Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
Condition: Pulmonary Fibrosis; Hypertension, Pulmonary
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Hypertension, Pulmonary; Hypertension; Fibrosis
Intervention: Sildenafil Citrate; Placebo
Intervention description: Sildenafil citrate (20mg 3 times a day [TID] orally for 12 weeks followed by 20mg TID open-label sildenafil for an additional 12 weeks); Placebo (20mg TID orally for 12 weeks followed by 20mg open-label sildenafil for 12 weeks)
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 180.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Idiopathic Pulmonary Fibrosis; Pulmonary Hypertension

Summary:

      Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that affects an individual's
      ability to breathe. This study will evaluate the effectiveness of sildenafil, a medication
      that increases blood flow to the lungs, at improving breathing function, exercise capacity,
      and quality of life in people with advanced IPF.
    

Eligibility criteria:

        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 walk
             distance

          -  Acute or long-term impairment other than dyspnea (e.g., angina pectoris, intermittent
             claudication) that limits the ability to comply with the 6-minute walk test or other
             study requirements

          -  Forced Expiratory Volume 1-second (FEV1)/forced vital capacity (FVC) ratio of less
             than 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) of
             less than 25%

          -  Presence of idiopathic hypertrophic subaortic stenosis (IHSS)

          -  Hypotension (i.e., systolic blood pressure [SBP] less than 100 mm Hg or diastolic
             blood pressure [DBP] less than 50 mm Hg)

          -  Uncontrolled systemic hypertension (i.e., SBP greater than 180 mm Hg or DBP greater
             than 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), alanine
             aminotransferase (ALT), or serum glutamic oxaloacetic transaminase (SGOT) greater than
             three 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 the
             study. Participants who are currently undergoing maintenance pulmonary rehabilitation
             at study entry will be asked to maintain their levels of rehabilitation for the
             duration of the study.

          -  Use of any investigational therapy as part of a clinical trial for any medical
             condition within 30 days of study entry

          -  Start or change in dose of treatment for IPF investigational agent (e.g., interferon
             gamma-1b, pirfenidone, etanercept, N-acetylcysteine, any other investigational agent
             intended to treat IPF), corticosteroids, or cytotoxic agents within 30 days of study
             entry

          -  Use of certain medications. More information about this criterion can be found in the
             study protocol.

          -  Treatment for pulmonary hypertension with prostaglandins (e.g., epoprostenol,
             treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), or
             any other phosphodiesterase inhibitor (e.g., tadalafil, vardenafil) within 30 days of
             study entry

          -  Addition or discontinuation of calcium channel blockers, digitalis, diuretics, or
             vasodilators within 30 days of study entry (dosage must be stable for 7 days prior to
             study 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 using
             pulse oximetry) less than 92% with 6 liters of supplemental oxygen