Simvastatin Therapy for Moderate and Severe COPD

NCT01061671 | Terminated Phase 3 Results DMC

• 2 other identifiers: 689U10HL074424
• Study Type: interventional
• Target: 885
• Locations: 2 countries
• Sites: 51

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rates of COPD Exacerbations

  up to 37 months

Secondary Outcomes (3)

• 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

Study Arms (2)

simvastatin

ACTIVE COMPARATOR

40 mgms of simvastatin daily

Drug: simvastatin

placebo

PLACEBO COMPARATOR

Matched placebo pill daily

Drug: Placebo

Interventions

simvastatin DRUG

40 mgms of simvastatin daily

Also known as: Zocor

simvastatin

Placebo DRUG

Matched placebo pill daily

Also known as: sugar pill

placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Minnesota: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Ottawa Hospital Research Institute: collaborator

Study Sites (51)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Veteran's Administration Medical Center

Birmingham, Alabama, 35294, United States

Location

LA BioMed at Harbor-UCLA Medical Center

Los Angeles, California, 90502, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Malcom Randall VA Medical Center

Gainesville, Florida, 32608, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois Health System

Chicago, Illinois, 60637, United States

Location

LSU Health

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Veteran's Administration Medical Center

Boston, Massachusetts, 02132, United States

Location

Reliant Medical Group

Worcester, Massachusetts, 01608, United States

Location

Veteran's Administration Medical Center

Ann Arbor, Michigan, 48105, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Veteran's Administration Medical Center

Minneapolis, Minnesota, 55417, United States

Location

HealthPartners Research Foundation

Minneapolis, Minnesota, 55440, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Lovelace Respiratory Research Institute

Albuquerque, New Mexico, 87108, United States

Location

Western New York Veterans Administration Healthcare System

Buffalo, New York, 14125, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati VAMC

Cincinnati, Ohio, 45220, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital and Health Network

Bethlehem, Pennsylvania, 18015, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Institute for Respiratory and Sleep

Langhorne, Pennsylvania, 19047, United States

Location

Temple University Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Pittsburgh VA Medical Center

Pittsburgh, Pennsylvania, 15240, United States

Location

Respiratory Specialists

Wyomissing, Pennsylvania, 19601, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

University of Calgary

Calgary, Alberta, T2N4Z6, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

Surrey Memorial Hospital

Surrey, British Columbia, V3V1N1, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z1M9, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Lion's Gate Hospital

Vancouver, British Columbia, V7M2H9, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H2A6, Canada

Location

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H 3A7, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Ottawa Civic Hospital

Ottawa, Ontario, K1Y4E9, Canada

Location

Inspiration Research Limited

Toronto, Ontario, M5T 3A9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

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

Québec, G1V 4G5, Canada

Location

Related Publications (5)

• 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.

  PMID: 34229290 DERIVED

• 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.

  PMID: 33638931 DERIVED

• 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.

  PMID: 29444682 DERIVED

• 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.

  PMID: 29065885 DERIVED

• 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.

  PMID: 24836125 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking

Interventions

Simvastatin; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

Early termination by the Data and Safety Monitoring Board due to futility in respect to a treatment effect. The original study population goal was 1200 and the study was terminated at 885 participants.

Results Point of Contact

• Title: Sarah Lindberg
• Organization: University of Minnesota

sharnden@ccbr.umn.edu

612-626-9011

Study Officials

• John E Connett, PhD

  University of Minnesota (Data Coordinating Center)

  PRINCIPAL INVESTIGATOR

• Steven M Scharf, MD, PhD

  University of Maryland, Baltimore

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2010
• First Posted: February 3, 2010
• Study Start: March 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 2, 2018
• Results First Posted: March 26, 2015

Record last verified: 2017-12

Locations

US (35); CA (16)