Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF)
This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00517933
First received: August 15, 2007
Last updated: February 19, 2010
Last verified: February 2010
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Fibrosis Hypertension, Pulmonary |
Drug: Sildenafil Citrate Other: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis |
Resource links provided by NLM:
Genetics Home Reference related topics:
idiopathic pulmonary fibrosis
MedlinePlus related topics:
Exercise and Physical Fitness
High Blood Pressure
Pulmonary Fibrosis
Pulmonary Hypertension
U.S. FDA Resources
Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):
Primary Outcome 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Change in dyspnea [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]
- Change in quality of life [ Time Frame: Measured at Weeks 12 and 24 ] [ Designated as safety issue: No ]
- Change in 6-minute walk distance [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: No ]
| Enrollment: | 180 |
| Study Start Date: | August 2007 |
| Study Completion Date: | October 2009 |
| Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Sildenafil |
Drug: Sildenafil Citrate
Sildenafil citrate (20mg TID orally)
Other Name: Revatio
|
| Placebo Comparator: Placebo |
Other: Placebo
Placebo of sildenafil citrate (20mg TID orally)
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00517933
Locations
| United States, Alabama | |
| University of Alabama - Birmingham | |
| Birmingham, Alabama, United States, 35294 | |
| United States, California | |
| University of California - Los Angeles | |
| Los Angeles, California, United States, 90095 | |
| University of California - San Francisco | |
| San Francisco, California, United States, 94110 | |
| United States, Colorado | |
| National Jewish Medical and Research Center | |
| Denver, Colorado, United States, 80206 | |
| United States, Georgia | |
| Emory University | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| University of Chicago | |
| Chicago, Illinois, United States, 60637 | |
| United States, Louisiana | |
| Tulane University | |
| New Orleans, Louisiana, United States, 70118 | |
| United States, Michigan | |
| University of Michigan | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New York | |
| Weill Medical College of Cornell University | |
| New York, New York, United States, 10021 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Tennessee | |
| Vanderbilt University | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Washington | |
| University of Washington | |
| Seattle, Washington, United States, 98165 | |
Sponsors and Collaborators
Pfizer
Investigators
| Study Chair: | Gary Hunninghake, MD | University of Iowa |
| Principal Investigator: | Kevin Brown, MD | National Jewish Health |
| Principal Investigator: | Rob Kaner, MD | Weill Medical College at Cornell University |
| Principal Investigator: | Talmadge King, MD | University of California, San Francisco |
| Principal Investigator: | Joe Lasky, MD | Tulane University |
| Principal Investigator: | James Loyd, MD | Vanderbilt University |
| Principal Investigator: | Fernando Martinez, MD | University of Michigan |
| Principal Investigator: | Imre Noth, MD | University of Chicago |
| Principal Investigator: | Ganesh Raghu, MD | University of Washington |
| Principal Investigator: | Jesse Roman, MD | Emory University |
| Principal Investigator: | Jay Ryu, MD | Mayo Clinic |
| Principal Investigator: | David Zisman, MD | University of California, Los Angeles |
| Principal Investigator: | Kevin Anstrom, PhD | Duke University |
| Study Director: | Herbert Reynolds, MD | National Heart, Lung, and Blood Institute (NHLBI) |
| Principal Investigator: | Lake D Morrison, MD | Duke University |
More Information
Additional Information:
No publications provided by National Heart, Lung, and Blood Institute (NHLBI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Dr. Kevin J. Anstrom, Principal Investigator DCC, Duke Clinical Research Institute |
| ClinicalTrials.gov Identifier: | NCT00517933 History of Changes |
| Other Study ID Numbers: | 507, 5 U10 HL080413-01 |
| Study First Received: | August 15, 2007 |
| Last Updated: | February 19, 2010 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
|
Idiopathic Pulmonary Fibrosis Pulmonary Hypertension |
Additional relevant MeSH terms:
|
Fibrosis Hypertension Hypertension, Pulmonary Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Pathologic Processes Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Idiopathic Interstitial Pneumonias |
Lung Diseases, Interstitial Sildenafil Vasodilator Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 17, 2013