Simvastatin Therapy for Moderate and Severe COPD
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: simvastatin; Placebo
Intervention description: 40 mgms of simvastatin daily; Matched placebo pill daily
Intervention MeSH terms: Simvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 885.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; COPD; Exacerbation; Lung function; Cardiovascular; Smoking; Statins; Simvastatin

Summary:

      To determine the effect of daily administration of 40 mgms simvastatin taken for at least 12
      months (range 12-36 months) on the frequency of exacerbations of chronic obstructive lung
      disease (COPD) in patients with moderate to severe COPD who are prone to exacerbations and do
      not have other indications for statin treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects, 40-80 years of age.

          2. Clinical diagnosis of at least moderate COPD as defined by the GOLD criteria:

               1. Postbronchodilator FEV1(forced expiratory volume at one second)/FVC(forced vital
                  capacity) < 70%,

               2. Postbronchodilator FEV1 (forced expiratory volume at one second) < 80% predicted,
                  with or without chronic symptoms (i.e., cough, sputum production).

          3. Cigarette consumption of 10 pack-years or more. Patients may or may not be active
             smokers.

          4. Must meet one or more of the following 4 conditions

               1. Be using supplemental oxygenate

               2. Receiving a course of systemic corticosteroids and/or antibiotics for respiratory
                  problems in the past year,

               3. Visiting an Emergency Department for a COPD exacerbation within the past year, or

               4. Being hospitalized for a COPD (Chronic Obstructive Pulmonary Disease)
                  exacerbation within the past year

          5. Willingness to make return visits and availability by telephone for duration of study.

          6. Free of active coronary disease

          7. Subject with expected life expectancy > 36 months

        Exclusion Criteria:

          1. Patients who:

               1. are on statin drugs.

               2. should be on statins based on established risk stratification using the ATP-III
                  (Adult Treatment Panel) to determine 10 year risk.

          2. Documented history of active coronary heart disease, such as unstable angina, prior
             myocardial infarction, stroke, symptomatic peripheral vascular or carotid artery
             disease, or congestive heart failure within the past 3 months.

          3. A diagnosis of asthma.

          4. The presence of a diagnosis other than COPD that results in the patient being either
             medically unstable, or having a predicted life expectancy < 3 years.

          5. Special patient groups: prisoners, pregnant women, institutionalized patients

          6. Women who are at risk of becoming pregnant during the study (pre-menopausal) and who
             refuse to use acceptable birth control (hormone-based oral or barrier contraceptive)
             for the duration of the study.

          7. Woman using estradiol compounds for contraception. Postmenopausal women on estradiol
             compounds for hormone replacement therapy will be allowed into the trial.

          8. Participants otherwise meeting the inclusion criteria will not be enrolled until they
             are a minimum of four weeks from their most recent acute exacerbation.

          9. A clinical diagnosis of bronchiectasis defined as production of > one-half cup of
             purulent sputum/day.

         10. Participants using niacin, azole antifungals (itraconazole, ketoconazole,
             posaconazole), fibric acid derivatives, erythromycin, clarithromycin, telithromycin,
             diltiazem, amlodipine , ranolazine,HIV protease inhibitors (such as indinavir),
             amiodarone, gemfibrozil, cyclosporine, verapamil, danazol, nefazodone, and red yeast
             rice extracts are excluded

         11. Active liver disease. Active liver disease is defined as ALT (alanine
             aminotransferase), AST (aspartate aminotransferase) as greater than 1.5 times the
             upper limit of normal.

         12. Patients with renal failure defined by serum creatinine greater than 3mg/dl.

         13. Alcoholism. Alcoholism is defined as > 35 drinks per week. A drink is defined as one
             bottle of beer, one 8-ounce glass of wine, or one ounce of hard liquor.

         14. Hypersensitivity to HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase
             inhibitors. Hypersensitivity is defined as an allergic reaction to statin, prior
             history of myopathy, rhabdomyolysis or previous intolerance to statin use.

         15. Participants drinking greater than 4 cups (1qt) of grapefruit juice per day.

         16. Participants drinking greater than 3 cups of green tea per day.

         17. Diabetics will be excluded. Diabetics are defined by:

        1. A CURRENT physician diagnosis of diabetes OR 2. CURRENT use of diabetic meds OR 3.
        Elevated HbA1c > 6.5% 18. The discretion of the Principal Investigator that the potential
        participant will not be a reliable study subject to complete the study requirements.