Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00517933 |
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Recruitment Status :
Completed
First Posted : August 17, 2007
Results First Posted : August 23, 2013
Last Update Posted : June 24, 2015
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Fibrosis Hypertension, Pulmonary | Drug: Sildenafil Citrate Other: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 180 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis |
| Study Start Date : | August 2007 |
| Actual Primary Completion Date : | May 2009 |
| Actual Study Completion Date : | October 2009 |
| Arm | Intervention/treatment |
|---|---|
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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
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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 |
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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
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Other: Placebo
Placebo (20mg TID orally for 12 weeks followed by 20mg open-label sildenafil for 12 weeks) |
- Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement) [ Time Frame: Measured at Week 12 ]This is a binary score (1 or 0) with 1 being better than 0. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- 6-minute Walk Distance (6MWT) [ Time Frame: Baseline, 6 week, 12 week ]The 6MWT measures the distance that a participant can walk in a period of 6 minutes.
- Estimated Change From Baseline to 12 Weeks in 6-minute Walk Distance [ Time Frame: Baseline, week 12 ]The 6MWT measures the distance that a participant can walk in a period of 6 minutes. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Desaturation During 6-minute Walk Test (6MWT) [ Time Frame: Week 12 ]The 6MWT was stopped when the pulse oximetry (SpO2) dropped to below 80% for six consecutive seconds. The estimates are based on the Kaplan-Meier event curves with minutes walked as the x-axis.
- Change in Dyspnea [ Time Frame: Measured from enrollment to 12 weeks (phase I) ]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.
- University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total [ Time Frame: Baseline, 6 weeks, 12 weeks ]
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. (Raw scores)
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Change in Forced Vital Capacity (FVC) Adjusted Values [ Time Frame: Baseline, Week 12 ]Change in FVC (liters) from baseline (time 0) to week 12 comparing the sildenafil and placebo groups. Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Forced Vital Capacity (FVC) [ Time Frame: Baseline, Week 6, Week 12 ]Raw scores of FVC (liters) from baseline (time 0) to week 6 and 12 comparing the sildenafil and placebo groups
- Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted Values [ Time Frame: Baseline, Week 12 ]Change in DLCO (% predicted) measured at baseline (time 0), and week 12 comparing the sildenafil and placebo groups. All models adjust for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) [ Time Frame: Baseline, Week 6, Week 12 ]Raw scores of DLCO (% predicted) measured at baseline (time 0), week 6, and week 12 comparing the sildenafil and placebo groups
- Change in Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Adjusted Values) [ Time Frame: Baseline, 12 week ]The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test. Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores) [ Time Frame: Baseline, 6 week, 12 week ]The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum) and indicates the degree of breathlessness after completion of the 6-minute walk test.
- Change in St. George's Respiratory Questionnaire (Total Score) (Adjusted Values) [ Time Frame: Baseline, 12 week ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment.) Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- St. George's Respiratory Questionnaire (Total Score) [ Time Frame: Baseline, 6 weeks, 12 weeks ]Mean raw scores of the St. George's Respiratory Questionnaire. The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment.)
- Change in St. George's Respiratory Questionnaire (Symptoms Score) Adjusted Value [ Time Frame: Baseline, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- St. George's Respiratory Questionnaire (Symptoms Score) [ Time Frame: Baseline, 6 weeks, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire. Mean raw scores of the St. George's Respiratory Questionnaire.
- Change in St. George's Respiratory Questionnaire (Activity Score) Adjusted Value [ Time Frame: Baseline, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- St. George's Respiratory Questionnaire (Activity Score) [ Time Frame: Baseline, 6 weeks, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire.
- Change in St. George's Respiratory Questionnaire (Impacts Score) Adjusted Value [ Time Frame: Baseline, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- St. George's Respiratory Questionnaire (Impacts Score) [ Time Frame: Baseline, 6 weeks, 12 weeks ]The St. George's Respiratory Questionnaire asks patients how breathing problems impair their life and is scored from 0 (no impairment) to 100 (maximum impairment). Mean raw scores of the St. George's Respiratory Questionnaire.
- Change in ICECAP-O Adjusted Value [ Time Frame: Baseline, 12 weeks ]
The ICEpop CAPability measure for Older people (ICECAP-O) is a measure of capability in older people for use in economic evaluation. The values of ICECAP-O range from 0 (worst) to 1 (best).
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- ICECAP-O [ Time Frame: Baseline, 6 weeks, 12 weeks ]The ICEpop CAPability measure for Older people (ICECAP-O) is a measure of capability in older people for use in economic evaluation. The values of ICECAP-O range from 0 (worst) to 1 (best). Mean raw scores of ICECAP-O.
- Change in EuroQOL Thermometer (Adjusted Value) [ Time Frame: Baseline, 12 weeks ]
The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate a better health state.
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- EuroQOL Thermometer [ Time Frame: Baseline, 6 weeks, 12 weeks ]
The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher scores indicate a better health state.
Mean raw scores of EuroQOL Thermometer.
- Change in EuroQOL (EQ-5D) Utility - Adjusted Value [ Time Frame: Baseline, 12 weeks ]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- EuroQOL (EQ-5D) Utility [ Time Frame: Baseline, 6 weeks, 12 weeks ]
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state.
Mean raw scores of EuroQOL Utility.
- Change in Short Form Health Survey (SF36) General Health - Adjusted Value [ Time Frame: Baseline, 12 weeks ]
The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.
Each score ranges from 0 to 100, with a higher score indicating better function.
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Short Form Health Survey (SF36) General Health [ Time Frame: Baseline, 6 weeks, 12 weeks ]
The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.
Each score ranges from 0 to 100, with a higher score indicating better function.
Mean raw scores of SF36 General Health
- Change in SF36 Aggregate Physical (Adjusted Value) [ Time Frame: Baseline, 12 weeks ]
The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.
Each score ranges from 0 to 100, with a higher score indicating better function.
Values adjusted for baseline values of age, height, sex, white race, and DLCO. Values from models are estimated changes from baseline to 12 weeks (with 95% confidence intervals). The difference estimate is based on sildenafil - placebo.
- Short Form Health Survey (SF36) Aggregate Physical [ Time Frame: Baseline, 6 weeks, 12 weeks ]
The SF36 measures functional health and well-being scores on eight scales that correlate with two aggregate scores.
Each score ranges from 0 to 100, with a higher score indicating better function.
Mean raw scores of SF36 Aggregate Physical.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00517933
| 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 | |
| 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 |
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00517933 |
| Other Study ID Numbers: |
Pro00018538 U10HL080413 ( U.S. NIH Grant/Contract ) 507 |
| First Posted: | August 17, 2007 Key Record Dates |
| Results First Posted: | August 23, 2013 |
| Last Update Posted: | June 24, 2015 |
| Last Verified: | June 2015 |
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Idiopathic Pulmonary Fibrosis Pulmonary Hypertension |
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Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Hypertension, Pulmonary Hypertension Fibrosis Vascular Diseases Cardiovascular Diseases Pathologic Processes Lung Diseases |
Respiratory Tract Diseases Sildenafil Citrate Molecular Mechanisms of Pharmacological Action Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Urological Agents |