Simvastatin Therapy for Moderate and Severe COPD

Study Overview
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Brief Summary
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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.

Detailed Description
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COPD exacerbation is a common complication that significantly contributes to the high morbidity, mortality and costs associated with COPD. COPD exacerbations are associated with heightened lung inflammation that may have systemic implications (e.g., peripheral muscle weakness, cognitive impairment, depression, stroke, acute coronary syndrome, and atherosclerosis). Statins are potent agents that significantly reduce vascular events in patients with increased risks due to prior cardiac or cerebral vascular events and elevated lipid profiles. Statins have pleiotropic effects that extend well beyond their lipid lowering effects and may be potent anti-inflammatory agents. Retrospective data conducted in COPD patients indicate that statin use is associated with markedly decreased rates of COPD hospitalization and stabilization of lung function. Decreases in mortality in COPD due to complications of flu-like illnesses and deaths due to cardiovascular events have also been reported. Inflammatory biomarkers (C-reactive protein and interleukin- 6) are reported to be elevated in moderate to severe COPD patients who are prone to exacerbations. Inflammatory biomarkers (C-reactive protein and interleukin- 6) are reported to be reduced by statin therapy in patients with hyperlipidemia and cardiovascular diseases. Treatments that can effectively lessen the prevalence and severity of COPD exacerbations are desperately needed

Official Title
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Prospective Randomized Placebo-Controlled Trial of SimvaSTATin in the Prevention of COPD Exacerbations (STATCOPE)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, 40-80 years of age. Clinical diagnosis of at least moderate COPD as defined by the GOLD criteria: Postbronchodilator FEV1(forced expiratory volume at one second)/FVC(forced vital capacity) < 70%, Postbronchodilator FEV1 (forced expiratory volume at one second) < 80% predicted, with or without chronic symptoms (i.e., cough, sputum production). Cigarette consumption of 10 pack-years or more. Patients may or may not be active smokers. Must meet one or more of the following 4 conditions Be using supplemental oxygenate Receiving a course of systemic corticosteroids and/or antibiotics for respiratory problems in the past year, Visiting an Emergency Department for a COPD exacerbation within the past year, or Being hospitalized for a COPD (Chronic Obstructive Pulmonary Disease) exacerbation within the past year Willingness to make return visits and availability by telephone for duration of study. Free of active coronary disease Subject with expected life expectancy > 36 months Exclusion Criteria: Patients who: are on statin drugs. should be on statins based on established risk stratification using the ATP-III (Adult Treatment Panel) to determine 10 year risk. 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. A diagnosis of asthma. 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. Special patient groups: prisoners, pregnant women, institutionalized patients 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. Woman using estradiol compounds for contraception. Postmenopausal women on estradiol compounds for hormone replacement therapy will be allowed into the trial. Participants otherwise meeting the inclusion criteria will not be enrolled until they are a minimum of four weeks from their most recent acute exacerbation. A clinical diagnosis of bronchiectasis defined as production of > one-half cup of purulent sputum/day. 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 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. Patients with renal failure defined by serum creatinine greater than 3mg/dl. 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. 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. Participants drinking greater than 4 cups (1qt) of grapefruit juice per day. Participants drinking greater than 3 cups of green tea per day. 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: simvastatin<br>40 mgms of simvastatin daily | Drug: simvastatin<br>* 40 mgms of simvastatin daily<br>* Other names: Zocor;|
| Placebo Comparator: placebo<br>Matched placebo pill daily | Drug: Placebo<br>* Matched placebo pill daily<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of COPD Exacerbations |  | up to 37 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First COPD Exacerbation |  | up to 37 months | 
| Change in FEV1 (% Pred) From Baseline to Last Measure |  | Baseline, last measure at up to 37 months | 
| Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year) |  | up to 37 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Simvastatin, Chronic Obstructive Pulmonary Disease, Exacerbation, Lung function, Cardiovascular, Smoking, Statins