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

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00517933
First received: August 15, 2007
Last updated: August 4, 2014
Last verified: January 2013
  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:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement) [ Time Frame: Measured at Week 12 ] [ Designated as safety issue: No ]
    This is a binary score (1 or 0) with 1 being better than 0.


Secondary Outcome Measures:
  • Change in Dyspnea [ Time Frame: Measured from enrollment to 12 weeks (phase I) ] [ Designated as safety issue: No ]
    The University of California at San Diego Shortness of Breath Questionnaire (SOBQ) uses a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness") to rate 24 items. The final score ranges from 0 to 120 -- lower scores are better.

  • Change in Oxygen Desaturation Measures (Time, Distance, Recovery Time) During 6-minute Walk Test [ Time Frame: Measured at Week 12 ] [ 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 Week 12 ] [ 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
Active Comparator: Sildenafil
20 mg of sildenafil 3 times a day (TID) for 12 weeks followed by 20 mg of sildenafil TID for an additional 12 weeks
Drug: Sildenafil Citrate
Sildenafil citrate (20mg 3 times a day [TID] orally for 12 weeks followed by 20mg TID open-label sildenafil for an additional 12 weeks)
Other Name: Revatio
Placebo Comparator: Placebo / Sildanafil
20 mg of placebo TID for 12 weeks followed by 20 mg of sildenafil citrate TID for an additional 12 weeks
Other: Placebo
Placebo (20mg TID orally for 12 weeks followed by 20mg open-label sildenafil for 12 weeks)

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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Duke University
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 Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00517933     History of Changes
Other Study ID Numbers: Pro00018538, U10HL080413, 507
Study First Received: August 15, 2007
Results First Received: November 5, 2010
Last Updated: August 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Duke University:
Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension

Additional relevant MeSH terms:
Hypertension
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
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
Urological Agents

ClinicalTrials.gov processed this record on October 01, 2014