Simvastatin Therapy for Moderate and Severe COPD (STATCOPE)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: simvastatin; Drug: Placebo	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	885 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Prospective Randomized Placebo-Controlled Trial of SimvaSTATin in the Prevention of COPD Exacerbations (STATCOPE)
Study Start Date :	March 2010
Actual Primary Completion Date :	January 2014
Actual Study Completion Date :	January 2014

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: simvastatin; 40 mgms of simvastatin daily	Drug: simvastatin; 40 mgms of simvastatin daily; Other Name: Zocor
Placebo Comparator: placebo; Matched placebo pill daily	Drug: Placebo; Matched placebo pill daily; Other Name: sugar pill

Outcome Measures

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Primary Outcome Measures :

1. Rates of COPD Exacerbations [ Time Frame: up to 37 months ]

Secondary Outcome Measures :

1. Time to First COPD Exacerbation [ Time Frame: up to 37 months ]
2. Change in FEV1 (% Pred) From Baseline to Last Measure [ Time Frame: Baseline, last measure at up to 37 months ]
3. Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year) [ Time Frame: up to 37 months ]

Eligibility Criteria

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Ages Eligible for Study:	40 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 51 Study Locations

Sponsors and Collaborators

University of Minnesota - Clinical and Translational Science Institute

National Heart, Lung, and Blood Institute (NHLBI)

Canadian Institutes of Health Research (CIHR)

Ottawa Hospital Research Institute

Investigators

Principal Investigator:	John E Connett, PhD	University of Minnesota (Data Coordinating Center)
Principal Investigator:	Steven M Scharf, MD, PhD	University of Maryland
Principal Investigator:	Mark Dransfield, MD	University of Alabama at Birmingham
Principal Investigator:	George Washko, MD	Brigham and Women's Hospital Boston
Principal Investigator:	Richard K Albert, MD	Denver Health Medical Center
Principal Investigator:	Richard Casaburi, MD, PhD	Harbor-UCLA Research & Education Institute
Principal Investigator:	Dennis E Niewoehner, MD	Minnesota Veterans Affairs Medical Center
Principal Investigator:	Gerard J Criner, MD	Temple University Philadelphia
Principal Investigator:	Frank Sciurba, MD	University of Pittsburgh
Principal Investigator:	Stephen C Lazarus, MD	University of California at San Francisco
Principal Investigator:	Fernando J Martinez, MD	University of Michigan
Principal Investigator:	Don Sin, M.D.	St. Paul's Hospital
Principal Investigator:	Shawn Aaron, M.D.	The Ottawa Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Paul Man SF, Aaron SD, Reed RM, Sin DD; Canadian Respiratory Research Network (CRRN). Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018 Feb 14;19(1):30. doi: 10.1186/s12931-018-0733-z.

Brown KE, Sin DD, Voelker H, Connett JE, Niewoehner DE, Kunisaki KM; COPD Clinical Research Network. Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations. Respir Res. 2017 Oct 24;18(1):179. doi: 10.1186/s12931-017-0664-0.

Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey WC, Casaburi R, Cooper JA Jr, Curtis JL, Dransfield MT, Han MK, Make B, Marchetti N, Martinez FJ, Niewoehner DE, Scanlon PD, Sciurba FC, Scharf SM, Sin DD, Voelker H, Washko GR, Woodruff PG, Lazarus SC; COPD Clinical Research Network; Canadian Institutes of Health Research. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014 Jun 5;370(23):2201-10. doi: 10.1056/NEJMoa1403086. Epub 2014 May 18.

Responsible Party:	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT01061671 History of Changes
Other Study ID Numbers:	689; U10HL074424 ( U.S. NIH Grant/Contract )
First Posted:	February 3, 2010
Results First Posted:	March 26, 2015
Last Update Posted:	January 2, 2018
Last Verified:	December 2017

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

Chronic Obstructive Pulmonary Disease; COPD; Exacerbation; Lung function	Cardiovascular; Smoking; Statins; Simvastatin

Additional relevant MeSH terms:

Lung Diseases; Chronic Disease; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Lung Diseases, Obstructive; Simvastatin	Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors