STATCOPE: Simvastatin Therapy for Moderate and Severe COPD

• Sponsor: University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01061671
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Canadian Institutes of Health Research (CIHR) (Other), Ottawa Hospital Research Institute (Other)
• Enrollment: 885
• Locations: 51
• Arms: 2
• Duration (Months): 46.1
• Patients Per Site: 17.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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

• Study Type: Interventional
• 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: Mar 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. Time to First COPD Exacerbation [up to 37 months]

2. Change in FEV1 (% Pred) From Baseline to Last Measure [Baseline, last measure at up to 37 months]

3. Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year) [up to 37 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

3. Postbronchodilator FEV1(forced expiratory volume at one second)/FVC(forced vital capacity) < 70%,

4. Postbronchodilator FEV1 (forced expiratory volume at one second) < 80% predicted, with or without chronic symptoms (i.e., cough, sputum production).

5. Cigarette consumption of 10 pack-years or more. Patients may or may not be active smokers.

6. Must meet one or more of the following 4 conditions

7. Be using supplemental oxygenate

8. Receiving a course of systemic corticosteroids and/or antibiotics for respiratory problems in the past year,

9. Visiting an Emergency Department for a COPD exacerbation within the past year, or

10. Being hospitalized for a COPD (Chronic Obstructive Pulmonary Disease) exacerbation within the past year

11. Willingness to make return visits and availability by telephone for duration of study.

12. Free of active coronary disease

13. Subject with expected life expectancy > 36 months

Exclusion Criteria:

1. Patients who:

2. are on statin drugs.

3. should be on statins based on established risk stratification using the ATP-III (Adult Treatment Panel) to determine 10 year risk.

4. 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.

5. A diagnosis of asthma.

6. 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.

7. Special patient groups: prisoners, pregnant women, institutionalized patients

8. 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.

9. Woman using estradiol compounds for contraception. Postmenopausal women on estradiol compounds for hormone replacement therapy will be allowed into the trial.

10. Participants otherwise meeting the inclusion criteria will not be enrolled until they are a minimum of four weeks from their most recent acute exacerbation.

11. A clinical diagnosis of bronchiectasis defined as production of > one-half cup of purulent sputum/day.

12. 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

13. 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.

14. Patients with renal failure defined by serum creatinine greater than 3mg/dl.

15. 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.

16. 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.

17. Participants drinking greater than 4 cups (1qt) of grapefruit juice per day.

18. Participants drinking greater than 3 cups of green tea per day.

19. Diabetics will be excluded. Diabetics are defined by:

20. 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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Veteran's Administration Medical Center	Birmingham	Alabama	United States	35294
3	LA BioMed at Harbor-UCLA Medical Center	Los Angeles	California	United States	90502
4	University of California at San Francisco	San Francisco	California	United States	94143
5	University of Colorado	Aurora	Colorado	United States	80045
6	National Jewish Health	Denver	Colorado	United States	80206
7	Malcom Randall VA Medical Center	Gainesville	Florida	United States	32608
8	Northwestern University	Chicago	Illinois	United States	60611
9	University of Illinois Health System	Chicago	Illinois	United States	60637
10	LSU Health	New Orleans	Louisiana	United States	70112
11	University of Maryland Baltimore	Baltimore	Maryland	United States	21201
12	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
13	Veteran's Administration Medical Center	Boston	Massachusetts	United States	02132
14	Reliant Medical Group	Worcester	Massachusetts	United States	01608
15	Veteran's Administration Medical Center	Ann Arbor	Michigan	United States	48105
16	University of Michigan	Ann Arbor	Michigan	United States	48109
17	Veteran's Administration Medical Center	Minneapolis	Minnesota	United States	55417
18	HealthPartners Research Foundation	Minneapolis	Minnesota	United States	55440
19	Mayo Clinic	Rochester	Minnesota	United States	55905
20	Lovelace Respiratory Research Institute	Albuquerque	New Mexico	United States	87108
21	Western New York Veterans Administration Healthcare System	Buffalo	New York	United States	14125
22	Duke University	Durham	North Carolina	United States	27710
23	Cincinnati VAMC	Cincinnati	Ohio	United States	45220
24	Cleveland Clinic	Cleveland	Ohio	United States	44195
25	Ohio State University	Columbus	Ohio	United States	43221
26	Oregon Health & Science University	Portland	Oregon	United States	97239
27	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania	United States	18015
28	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
29	Institute for Respiratory and Sleep	Langhorne	Pennsylvania	United States	19047
30	Temple University Lung Center	Philadelphia	Pennsylvania	United States	19140
31	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
32	Pittsburgh VA Medical Center	Pittsburgh	Pennsylvania	United States	15240
33	Respiratory Specialists	Wyomissing	Pennsylvania	United States	19601
34	Baylor College of Medicine	Houston	Texas	United States	77030
35	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
36	University of Calgary	Calgary	Alberta	Canada	T2N4Z6
37	University of Alberta	Edmonton	Alberta	Canada	T6G 2C8
38	Royal Columbian Hospital	New Westminster	British Columbia	Canada
39	Surrey Memorial Hospital	Surrey	British Columbia	Canada	V3V1N1
40	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z1M9
41	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
42	Lion's Gate Hospital	Vancouver	British Columbia	Canada	V7M2H9
43	St. Boniface Hospital	Winnipeg	Manitoba	Canada	R2H2A6
44	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 3A7
45	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
46	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
47	Ottawa Civic Hospital	Ottawa	Ontario	Canada	K1Y4E9
48	Inspiration Research Limited	Toronto	Ontario	Canada	M5T 3A9
49	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
50	Royal University Hospital	Saskatoon	Saskatchewan	Canada	S7N 0W8
51	Institut Universitaire de Cardiologie et de Pneumologie de Québec (Laval Hospital)	Quebec		Canada	G1V 4G5

Sponsors and Collaborators

• University of Minnesota
• 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, 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01061671
• Other Study ID Numbers: 689; U10HL074424
• First Posted: Feb 3, 2010
• Last Update Posted: Jan 2, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by University of Minnesota: Chronic Obstructive Pulmonary Disease; COPD; Exacerbation; Lung function; Cardiovascular; Smoking; Statins; Simvastatin
• Additional relevant MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive; Simvastatin

Study Results

Participant Flow

Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Period Title: Overall Study
STARTED	433	452
COMPLETED	386	397
NOT COMPLETED	47	55

Baseline Characteristics

Arm/Group Title	Simvastatin	Placebo	Total
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily	Total of all reporting groups
Overall Participants	433	452	885
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (8.5)	62.3 (8.4)	62.2 (8.4)
Sex: Female, Male (Count of Participants)
Female	184 42.5%	203 44.9%	387 43.7%
Male	249 57.5%	249 55.1%	498 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 0.9%	7 1.5%	11 1.2%
Not Hispanic or Latino	429 99.1%	445 98.5%	874 98.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.5%	3 0.7%	5 0.6%
Asian	2 0.5%	0 0%	2 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.1%
Black or African American	99 22.9%	91 20.1%	190 21.5%
White	328 75.8%	346 76.5%	674 76.2%
More than one race	2 0.5%	11 2.4%	13 1.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	362 83.6%	376 83.2%	738 83.4%
Canada	71 16.4%	76 16.8%	147 16.6%
Smoking History (Pack Years) (Pack Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Pack Years]	50.0 (26.1)	51.2 (28.7)	50.6 (27.4)
Post-bronchodilator FEV1 (forced expiratory volume at one second) (liters (L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters (L)]	1.19 (0.58)	1.19 (0.56)	1.19 (0.57)
FEV1/FVC (forced expiratory volume at one second/forced vital capacity) (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	0.44 (0.13)	0.44 (0.13)	0.44 (0.13)
FEV1 (% Predicted) (percent predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted]	41.5 (17.8)	41.6 (17.6)	41.6 (17.7)
Acute COPD Exacerbation requiring Hospitalization or ED visit within previous 12 mo (participants) [Number]
Yes	216 49.9%	238 52.7%	454 51.3%
No	217 50.1%	214 47.3%	431 48.7%
Systemic glucocorticoid or antibiotic use within previous 12 mo (participants) [Number]
Yes	367 84.8%	382 84.5%	749 84.6%
No	66 15.2%	70 15.5%	136 15.4%
Use of supplemental oxygen within previous 12 mo (participants) [Number]
Yes	198 45.7%	222 49.1%	420 47.5%
No	235 54.3%	230 50.9%	465 52.5%

Outcome Measures

1. Primary Outcome

Title	Rates of COPD Exacerbations
Time Frame	up to 37 months

Outcome Measure Data

Analysis Population Description

Analysis excludes participants without any follow-up data.

Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Measure Participants	430	447
Mean (Standard Deviation) [exacerbations/person-year]	1.36 (1.61)	1.39 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	negative binomial regression
	Comments	Adjustments of confidence intervals for between-participant variation (overdispersion).

2. Secondary Outcome

Title	Time to First COPD Exacerbation
Time Frame	up to 37 months

Outcome Measure Data

Analysis Population Description

Analysis excludes participants without any follow-up data.

Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Measure Participants	430	447
Median (95% Confidence Interval) [Days to the first exacerbation]	223	231

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Change in FEV1 (% Pred) From Baseline to Last Measure
Time Frame	Baseline, last measure at up to 37 months

Outcome Measure Data

Analysis Population Description

Analysis excludes participants without any follow-up data.

Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Measure Participants	356	356
Median (90% Confidence Interval) [percent predicted]	-0.86	-1.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.1461
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year)
Time Frame	up to 37 months

Outcome Measure Data

Analysis Population Description

Analysis excludes participants without any follow-up data.

Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Measure Participants	430	447
Mean (95% Confidence Interval) [events per patient year]	0.31	0.31

Adverse Events

Time Frame	Up to 37 months
Arm/Group Title	Simvastatin		Placebo
Arm/Group Description	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily		Matched placebo pill daily Placebo: Matched placebo pill daily
All Cause Mortality
	Simvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Simvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	178/433 (41.1%)		190/452 (42%)
Blood and lymphatic system disorders
Cavernous Hemangioma	0/433 (0%)	0	1/452 (0.2%)	2
Cardiac disorders
Rheumatic Heart Disease	1/433 (0.2%)	1	0/452 (0%)	0
Ischemic Heart Disease	4/433 (0.9%)	4	6/452 (1.3%)	6
Pulmonary Circulation disorders	4/433 (0.9%)	5	6/452 (1.3%)	6
Pericarditis	1/433 (0.2%)	1	0/452 (0%)	0
Cardiomyopathy	2/433 (0.5%)	2	0/452 (0%)	0
Cardiac Dysrhythmias	7/433 (1.6%)	7	4/452 (0.9%)	5
Heart Failure	4/433 (0.9%)	6	5/452 (1.1%)	7
Tachycardia	1/433 (0.2%)	1	0/452 (0%)	0
Eye disorders
Orbital cellulitis	0/433 (0%)	0	1/452 (0.2%)	1
Gastrointestinal disorders
Esophagus and stomach disorders	1/433 (0.2%)	1	5/452 (1.1%)	5
Appendicitis	1/433 (0.2%)	1	0/452 (0%)	0
Abdominal Hernia	2/433 (0.5%)	2	2/452 (0.4%)	2
Enteritis	3/433 (0.7%)	3	0/452 (0%)	0
Other Intestinal disorders	7/433 (1.6%)	9	5/452 (1.1%)	5
Other Digestive Disorders	11/433 (2.5%)	14	7/452 (1.5%)	8
Nissen Fundoplication	0/433 (0%)	0	1/452 (0.2%)	1
Ill defined digestive symptoms	1/433 (0.2%)	1	2/452 (0.4%)	2
General disorders
Syncope	5/433 (1.2%)	5	1/452 (0.2%)	1
Dizziness	2/433 (0.5%)	2	0/452 (0%)	0
Severe Headaches	1/433 (0.2%)	1	0/452 (0%)	0
Ill defined abdominal pain	2/433 (0.5%)	2	3/452 (0.7%)	4
Sudden death of unknown cause	4/433 (0.9%)	4	4/452 (0.9%)	4
Complications of surgical and medical care	4/433 (0.9%)	4	2/452 (0.4%)	2
Respiratory Arrest	2/433 (0.5%)	2	1/452 (0.2%)	1
Abnormal Gait	1/433 (0.2%)	1	0/452 (0%)	0
Epistaxis	1/433 (0.2%)	1	0/452 (0%)	0
Sepsis	1/433 (0.2%)	1	4/452 (0.9%)	4
Fatigue	0/433 (0%)	0	1/452 (0.2%)	1
Infections and infestations
Bacterial Infection	0/433 (0%)	0	1/452 (0.2%)	1
Viral Infection	1/433 (0.2%)	1	0/452 (0%)	0
Other Infection	0/433 (0%)	0	1/452 (0.2%)	1
Injury, poisoning and procedural complications
Fractures	7/433 (1.6%)	7	4/452 (0.9%)	4
Sprain	1/433 (0.2%)	1	1/452 (0.2%)	1
Intracranial injury	1/433 (0.2%)	1	0/452 (0%)	0
Internal Injury	1/433 (0.2%)	2	1/452 (0.2%)	1
Contusion	1/433 (0.2%)	1	0/452 (0%)	0
Trauma from motorcycle accident	1/433 (0.2%)	1	0/452 (0%)	0
Poisoning	1/433 (0.2%)	1	1/452 (0.2%)	1
Concussion	0/433 (0%)	0	1/452 (0.2%)	1
Metabolism and nutrition disorders
Metabolic disorders	5/433 (1.2%)	6	5/452 (1.1%)	5
Musculoskeletal and connective tissue disorders
Arthropathy	1/433 (0.2%)	1	5/452 (1.1%)	6
Dorsopathy	4/433 (0.9%)	4	3/452 (0.7%)	3
Rheumatism	3/433 (0.7%)	3	1/452 (0.2%)	1
Osteopathy	2/433 (0.5%)	2	1/452 (0.2%)	1
Spondylolisthesis	1/433 (0.2%)	1	0/452 (0%)	0
Degenerative Disc Disease	1/433 (0.2%)	1	0/452 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer	0/433 (0%)	0	1/452 (0.2%)	1
Liver Cancer	0/433 (0%)	0	1/452 (0.2%)	2
Respiratory Cancer	9/433 (2.1%)	12	10/452 (2.2%)	14
Bone Neoplasm	1/433 (0.2%)	1	4/452 (0.9%)	4
Genitourinary Neoplasm	4/433 (0.9%)	5	5/452 (1.1%)	7
Squamous Cell Carcinoma	0/433 (0%)	0	1/452 (0.2%)	1
Lymphatic Neoplasm	0/433 (0%)	0	1/452 (0.2%)	1
Neuroendocrine Neoplasm	1/433 (0.2%)	1	1/452 (0.2%)	1
Nervous system disorders
Central Nervous System disorders	1/433 (0.2%)	1	0/452 (0%)	0
Pain	0/433 (0%)	0	2/452 (0.4%)	2
Seizure	0/433 (0%)	0	1/452 (0.2%)	1
Psychiatric disorders
Mental Disorder	3/433 (0.7%)	4	5/452 (1.1%)	6
Altered Mental Status	0/433 (0%)	0	1/452 (0.2%)	1
Renal and urinary disorders
Nephrotic disorders	2/433 (0.5%)	2	0/452 (0%)	0
Other Urinary Disorder	5/433 (1.2%)	5	5/452 (1.1%)	5
Disorders of the Male Genitourinary System	0/433 (0%)	0	2/452 (0.4%)	3
Disorders of the Female Genitourinary System	1/433 (0.2%)	1	1/452 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Infection	1/433 (0.2%)	3	1/452 (0.2%)	1
Pneumonia	34/433 (7.9%)	40	27/452 (6%)	32
Influenza	5/433 (1.2%)	5	6/452 (1.3%)	9
Bronchitis	0/433 (0%)	0	1/452 (0.2%)	2
Emphysema	3/433 (0.7%)	3	1/452 (0.2%)	1
Pneumoconioses	0/433 (0%)	0	1/452 (0.2%)	1
COPD Exacerbation	96/433 (22.2%)	155	97/452 (21.5%)	187
COPD other	9/433 (2.1%)	9	10/452 (2.2%)	15
Other Respiratory	12/433 (2.8%)	14	13/452 (2.9%)	20
Ill Defined Respiratory events	10/433 (2.3%)	11	13/452 (2.9%)	15
Hypoxemia	0/433 (0%)	0	2/452 (0.4%)	2
Skin and subcutaneous tissue disorders
Skin Infection	2/433 (0.5%)	2	3/452 (0.7%)	4
Cellulitis	1/433 (0.2%)	1	0/452 (0%)	0
Vascular disorders
Cerebrovascular	1/433 (0.2%)	1	6/452 (1.3%)	6
Artery disorder	2/433 (0.5%)	2	2/452 (0.4%)	3
Vein disorder	4/433 (0.9%)	4	3/452 (0.7%)	4
Other (Not Including Serious) Adverse Events
	Simvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	316/433 (73%)		329/452 (72.8%)
General disorders
Headache	16/433 (3.7%)	20	23/452 (5.1%)	27
Musculoskeletal and connective tissue disorders
Arthropathies	25/433 (5.8%)	38	32/452 (7.1%)	43
Dorsopathies	27/433 (6.2%)	35	27/452 (6%)	32
Rheumatism	67/433 (15.5%)	89	54/452 (11.9%)	73
Renal and urinary disorders
Urinary Infection	26/433 (6%)	56	23/452 (5.1%)	30
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Infection	109/433 (25.2%)	159	107/452 (23.7%)	166
Pneumonia	22/433 (5.1%)	25	17/452 (3.8%)	19
COPD Exacerbation	232/433 (53.6%)	642	244/452 (54%)	649
Other COPD Related Symptoms	41/433 (9.5%)	79	43/452 (9.5%)	80
Dyspnea	65/433 (15%)	94	59/452 (13.1%)	90

Limitations/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.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.