Simvastatin Therapy for Moderate and Severe COPD

Phase 3

Terminated

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: Placebo; Drug: simvastatin

• Registration Number: NCT01061671
• Lead Sponsor: University of Minnesota

Brief 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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2010-02-02
• Study First Submitted QC: 2010-02-02
• Study First Posted: 2010-02-03
• Study Start: 2010-03
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Results First Submitted: 2015-01-29
• Results First Submitted QC: 2015-03-12
• Results First Posted: 2015-03-26
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-08
• Last Update Posted: 2018-01-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 885

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:

18. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Matched placebo pill daily
simvastatin	simvastatin	40 mgms of simvastatin daily

Primary Outcome Measures

Name	Time	Method
Rates of COPD Exacerbations	up to 37 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (48)

University of Maryland Baltimore; 🇺🇸 Baltimore, Maryland, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Reliant Medical Group; 🇺🇸 Worcester, Massachusetts, United States

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Queen Elizabeth II Health Sciences Center; 🇨🇦 Halifax, Nova Scotia, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Ottawa Civic Hospital; 🇨🇦 Ottawa, Ontario, Canada

Inspiration Research Limited; 🇨🇦 Toronto, Ontario, Canada

LA BioMed at Harbor-UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

University of Illinois Health System; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Temple University Lung Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Pittsburgh VA Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Lovelace Respiratory Research Institute; 🇺🇸 Albuquerque, New Mexico, United States

Western New York Veterans Administration Healthcare System; 🇺🇸 Buffalo, New York, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Royal Columbian Hospital; 🇨🇦 New Westminster, British Columbia, Canada

HealthPartners Research Foundation; 🇺🇸 Minneapolis, Minnesota, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Veteran's Administration Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Utah Health Sciences Center; 🇺🇸 Salt Lake City, Utah, United States

Cincinnati VAMC; 🇺🇸 Cincinnati, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Malcom Randall VA Medical Center; 🇺🇸 Gainesville, Florida, United States

LSU Health; 🇺🇸 New Orleans, Louisiana, United States

Respiratory Specialists; 🇺🇸 Wyomissing, Pennsylvania, United States

St. Luke's Hospital and Health Network; 🇺🇸 Bethlehem, Pennsylvania, United States

Institute for Respiratory and Sleep; 🇺🇸 Langhorne, Pennsylvania, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Surrey Memorial Hospital; 🇨🇦 Surrey, British Columbia, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec (Laval Hospital); 🇨🇦 Quebec, Canada

Lion's Gate Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

St. Boniface Hospital; 🇨🇦 Winnipeg, Manitoba, Canada

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada