose participant to priapism

• Aspartate aminotransferase (AST), serum glutamic pyruvic transaminase (SGPT), alanineaminotransferase (ALT), or serum glutamic oxaloacetic transaminase (SGOT) greater thanthree times the upper limit of normal range

• Kidney impairment (i.e., creatinine clearance less than 30 mL/minute)

• Current drug or alcohol dependence

• Retinitis pigmentosa

• History of vision loss

• History of nonarteritic ischemic optic neuropathy

• Recently initiated pulmonary rehabilitation within 30 days of study entry.Participants will be prohibited from starting pulmonary rehabilitation during thestudy. Participants who are currently undergoing maintenance pulmonary rehabilitationat study entry will be asked to maintain their levels of rehabilitation for theduration of the study.

• Use of any investigational therapy as part of a clinical trial for any medicalcondition within 30 days of study entry

• Start or change in dose of treatment for IPF investigational agent (e.g., interferongamma-1b, pirfenidone, etanercept, N-acetylcysteine, any other investigational agentintended to treat IPF), corticosteroids, or cytotoxic agents within 30 days of studyentry

• Use of certain medications. More information about this criterion can be found in thestudy protocol.

• Treatment for pulmonary hypertension with prostaglandins (e.g., epoprostenol,treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), orany other phosphodiesterase inhibitor (e.g., tadalafil, vardenafil) within 30 days ofstudy entry

• Addition or discontinuation of calcium channel blockers, digitalis, diuretics, orvasodilators within 30 days of study entry (dosage must be stable for 7 days prior tostudy entry [except for diuretics])

• Currently on the waiting list for a lung transplant

• Use of L-arginine supplements

• Use of grapefruit juice or St. John's wort

• Pregnant or breastfeeding

• Resting saturation of peripheral oxygen (SpO2) (i.e., oxygen saturation measured usingpulse oximetry) less than 92% with 6 liters of supplemental oxygen