Simvastatin Therapy for Moderate and Severe COPD

NCT ID: NCT01061671

Last Updated: 2018-01-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 885 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2014-01-31

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

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

simvastatin

40 mgms of simvastatin daily

Group Type: ACTIVE_COMPARATOR

simvastatin

Intervention Type: DRUG

40 mgms of simvastatin daily

placebo

Matched placebo pill daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matched placebo pill daily

Interventions

simvastatin

40 mgms of simvastatin daily

Intervention Type: DRUG

Placebo

Matched placebo pill daily

Intervention Type: DRUG

Other Intervention Names

Zocor; sugar pill

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

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.

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John E Connett, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota (Data Coordinating Center)

Steven M Scharf, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Mark Dransfield, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

George Washko, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital Boston

Richard K Albert, MD

Role: PRINCIPAL_INVESTIGATOR

Denver Health Medical Center

Richard Casaburi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Harbor-UCLA Research & Education Institute

Dennis E Niewoehner, MD

Role: PRINCIPAL_INVESTIGATOR

Minnesota Veterans Affairs Medical Center

Gerard J Criner, MD

Role: PRINCIPAL_INVESTIGATOR

Temple University Philadelphia

Frank Sciurba, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Stephen C Lazarus, MD

Role: PRINCIPAL_INVESTIGATOR

University of California at San Francisco

Fernando J Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Don Sin, M.D.

Role: PRINCIPAL_INVESTIGATOR

St. Paul's Hospital

Shawn Aaron, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Veteran's Administration Medical Center

Birmingham, Alabama, United States

LA BioMed at Harbor-UCLA Medical Center

Los Angeles, California, United States

University of California at San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

National Jewish Health

Denver, Colorado, United States

Malcom Randall VA Medical Center

Gainesville, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Illinois Health System

Chicago, Illinois, United States

LSU Health

New Orleans, Louisiana, United States

University of Maryland Baltimore

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Veteran's Administration Medical Center

Boston, Massachusetts, United States

Reliant Medical Group

Worcester, Massachusetts, United States

Veteran's Administration Medical Center

Ann Arbor, Michigan, United States

University of Michigan

Ann Arbor, Michigan, United States

Veteran's Administration Medical Center

Minneapolis, Minnesota, United States

HealthPartners Research Foundation

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Lovelace Respiratory Research Institute

Albuquerque, New Mexico, United States

Western New York Veterans Administration Healthcare System

Buffalo, New York, United States

Duke University

Durham, North Carolina, United States

Cincinnati VAMC

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

St. Luke's Hospital and Health Network

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Institute for Respiratory and Sleep

Langhorne, Pennsylvania, United States

Temple University Lung Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Pittsburgh VA Medical Center

Pittsburgh, Pennsylvania, United States

Respiratory Specialists

Wyomissing, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

University of Calgary

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Surrey Memorial Hospital

Surrey, British Columbia, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Lion's Gate Hospital

Vancouver, British Columbia, Canada

St. Boniface Hospital

Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Ottawa Civic Hospital

Ottawa, Ontario, Canada

Inspiration Research Limited

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec (Laval Hospital)

Québec, , Canada

Countries

United States; Canada

References

Camac ER, Voelker H, Criner GJ; COPD Clinical Research Network and the Canadian Institutes of Health Research. Impact of COPD exacerbations leading to hospitalization on general and disease-specific quality of life. Respir Med. 2021 Sep;186:106526. doi: 10.1016/j.rmed.2021.106526. Epub 2021 Jun 29.

Reference Type: DERIVED

PMID: 34229290 (View on PubMed)

Rao AK, Del Carpio-Cano F, Janapati S, Zhao H, Voelker H, Lu X, Criner G; NIH COPD Clinical Research Network, the Canadian Institute of Health Research Investigators. Effects of simvastatin on tissue factor pathway of blood coagulation in STATCOPE (Simvastatin in the prevention of COPD exacerbations) trial. J Thromb Haemost. 2021 Jul;19(7):1709-1717. doi: 10.1111/jth.15282. Epub 2021 Apr 12.

Reference Type: DERIVED

PMID: 33638931 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29444682 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29065885 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24836125 (View on PubMed)

Other Identifiers

U10HL074424

Identifier Type: NIH

Identifier Source: secondary_id

View Link

689

Identifier Type: -

Identifier Source: org_study_id