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

Primary Purpose

Pulmonary Fibrosis, Hypertension, Pulmonary

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Sildenafil Citrate
Placebo
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Fibrosis focused on measuring Idiopathic Pulmonary Fibrosis, Pulmonary Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Alabama - Birmingham
  • University of California - Los Angeles
  • University of California - San Francisco
  • National Jewish Medical and Research Center
  • Emory University
  • University of Chicago
  • Tulane University
  • University of Michigan
  • Mayo Clinic
  • Weill Medical College of Cornell University
  • Duke University Medical Center
  • Vanderbilt University
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sildenafil

Placebo / Sildanafil

Arm Description

20 mg of sildenafil 3 times a day (TID) for 12 weeks followed by 20 mg of sildenafil TID for an additional 12 weeks

20 mg of placebo TID for 12 weeks followed by 20 mg of sildenafil citrate TID for an additional 12 weeks

Outcomes

Primary Outcome Measures

Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement)
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.

Secondary Outcome Measures

6-minute Walk Distance (6MWT)
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
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)
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
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
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
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)
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
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)
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)
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)
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)
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)
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
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)
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
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)
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
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)
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
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
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)
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
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
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
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
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
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)
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
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.

Full Information

First Posted
August 15, 2007
Last Updated
June 22, 2015
Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00517933
Brief Title
Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
Acronym
STEP-IPF
Official Title
Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Fibrosis, Hypertension, Pulmonary
Keywords
Idiopathic Pulmonary Fibrosis, Pulmonary Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil
Arm Type
Active Comparator
Arm Description
20 mg of sildenafil 3 times a day (TID) for 12 weeks followed by 20 mg of sildenafil TID for an additional 12 weeks
Arm Title
Placebo / Sildanafil
Arm Type
Placebo Comparator
Arm Description
20 mg of placebo TID for 12 weeks followed by 20 mg of sildenafil citrate TID for an additional 12 weeks
Intervention Type
Drug
Intervention Name(s)
Sildenafil Citrate
Other Intervention Name(s)
Revatio
Intervention Description
Sildenafil citrate (20mg 3 times a day [TID] orally for 12 weeks followed by 20mg TID open-label sildenafil for an additional 12 weeks)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo (20mg TID orally for 12 weeks followed by 20mg open-label sildenafil for 12 weeks)
Primary Outcome Measure Information:
Title
Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement)
Description
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.
Time Frame
Measured at Week 12
Secondary Outcome Measure Information:
Title
6-minute Walk Distance (6MWT)
Description
The 6MWT measures the distance that a participant can walk in a period of 6 minutes.
Time Frame
Baseline, 6 week, 12 week
Title
Estimated Change From Baseline to 12 Weeks in 6-minute Walk Distance
Description
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.
Time Frame
Baseline, week 12
Title
Desaturation During 6-minute Walk Test (6MWT)
Description
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.
Time Frame
Week 12
Title
Change in Dyspnea
Description
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.
Time Frame
Measured from enrollment to 12 weeks (phase I)
Title
University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in Forced Vital Capacity (FVC) Adjusted Values
Description
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.
Time Frame
Baseline, Week 12
Title
Forced Vital Capacity (FVC)
Description
Raw scores of FVC (liters) from baseline (time 0) to week 6 and 12 comparing the sildenafil and placebo groups
Time Frame
Baseline, Week 6, Week 12
Title
Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted Values
Description
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.
Time Frame
Baseline, Week 12
Title
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Description
Raw scores of DLCO (% predicted) measured at baseline (time 0), week 6, and week 12 comparing the sildenafil and placebo groups
Time Frame
Baseline, Week 6, Week 12
Title
Change in Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Adjusted Values)
Description
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.
Time Frame
Baseline, 12 week
Title
Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores)
Description
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.
Time Frame
Baseline, 6 week, 12 week
Title
Change in St. George's Respiratory Questionnaire (Total Score) (Adjusted Values)
Description
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.
Time Frame
Baseline, 12 week
Title
St. George's Respiratory Questionnaire (Total Score)
Description
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.)
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in St. George's Respiratory Questionnaire (Symptoms Score) Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
St. George's Respiratory Questionnaire (Symptoms Score)
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in St. George's Respiratory Questionnaire (Activity Score) Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
St. George's Respiratory Questionnaire (Activity Score)
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in St. George's Respiratory Questionnaire (Impacts Score) Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
St. George's Respiratory Questionnaire (Impacts Score)
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in ICECAP-O Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
ICECAP-O
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in EuroQOL Thermometer (Adjusted Value)
Description
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.
Time Frame
Baseline, 12 weeks
Title
EuroQOL Thermometer
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in EuroQOL (EQ-5D) Utility - Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
EuroQOL (EQ-5D) Utility
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in Short Form Health Survey (SF36) General Health - Adjusted Value
Description
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.
Time Frame
Baseline, 12 weeks
Title
Short Form Health Survey (SF36) General Health
Description
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
Time Frame
Baseline, 6 weeks, 12 weeks
Title
Change in SF36 Aggregate Physical (Adjusted Value)
Description
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.
Time Frame
Baseline, 12 weeks
Title
Short Form Health Survey (SF36) Aggregate Physical
Description
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.
Time Frame
Baseline, 6 weeks, 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Hunninghake, MD
Organizational Affiliation
University of Iowa
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kevin Brown, MD
Organizational Affiliation
National Jewish Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rob Kaner, MD
Organizational Affiliation
Weill Medical College at Cornell University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Talmadge King, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joe Lasky, MD
Organizational Affiliation
Tulane University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Loyd, MD
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fernando Martinez, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Imre Noth, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ganesh Raghu, MD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jesse Roman, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jay Ryu, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Zisman, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kevin Anstrom, PhD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Herbert Reynolds, MD
Organizational Affiliation
National Heart, Lung, and Blood Institute (NHLBI)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Lake D Morrison, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama - Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California - San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Tulane University
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98165
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26111071
Citation
Andrade J, Schwarz M, Collard HR, Gentry-Bumpass T, Colby T, Lynch D, Kaner RJ; IPFnet Investigators. The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet): diagnostic and adjudication processes. Chest. 2015 Oct;148(4):1034-1042. doi: 10.1378/chest.14-2889.
Results Reference
derived
PubMed Identifier
25890798
Citation
Durheim MT, Collard HR, Roberts RS, Brown KK, Flaherty KR, King TE Jr, Palmer SM, Raghu G, Snyder LD, Anstrom KJ, Martinez FJ; IPFnet investigators. Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials. Lancet Respir Med. 2015 May;3(5):388-96. doi: 10.1016/S2213-2600(15)00093-4. Epub 2015 Apr 15.
Results Reference
derived
PubMed Identifier
20484178
Citation
Idiopathic Pulmonary Fibrosis Clinical Research Network; Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010 Aug 12;363(7):620-8. doi: 10.1056/NEJMoa1002110. Epub 2010 May 18.
Results Reference
derived

Learn more about this trial

Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis

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