Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF)

Duke University

Status and phase

Completed

Phase 3

Conditions

Pulmonary Fibrosis

Hypertension, Pulmonary

Treatments

Drug: Sildenafil Citrate

Other: Placebo

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00517933

Pro00018538

U10HL080413 (U.S. NIH Grant/Contract)

507

Details and patient eligibility

About

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.

Full description

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.

Enrollment

180 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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