Simvastatin Therapy for Moderate and Severe COPD (STATCOPE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01061671

Recruitment Status : Terminated (Futility)

First Posted : February 3, 2010

Results First Posted : March 26, 2015

Last Update Posted : January 2, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

National Heart, Lung, and Blood Institute (NHLBI)

Canadian Institutes of Health Research (CIHR)

Ottawa Hospital Research Institute

Information provided by (Responsible Party):

University of Minnesota

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Pulmonary Disease, Chronic Obstructive
Interventions	Drug: simvastatin Drug: Placebo
Enrollment	885

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Simvastatin	Placebo
Arm/Group Description	40 mgms of simvastatin daily ...	Matched placebo pill daily ...
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
Reason Not Completed
Withdrawal by Subject	16	20
Lost to Follow-up	3	5
Death	28	30

Baseline Characteristics

Arm/Group Title		Simvastatin	Placebo	Total
Arm/Group Description		40 mgms of simvastatin daily ...	Matched placebo pill daily ...	Total of all reporting groups
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 Number of Baseline Participants		433	452	885
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	433 participants	452 participants	885 participants
		62.2 (8.5)	62.3 (8.4)	62.2 (8.4)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	433 participants	452 participants	885 participants
	Female	184 42.5%	203 44.9%	387 43.7%
	Male	249 57.5%	249 55.1%	498 56.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	433 participants	452 participants	885 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%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	433 participants	452 participants	885 participants
	American Indian or Alaska Native	2 0.5%	3 0.7%	5 0.6%
	Asian	2 0.5%	0 0.0%	2 0.2%
	Native Hawaiian or Other Pacific Islander	0 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%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	433 participants	452 participants	885 participants
United States		362	376	738
Canada		71	76	147
Smoking History (Pack Years) Mean (Standard Deviation) Unit of measure: Pack Years
	Number Analyzed	433 participants	452 participants	885 participants
		50.0 (26.1)	51.2 (28.7)	50.6 (27.4)
Post-bronchodilator FEV1 (forced expiratory volume at one second) Mean (Standard Deviation) Unit of measure: Liters (L)
	Number Analyzed	433 participants	452 participants	885 participants
		1.19 (0.58)	1.19 (0.56)	1.19 (0.57)
FEV1/FVC (forced expiratory volume at one second/forced vital capacity) Mean (Standard Deviation) Unit of measure: Ratio
	Number Analyzed	433 participants	452 participants	885 participants
		0.44 (0.13)	0.44 (0.13)	0.44 (0.13)
FEV1 (% Predicted) Mean (Standard Deviation) Unit of measure: Percent predicted
	Number Analyzed	433 participants	452 participants	885 participants
		41.5 (17.8)	41.6 (17.6)	41.6 (17.7)
Acute COPD Exacerbation requiring Hospitalization or ED visit within previous 12 mo ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	433 participants	452 participants	885 participants
Yes		216	238	454
No		217	214	431
		[1] Measure Description: Acute COPD (Chronic Obstructive Pulmonary Disease) Exacerbation requiring Hospitalization or Emergency Department visit within previous 12 months
Systemic glucocorticoid or antibiotic use within previous 12 mo Measure Type: Number Unit of measure: Participants	Number Analyzed	433 participants	452 participants	885 participants
Yes		367	382	749
No		66	70	136
Use of supplemental oxygen within previous 12 mo Measure Type: Number Unit of measure: Participants	Number Analyzed	433 participants	452 participants	885 participants
Yes		198	222	420
No		235	230	465

Outcome Measures

1.Primary Outcome


Title	Rates of COPD Exacerbations
Description	[Not Specified]
Description	[Not Specified]
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 ...	Matched placebo pill daily ...
Arm/Group Description:	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Overall Number of Participants Analyzed	430	447
Mean (Standard Deviation) Unit of Measure: exacerbations/person-year
	1.36 (1.61)	1.39 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.54
	Comments	[Not Specified]
	Method	negative binomial regression
	Comments	Adjustments of confidence intervals for between-participant variation (overdispersion).

2.Secondary Outcome


Title	Time to First COPD Exacerbation
Description	[Not Specified]
Description	[Not Specified]
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 ...	Matched placebo pill daily ...
Arm/Group Description:	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Overall Number of Participants Analyzed	430	447
Median (95% Confidence Interval) Unit of Measure: Days to the first exacerbation
	223 (195 to 275)	231 (193 to 303)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.34
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

3.Secondary Outcome


Title	Change in FEV1 (% Pred) From Baseline to Last Measure
Description	[Not Specified]
Description	[Not Specified]
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 ...	Matched placebo pill daily ...
Arm/Group Description:	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Overall Number of Participants Analyzed	356	356
Median (90% Confidence Interval) Unit of Measure: percent predicted
	-0.86 (-11.04 to 8.67)	-1.81 (-10.62 to 7.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simvastatin, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.1461
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

4.Secondary Outcome


Title	Acute Exacerbation COPD Hospitalization Rates (Events/Patient Year)
Description	[Not Specified]
Description	[Not Specified]
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 ...	Matched placebo pill daily ...
Arm/Group Description:	40 mgms of simvastatin daily Simvastatin: 40 mgms of simvastatin daily	Matched placebo pill daily Placebo: Matched placebo pill daily
Overall Number of Participants Analyzed	430	447
Mean (95% Confidence Interval) Unit of Measure: events per patient year
	0.31 (0.24 to 0.38)	0.31 (0.23 to 0.38)

Adverse Events

Time Frame	Up to 37 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Simvastatin		Placebo
Arm/Group Description	40 mgms of simvastatin daily ...		Matched placebo pill daily ...
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 (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Simvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	178/433 (41.11%)		190/452 (42.04%)
Blood and lymphatic system disorders
Cavernous Hemangioma ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	2
Cardiac disorders
Rheumatic Heart Disease ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Ischemic Heart Disease ^† 1	4/433 (0.92%)	4	6/452 (1.33%)	6
Pulmonary Circulation disorders ^† 1	4/433 (0.92%)	5	6/452 (1.33%)	6
Pericarditis ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Cardiomyopathy ^† 1	2/433 (0.46%)	2	0/452 (0.00%)	0
Cardiac Dysrhythmias ^† 1	7/433 (1.62%)	7	4/452 (0.88%)	5
Heart Failure ^† 1	4/433 (0.92%)	6	5/452 (1.11%)	7
Tachycardia ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Eye disorders
Orbital cellulitis ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Gastrointestinal disorders
Esophagus and stomach disorders ^† 1	1/433 (0.23%)	1	5/452 (1.11%)	5
Appendicitis ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Abdominal Hernia ^† 1	2/433 (0.46%)	2	2/452 (0.44%)	2
Enteritis ^† 1	3/433 (0.69%)	3	0/452 (0.00%)	0
Other Intestinal disorders ^† 1	7/433 (1.62%)	9	5/452 (1.11%)	5
Other Digestive Disorders ^† 1	11/433 (2.54%)	14	7/452 (1.55%)	8
Nissen Fundoplication ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Ill defined digestive symptoms ^† 1	1/433 (0.23%)	1	2/452 (0.44%)	2
General disorders
Syncope ^† 1	5/433 (1.15%)	5	1/452 (0.22%)	1
Dizziness ^† 1	2/433 (0.46%)	2	0/452 (0.00%)	0
Severe Headaches ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Ill defined abdominal pain ^† 1	2/433 (0.46%)	2	3/452 (0.66%)	4
Sudden death of unknown cause ^† 1	4/433 (0.92%)	4	4/452 (0.88%)	4
Complications of surgical and medical care ^† 1	4/433 (0.92%)	4	2/452 (0.44%)	2
Respiratory Arrest ^† 1	2/433 (0.46%)	2	1/452 (0.22%)	1
Abnormal Gait ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Epistaxis ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Sepsis ^† 1	1/433 (0.23%)	1	4/452 (0.88%)	4
Fatigue ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Infections and infestations
Bacterial Infection ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Viral Infection ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Other Infection ^† 1 [1]	0/433 (0.00%)	0	1/452 (0.22%)	1
Injury, poisoning and procedural complications
Fractures ^† 1	7/433 (1.62%)	7	4/452 (0.88%)	4
Sprain ^† 1	1/433 (0.23%)	1	1/452 (0.22%)	1
Intracranial injury ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Internal Injury ^† 1	1/433 (0.23%)	2	1/452 (0.22%)	1
Contusion ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Trauma from motorcycle accident ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Poisoning ^† 1	1/433 (0.23%)	1	1/452 (0.22%)	1
Concussion ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Metabolism and nutrition disorders
Metabolic disorders ^† 1	5/433 (1.15%)	6	5/452 (1.11%)	5
Musculoskeletal and connective tissue disorders
Arthropathy ^† 1	1/433 (0.23%)	1	5/452 (1.11%)	6
Dorsopathy ^† 1	4/433 (0.92%)	4	3/452 (0.66%)	3
Rheumatism ^† 1	3/433 (0.69%)	3	1/452 (0.22%)	1
Osteopathy ^† 1	2/433 (0.46%)	2	1/452 (0.22%)	1
Spondylolisthesis ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Degenerative Disc Disease ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Liver Cancer ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	2
Respiratory Cancer ^† 1	9/433 (2.08%)	12	10/452 (2.21%)	14
Bone Neoplasm ^† 1	1/433 (0.23%)	1	4/452 (0.88%)	4
Genitourinary Neoplasm ^† 1	4/433 (0.92%)	5	5/452 (1.11%)	7
Squamous Cell Carcinoma ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Lymphatic Neoplasm ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Neuroendocrine Neoplasm ^† 1	1/433 (0.23%)	1	1/452 (0.22%)	1
Nervous system disorders
Central Nervous System disorders ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Pain ^† 1	0/433 (0.00%)	0	2/452 (0.44%)	2
Seizure ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Psychiatric disorders
Mental Disorder ^† 1	3/433 (0.69%)	4	5/452 (1.11%)	6
Altered Mental Status ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
Renal and urinary disorders
Nephrotic disorders ^† 1	2/433 (0.46%)	2	0/452 (0.00%)	0
Other Urinary Disorder ^† 1	5/433 (1.15%)	5	5/452 (1.11%)	5
Disorders of the Male Genitourinary System ^† 1	0/433 (0.00%)	0	2/452 (0.44%)	3
Disorders of the Female Genitourinary System ^† 1	1/433 (0.23%)	1	1/452 (0.22%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Infection ^† 1	1/433 (0.23%)	3	1/452 (0.22%)	1
Pneumonia ^† 1	34/433 (7.85%)	40	27/452 (5.97%)	32
Influenza ^† 1	5/433 (1.15%)	5	6/452 (1.33%)	9
Bronchitis ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	2
Emphysema ^† 1	3/433 (0.69%)	3	1/452 (0.22%)	1
Pneumoconioses ^† 1	0/433 (0.00%)	0	1/452 (0.22%)	1
COPD Exacerbation ^† 1	96/433 (22.17%)	155	97/452 (21.46%)	187
COPD other ^† 1	9/433 (2.08%)	9	10/452 (2.21%)	15
Other Respiratory ^† 1	12/433 (2.77%)	14	13/452 (2.88%)	20
Ill Defined Respiratory events ^† 1	10/433 (2.31%)	11	13/452 (2.88%)	15
Hypoxemia ^† 1	0/433 (0.00%)	0	2/452 (0.44%)	2
Skin and subcutaneous tissue disorders
Skin Infection ^† 1	2/433 (0.46%)	2	3/452 (0.66%)	4
Cellulitis ^† 1	1/433 (0.23%)	1	0/452 (0.00%)	0
Vascular disorders
Cerebrovascular ^† 1	1/433 (0.23%)	1	6/452 (1.33%)	6
Artery disorder ^† 1	2/433 (0.46%)	2	2/452 (0.44%)	3
Vein disorder ^† 1	4/433 (0.92%)	4	3/452 (0.66%)	4
† Indicates events were collected by systematic assessment 1 Term from vocabulary, ICD-9 [1] Pulmonary Aspergillosis
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Simvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	316/433 (72.98%)		329/452 (72.79%)
General disorders
Headache ^† 1	16/433 (3.70%)	20	23/452 (5.09%)	27
Musculoskeletal and connective tissue disorders
Arthropathies ^† 1	25/433 (5.77%)	38	32/452 (7.08%)	43
Dorsopathies ^† 1	27/433 (6.24%)	35	27/452 (5.97%)	32
Rheumatism ^† 1	67/433 (15.47%)	89	54/452 (11.95%)	73
Renal and urinary disorders
Urinary Infection ^† 1	26/433 (6.00%)	56	23/452 (5.09%)	30
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Infection ^† 1	109/433 (25.17%)	159	107/452 (23.67%)	166
Pneumonia ^† 1	22/433 (5.08%)	25	17/452 (3.76%)	19
COPD Exacerbation ^† 1	232/433 (53.58%)	642	244/452 (53.98%)	649
Other COPD Related Symptoms ^† 1	41/433 (9.47%)	79	43/452 (9.51%)	80
Dyspnea ^† 1	65/433 (15.01%)	94	59/452 (13.05%)	90
† Indicates events were collected by systematic assessment 1 Term from vocabulary, ICD-9

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.

More Information

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Sarah Lindberg
Organization:	University of Minnesota
Phone:	612-626-9011
EMail:	sharnden@ccbr.umn.edu

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

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.

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.

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.

Layout table for additonal information

Responsible Party:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT01061671
Other Study ID Numbers:	689 U10HL074424 ( U.S. NIH Grant/Contract )
First Submitted:	February 2, 2010
First Posted:	February 3, 2010
Results First Submitted:	January 29, 2015
Results First Posted:	March 26, 2015
Last Update Posted:	January 2, 2018

To Top