Simvastatin Therapy for Moderate and Severe COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

— STATCOPE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01061671
• Other study ID #: 689
• Secondary ID: U10HL074424
• Status: Terminated
• Phase: Phase 3
• First received: February 2, 2010
• Last updated: December 8, 2017
• Start date: March 2010
• Est. completion date: January 2014

Study information

• Verified date: December 2017
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 885
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• simvastatin
40 mgms of simvastatin daily
• Placebo
Matched placebo pill daily

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Ottawa Civic Hospital	Ottawa	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec (Laval Hospital)	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	Inspiration Research Limited	Toronto	Ontario
Canada	Lion's Gate Hospital	Vancouver	British Columbia
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	St. Boniface Hospital	Winnipeg	Manitoba
United States	Lovelace Respiratory Research Institute	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Veteran's Administration Medical Center	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland Baltimore	Baltimore	Maryland
United States	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Veteran's Administration Medical Center	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Veteran's Administration Medical Center	Boston	Massachusetts
United States	Western New York Veterans Administration Healthcare System	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois Health System	Chicago	Illinois
United States	Cincinnati VAMC	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	National Jewish Health	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	Malcom Randall VA Medical Center	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Institute for Respiratory and Sleep	Langhorne	Pennsylvania
United States	LA BioMed at Harbor-UCLA Medical Center	Los Angeles	California
United States	HealthPartners Research Foundation	Minneapolis	Minnesota
United States	Veteran's Administration Medical Center	Minneapolis	Minnesota
United States	LSU Health	New Orleans	Louisiana
United States	Temple University Lung Center	Philadelphia	Pennsylvania
United States	Pittsburgh VA Medical Center	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	University of California at San Francisco	San Francisco	California
United States	Reliant Medical Group	Worcester	Massachusetts
United States	Respiratory Specialists	Wyomissing	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI), Ottawa Hospital Research Institute

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of COPD Exacerbations		up to 37 months
Secondary	Time to First COPD Exacerbation		up to 37 months
Secondary	Change in FEV1 (% Pred) From Baseline to Last Measure		Baseline, last measure at up to 37 months
Secondary	Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year)		up to 37 months