Official Title: “Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2009

IPF is a disease in which fibrous tissue clogs the lungs. This eventually damages air sacs in the lungs and leads to widespread and permanent scarring of lung tissue. Individuals with IPF may experience breathing difficulties, cough, chest pain, and a decreased exercise capacity.

Pulmonary hypertension, which is high blood pressure in the arteries of the lungs, affects half of all people with IPF. The fibrous tissue that clogs the lungs also blocks blood from flowing through the lungs effectively, reducing the amount of oxygen in the lungs. The fibrous tissue also reduces the lungs' ability to use what oxygen is available. These factors can cause breathing difficulties and may eventually lead to heart disease. Sildenafil is a medication that can increase blood supply to the lungs and reduce the heart's workload. The purpose of this study is to evaluate the effectiveness of sildenafil at improving breathing function, exercise capacity, and quality of life in people with advanced IPF.

This study will enroll people with advanced IPF. Participants will be randomly assigned to receive sildenafil or placebo three times a day for 12 weeks. Study visits will occur at baseline and Weeks 1, 6, and 12. At Week 12, participants will have the option to continue in the study for an additional 12 weeks. All participants who agree to continue in the study will receive sildenafil three times a day for the second 12 weeks. Study visits will occur at Weeks 13, 18, and 24. At all study visits, a physical exam and blood collection will occur.

At selected visits, the following study procedures will occur: lung function testing; urine collection; a 6-minute walk test, which will measure the distance walked in a 6-minute period; and questionnaires to assess health status, breathing, and quality of life.

Participants will record medication usage and symptoms in a daily diary. Study researchers will review medical records and the Social Security death index 5 years following the end of the study to determine the incidence of death among study participants.

Intervention(s) in this Clinical Trial

• Drug: Sildenafil Citrate
  • Sildenafil citrate (20mg TID orally)
• Other: Placebo
  • Placebo of sildenafil citrate (20mg TID orally)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Sildenafil
• Placebo Comparator: Placebo

Primary Measures

• Change in 6-minute walk distance (defined as greater than or equal to 20% improvement or less than 20% improvement)
  • Time Frame: Measured at Week 12
    Safety Issue?: No

Secondary Measures

• Change in dyspnea
  • Time Frame: Measured at Weeks 12 and 24
    Safety Issue?: No
• Change in oxygen desaturation measures (time, distance, recovery time) during 6-minute walk test
  • Time Frame: Measured at Weeks 12 and 24
    Safety Issue?: No
• Change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO)
  • Time Frame: Measured at Weeks 12 and 24
    Safety Issue?: No
• Change in quality of life
  • Time Frame: Measured at Weeks 12 and 24
    Safety Issue?: No
• Change in 6-minute walk distance
  • Time Frame: Measured at Week 24
    Safety Issue?: No

Inclusion Criteria:

• Clinical diagnosis of IPF
• 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
• FEV1/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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Gary Hunninghake, MD Study Chair University of Iowa  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00517933

Study ID Number: 507

ClinicalTrials.gov Identifier: NCT00517933

Health Authority: United States: Federal Government

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