Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 13
- 主要终点
- Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of IPF
- •Diffusing capacity of the lung (DLCO) level less than 35% (adjusted for hemoglobin)
排除标准
- •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
研究组 & 干预措施
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
干预措施: Sildenafil Citrate (Drug)
Placebo / Sildanafil
20 mg of placebo TID for 12 weeks followed by 20 mg of sildenafil citrate TID for an additional 12 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Change in 6-minute Walk Distance From Enrollment to Week 12 (≥ 20% Improvement)
时间窗: 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.
次要结局
- Desaturation During 6-minute Walk Test (6MWT)(Week 12)
- Change in Dyspnea(Measured from enrollment to 12 weeks (phase I))
- Change in Forced Vital Capacity (FVC) Adjusted Values(Baseline, Week 12)
- Forced Vital Capacity (FVC)(Baseline, Week 6, Week 12)
- Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)(Baseline, Week 6, Week 12)
- Change in Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Adjusted Values)(Baseline, 12 week)
- Borg Dyspnea Index (BDI) After 6 Minute Walk Test (Raw Scores)(Baseline, 6 week, 12 week)
- Change in St. George's Respiratory Questionnaire (Total Score) (Adjusted Values)(Baseline, 12 week)
- St. George's Respiratory Questionnaire (Total Score)(Baseline, 6 weeks, 12 weeks)
- Change in St. George's Respiratory Questionnaire (Symptoms Score) Adjusted Value(Baseline, 12 weeks)
- 6-minute Walk Distance (6MWT)(Baseline, 6 week, 12 week)
- Estimated Change From Baseline to 12 Weeks in 6-minute Walk Distance(Baseline, week 12)
- Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Adjusted Values(Baseline, Week 12)
- Change in SF36 Aggregate Physical (Adjusted Value)(Baseline, 12 weeks)
- Short Form Health Survey (SF36) Aggregate Physical(Baseline, 6 weeks, 12 weeks)
- University of California at San Diego (UCSD) Shortness of Breath Questionnaire Total(Baseline, 6 weeks, 12 weeks)
- St. George's Respiratory Questionnaire (Impacts Score)(Baseline, 6 weeks, 12 weeks)
- Change in ICECAP-O Adjusted Value(Baseline, 12 weeks)
- ICECAP-O(Baseline, 6 weeks, 12 weeks)
- Change in EuroQOL Thermometer (Adjusted Value)(Baseline, 12 weeks)
- EuroQOL Thermometer(Baseline, 6 weeks, 12 weeks)
- Change in EuroQOL (EQ-5D) Utility - Adjusted Value(Baseline, 12 weeks)
- St. George's Respiratory Questionnaire (Symptoms Score)(Baseline, 6 weeks, 12 weeks)
- Change in St. George's Respiratory Questionnaire (Activity Score) Adjusted Value(Baseline, 12 weeks)
- St. George's Respiratory Questionnaire (Activity Score)(Baseline, 6 weeks, 12 weeks)
- Change in St. George's Respiratory Questionnaire (Impacts Score) Adjusted Value(Baseline, 12 weeks)
- EuroQOL (EQ-5D) Utility(Baseline, 6 weeks, 12 weeks)
- Change in Short Form Health Survey (SF36) General Health - Adjusted Value(Baseline, 12 weeks)
- Short Form Health Survey (SF36) General Health(Baseline, 6 weeks, 12 weeks)