Losartan Effects on Emphysema Progression

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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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