Losartan Effects on Emphysema Progression
Condition: Emphysema
MeSH terms: Pulmonary Emphysema; Emphysema
Intervention: Losartan; Placebo
Intervention description: 50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated; one capsule per day for two weeks, followed by two capsules per day for 46 weeks
Intervention MeSH terms: Losartan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 220.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: COPD; emphysema; HRCT; losartan

Summary:

      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

      .
    

Eligibility criteria:

        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