Losartan Effects on Emphysema Progression
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 220
- 试验地点
- 28
- 主要终点
- Change in Mean pct950
研究概览
简要总结
A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo
.
详细描述
This is a trial designed to test if a treatment, losartan, may decrease the progression of Chronic Obstructive Pulmonary Disease (COPD). Losartan is an angiotensin receptor blocking agent, commonly used as an antihypertensive agent, which has been shown to alter cardiac remodeling after myocardial infarction and renovascular remodeling in diabetes-mellitus. In this trial participants with mild to severe COPD, with Computed Tomography (CT) evidence of emphysema (5-35% of voxels with < -950 Hounsfield Units), will be randomly assigned to receive 100mg/day of losartan or placebo for 48 weeks. The primary outcome measure will be the rate of progression of emphysema, quantified as the percent of lung voxels with a density less than -950 HU as measured by High Resolution CT (HRCT, from baseline to 48 weeks.
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mild to severe COPD: Ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than or equal to 0.70, FEV1 20-80% of predicted
- •Current or former smoker
- •HRCT scan with 5-35% of voxels with density less than -950 Hounsfield Units (HU)
- •Ability to understand and willingness to sign consent documents
排除标准
- •Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
- •Known intolerance to ACE inhibitor or ARB
- •History of angioedema
- •Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy)
- •Renal insufficiency (GFR <30 mL/min by Cockcroft-Gault calculation)
- •Current regular use of NSAIDs defined as daily use 5 or more days of the week for more than one month
- •Potassium supplementation or serum potassium level of 5.0 milliequivalents (mEq)/dL or higher at V1
- •Current use of a potassium sparing diuretic
- •COPD exacerbation requiring treatment within 6 weeks at V1
- •Chronic systemic corticosteroid use of more than 10mg/day of prednisone
- •Resting SpO2 <89% on 2 L nasal cannula continuous flow; unless at altitude > 4,000 feet, then resting oxygen saturation (SpO2) <89% on 4 L N C continuous flow
- •Untreated arterial hypertension (systolic blood pressure greater than140 mm Hg, diastolic blood pressure greater than 90 mm Hg)
- •Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting
- •Known unilateral or bilateral renal artery stenosis higher than 70%
- •Previous lung resection surgery
- •Evidence of interstitial, occupational or chronic infectious lung disease
- •Changes to chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads)
- •For women of child bearing potential, positive pregnancy test or unwillingness to use two methods of birth control or abstinence for the duration of the study
- •Major chronic illnesses which in the judgment of the study physician would interfere with participation in the study e.g. including but not limited to: cardiac, renal, hepatic (LFTs more than 2.5x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases, uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, non-skin cancer, rheumatic diseases
- •Failure to keep screening appointments or other indicators of non-adherence
- •Inability to be contacted by telephone
- •Intention to leave area within 12 months
研究组 & 干预措施
Losartan
At randomization participants will start with a dose of 50mg (one capsule) once a day for 2 weeks. If this dose is well tolerated and systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 100 mg (2 capsules) once a day for the remaining 46 weeks.
干预措施: Losartan (Drug)
placebo
At randomization participants will start with a dose of one capsule (inactive) once a day for 2 weeks. After two weeks, if systolic BP is >90 mm Hg and diastolic BP is > 60 mm Hg, the dose will be increased to 2 capsules once a day for the remaining 46 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Mean pct950
时间窗: 48 weeks
change in percentage of voxels with density less than -950 Hounsfield Units
次要结局
- Change From Baseline in CAT Score(48 weeks)
- Change From Baseline in SGRQ Score: Symptoms(48 weeks)
- Change From Baseline in SGRQ Score: Activity(48 weeks)
- Change From Baseline in mMRC Dyspnea Scale(48 weeks)
- Change From Baseline in SGRQ Score: Total(48 weeks)
- Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted(48 weeks)
- Change From Baseline in Post-bronchodilator FEV1 Percent Predicted(48 weeks)
- Change in SGRQ Score: Impact(48 weeks)
- Change From Baseline in PROMIS-20a T-score(48 weeks)