CPC: Evaluate Carotid Artery Plaque Composition by Magnetic Resonance Imaging in People Receiving Cholesterol Medication

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00715273
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Pfizer (Industry), Abbott (Industry), Daiichi Sankyo, Inc. (Industry), Upsher-Smith Laboratories (Industry)
• Enrollment: 217
• Locations: 4
• Arms: 3
• Actual Duration (Months): 214
• Patients Per Site: 54.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Atherosclerosis is a condition that occurs when fatty deposits build up along the inner walls of arteries. This study will examine the effectiveness of a combination of cholesterol-lowering medications at decreasing the fat content of atherosclerotic deposits in people who have coronary artery disease or carotid artery disease.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis	Drug: Atorvastatin; Drug: Niacin; Drug: Colesevelam; Drug: Placebo Niacin; Drug: Placebo Colesevelam	Phase 4

Detailed Description

Atherosclerosis is a condition in which deposits of fat, cholesterol, and other substances build up along the inner walls of arteries; these deposits are known as plaque. People with atherosclerosis are at risk of developing coronary artery disease, in which plaque build-up occurs in the arteries that supply blood to the heart, and carotid artery disease, in which plaque build-up occurs in the arteries that deliver blood through the neck to the brain. These conditions can lead to blood clots, heart attack, and stroke. Research has shown that people who have more fat content in atherosclerotic plaque may have a higher risk of experiencing a heart attack or stroke. Treatments for atherosclerosis include lifestyle changes, medicines, and medical procedures or surgery. There are several medications that can aid people in controlling their cholesterol levels, including atorvastatin, a medication that inhibits the production of cholesterol; niacin, a B-complex vitamin that can reduce cholesterol levels in combination with dietary changes; and colesevelam, a medication that inhibits fat absorption. Using magnetic resonance imaging (MRI), this study will evaluate whether these medications, alone or in combination, can decrease the fat content of atherosclerotic plaques within the carotid arteries of people with coronary artery disease and carotid artery disease.

This study will enroll people with coronary artery disease or carotid artery disease.

Participants will be randomly assigned to one of the following 40-month treatment groups:

• Group 1 participants will receive atorvastatin, placebo niacin, and placebo colesevelam each day.

• Group 2 participants will receive atorvastatin, niacin, and placebo colesevelam each day.

• Group 3 participants will receive atorvastatin, niacin, and colesevelam each day.

At a baseline study visit, participants will undergo a blood collection and will receive dietary counseling that will focus on lowering cholesterol levels. They will also undergo an MRI scan of their carotid arteries. For the next 4 months, participants will attend monthly study visits for repeat blood collection and dietary counseling; for the subsequent 36 months, participants will attend study visits every other month. Repeat carotid artery MRI scans will occur at Months 12, 24, and 36. At three different times during the study, researchers will ask participants to record their food consumption for 3 consecutive days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Carotid Plaque Composition by Magnetic Resonance Imaging During Lipid Lowering Therapy
• Actual Study Start Date: May 1, 2001
• Actual Primary Completion Date: Dec 12, 2018
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 - single therapy group Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group.	Drug: Atorvastatin; 10 to 80 mg of atorvastatin each day; Other Names: Lipitor ; Drug: Placebo Niacin; Placebo niacin each day; Drug: Placebo Colesevelam; Placebo colesevelam each day
Experimental: 2 - double therapy group Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group.	Drug: Atorvastatin; 10 to 80 mg of atorvastatin each day; Other Names: Lipitor ; Drug: Niacin; 2000 mg of niacin each day; Other Names: Niaspan Slo-niacin ; Drug: Placebo Colesevelam; Placebo colesevelam each day
Experimental: 3 - triple therapy group Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group	Drug: Atorvastatin; 10 to 80 mg of atorvastatin each day; Other Names: Lipitor ; Drug: Niacin; 2000 mg of niacin each day; Other Names: Niaspan Slo-niacin ; Drug: Colesevelam; 3.8 g of colesevelam each day; Other Names: WelChol

Outcome Measures

Primary Outcome Measures

1. Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI [Measured at Years 1, 2, and 3]

   The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course. Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.

2. Annualized LRNC and Wall Volume Changes in Carotid Plaque Composition, as Assessed by MRI [Measured at Years 1, 2, and 3]

   The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course. Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.

Secondary Outcome Measures

1. Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions [Measured at Years 3, 4, and 5]

   Any cardiovascular events such as death from any cause, nonfatal myocardial infarction, stroke, and revascularization procedures (PCI or CABG) due to unstable ischemia will be recorded and verified.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinically established coronary artery disease or carotid artery disease with greater than 15% stenosis by ultrasound

• Family history of cardiovascular disease

• Apolipoprotein B level greater than or equal to 120 mg/dL (LDL level should be between 100 and 190 mg/dL without medication)

• Has been undergoing lipid therapy for no more than 12 months before study entry

• Medically stable

• Medically able to undergo MRI procedure

Exclusion Criteria:

• Uses pacemaker or has metallic implants

• Has immediate plans for carotid endarterectomy

• History of alcohol or drug abuse

• Active liver disease or liver dysfunction, defined by elevations in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal

• Serum creatine kinase (CK) level greater than 3 times the upper limit of normal before study entry

• Serum creatinine level greater than 2.5 times the upper limit of normal

• Diabetes, with a fasting glucose level greater than 150 mg/dL or hemoglobin A1c (HbA1c) level greater than 8% before study entry

• Uncontrolled high blood pressure, defined as average resting systolic blood pressure greater than 200 mm Hg or average resting diastolic blood pressure greater than 95 mm Hg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90089
2	St. Luke's Idaho Cardiology	Boise	Idaho	United States	83712
3	University of Washington Coronary Atherosclerosis Research Lab	Seattle	Washington	United States	98104
4	Yakima Heart Center	Yakima	Washington	United States	98902

Sponsors and Collaborators

• University of Washington
• National Heart, Lung, and Blood Institute (NHLBI)
• Pfizer
• Abbott
• Daiichi Sankyo, Inc.
• Upsher-Smith Laboratories

Investigators

• Principal Investigator: Xue-Qiao Zhao, MD, University of Washington

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 6, 2016

More Information

Publications

None provided.

• Responsible Party: Xue-Qiao Zhao, Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT00715273
• Other Study ID Numbers: STUDY00001165; R01HL063895-05A1
• First Posted: Jul 15, 2008
• Last Update Posted: Jun 7, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Xue-Qiao Zhao, Professor, University of Washington: Magnetic Resonance Imaging; Atherosclerotic Plaque; Lipid Lowering Therapy
• Additional relevant MeSH terms: Carotid Artery Diseases; Coronary Artery Disease; Atherosclerosis; Niacin; Niacinamide; Nicotinic Acids; Atorvastatin; Colesevelam Hydrochloride

Study Results

Participant Flow

Arm/Group Title	1 - Single Therapy Group	2 - Double Therapy Group	3 - Triple Therapy Group
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day
Period Title: Overall Study
STARTED	71	73	73
COMPLETED	63	65	68
NOT COMPLETED	8	8	5

Baseline Characteristics

Arm/Group Title	1 - Single Therapy Group	2 - Double Therapy Group	3 - Triple Therapy Group	Total
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day	Total of all reporting groups
Overall Participants	71	73	73	217
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	60 84.5%	62 84.9%	60 82.2%	182 83.9%
>=65 years	11 15.5%	11 15.1%	13 17.8%	35 16.1%
Sex: Female, Male (Count of Participants)
Female	28 39.4%	30 41.1%	30 41.1%	88 40.6%
Male	43 60.6%	43 58.9%	43 58.9%	129 59.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 12.7%	12 16.4%	10 13.7%	31 14.3%
Not Hispanic or Latino	62 87.3%	61 83.6%	63 86.3%	186 85.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.4%	0 0%	1 0.5%
Asian	3 4.2%	3 4.1%	5 6.8%	11 5.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	3 4.1%	2 2.7%	5 2.3%
White	65 91.5%	65 89%	64 87.7%	194 89.4%
More than one race	3 4.2%	1 1.4%	2 2.7%	6 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	71 100%	73 100%	73 100%	217 100%
Family history of premature cardiovascular disease, n (%) (Count of Participants)
Count of Participants [Participants]	34 47.9%	36 49.3%	36 49.3%	106 48.8%
History of myocardial infarction, n (%) (Count of Participants)
Count of Participants [Participants]	25 35.2%	26 35.6%	31 42.5%	82 37.8%
Established coronary artery disease, n (%) (Count of Participants)
Count of Participants [Participants]	62 87.3%	60 82.2%	67 91.8%	189 87.1%
Hypertension, n (%) (Count of Participants)
Count of Participants [Participants]	42 59.2%	44 60.3%	44 60.3%	130 59.9%
Diabetes, n (%) (Count of Participants)
Count of Participants [Participants]	10 14.1%	13 17.8%	9 12.3%	32 14.7%
Current smoking, n (%) (Count of Participants)
Count of Participants [Participants]	13 18.3%	17 23.3%	15 20.5%	45 20.7%

Outcome Measures

1. Primary Outcome

Title	Annualized LRNC Volume Change in Carotid Plaque Composition, as Assessed by MRI
Description	The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course. Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.
Time Frame	Measured at Years 1, 2, and 3

Outcome Measure Data

Analysis Population Description

Analysis group was limited from total study population due to the need for detectable lipid-rich necrotic core (LRNC) measurement at study baseline.

Arm/Group Title	1 - Single Therapy Group	2 - Double Therapy Group	3 - Triple Therapy Group
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day
Measure Participants	60	61	61
Mean (Standard Error) [mm^3/year]	-4.6 (5.0)	-15.1 (3.2)	-9.4 (3.0)

2. Secondary Outcome

Title	Composite of Cardiovascular Endpoints: Number of Participants With Cardiovascular Disease Death, Non-fatal Heart Attack, Stroke, and Worsening Ischemia Requiring Medical Interventions
Description	Any cardiovascular events such as death from any cause, nonfatal myocardial infarction, stroke, and revascularization procedures (PCI or CABG) due to unstable ischemia will be recorded and verified.
Time Frame	Measured at Years 3, 4, and 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 - Single Therapy Group	2 - Double Therapy Group	3 - Triple Therapy Group
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day
Measure Participants	71	73	73
Composite Measured at Year 3	6 8.5%	6 8.2%	7 9.6%
Composite Measured at Year 4 (cumulative)	7 9.9%	11 15.1%	9 12.3%
Composite Measured at Year 5 (cumulative)	9 12.7%	11 15.1%	9 12.3%

3. Primary Outcome

Title	Annualized LRNC and Wall Volume Changes in Carotid Plaque Composition, as Assessed by MRI
Description	The primary endpoint of this study is carotid plaque lipid composition identified by MRI. The determination of plaque lipid content for each carotid artery will be performed using the automated interactive system. These measurements will be performed from the MRI scans at four time points blinded to time sequence of MRI examinations, patient treatment, lipid levels and clinical course. Volume Measurements: Contours were placed around the lumen, outer-wall boundaries, and plaque features of carotid artery. (Arterial wall area) = (outer-wall area) - (lumen area). Volume calculated as: area x 2 mm (slice thickness). Tissue volume/wall volume x (100%) is presented as percentage. Annualized change presented mm^3/year (for volume) and as percentage change/year.
Time Frame	Measured at Years 1, 2, and 3

Outcome Measure Data

Analysis Population Description

Analysis group was limited from total study population due to the need for detectable lipid-rich necrotic core (LRNC) measurement at study baseline.

Arm/Group Title	1 - Single Therapy Group	2 - Double Therapy Group	3 - Triple Therapy Group
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day	Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day
Measure Participants	60	61	61
LRNC change	-1.6 (1.1)	-3.6 (0.8)	-2.8 (0.7)
Wall Volume change	-0.6 (0.5)	-1.4 (0.4)	-1.2 (0.5)

Adverse Events

Time Frame	Period of time from study baseline visit until subject completion. Subject followed for up to 168 months in open label follow-up period.
Arm/Group Title	1 - Single Therapy Group		2 - Double Therapy Group		3 - Triple Therapy Group
Arm/Group Description	Participants will receive atorvastatin, placebo niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the single therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Placebo Niacin: Placebo niacin each day Placebo Colesevelam: Placebo colesevelam each day		Participants will receive atorvastatin, niacin, and placebo colesevelam. The treatment target for LDL-C will be ≤80 mg/dl for the double therapy group. Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Placebo Colesevelam: Placebo colesevelam each day		Participants will receive atorvastatin, niacin, and colesevelam. The treatment target for LDL-C will be ≤60 mg/dl for the triple therapy group Atorvastatin: 10 to 80 mg of atorvastatin each day Niacin: 2000 mg of niacin each day Colesevelam: 3.8 g of colesevelam each day
All Cause Mortality
	1 - Single Therapy Group		2 - Double Therapy Group		3 - Triple Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/71 (9.9%)		7/73 (9.6%)		3/73 (4.1%)
Serious Adverse Events
	1 - Single Therapy Group		2 - Double Therapy Group		3 - Triple Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/71 (36.6%)		20/73 (27.4%)		20/73 (27.4%)
Cardiac disorders
Myocardial infarction	3/71 (4.2%)	3	4/73 (5.5%)	4	4/73 (5.5%)	4
Percutaneous coronary intervention	10/71 (14.1%)	13	6/73 (8.2%)	10	8/73 (11%)	8
Hospitalized for worsening ischemia	7/71 (9.9%)	9	7/73 (9.6%)	9	5/73 (6.8%)	6
Hospitalized for heart failure	1/71 (1.4%)	2	0/73 (0%)	2	1/73 (1.4%)	1
Death - myocardial infarction	1/71 (1.4%)	1	1/73 (1.4%)	1	0/73 (0%)	0
Death - Coronary artery disease	2/71 (2.8%)	2	1/73 (1.4%)	1	0/73 (0%)	0
General disorders
Stroke	2/71 (2.8%)	2	1/73 (1.4%)	1	0/73 (0%)	0
Death - Intentional self-harm	0/71 (0%)	0	0/73 (0%)	0	1/73 (1.4%)	1
Death - Other/Multiple/Unknown	3/71 (4.2%)	3	2/73 (2.7%)	2	0/73 (0%)	0
Musculoskeletal and connective tissue disorders
Diseased or injured hip joint requiring replacement	0/71 (0%)	0	1/73 (1.4%)	1	2/73 (2.7%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	2/71 (2.8%)	2	3/73 (4.1%)	3	4/73 (5.5%)	4
Death - Cancer	1/71 (1.4%)	1	2/73 (2.7%)	2	2/73 (2.7%)	2
Respiratory, thoracic and mediastinal disorders
Death - Idiopathic Pulmonary Fibrosis	0/71 (0%)	0	1/73 (1.4%)	1	0/73 (0%)	0
Surgical and medical procedures
Coronary artery bypass graft surgery	1/71 (1.4%)	1	2/73 (2.7%)	2	1/73 (1.4%)	1
Vascular disorders
Peripheral artery revascularization	2/71 (2.8%)	3	2/73 (2.7%)	2	3/73 (4.1%)	3
Hospitalized for transient ischemic attack	2/71 (2.8%)	2	2/73 (2.7%)	2	1/73 (1.4%)	1
Other (Not Including Serious) Adverse Events
	1 - Single Therapy Group		2 - Double Therapy Group		3 - Triple Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/71 (47.9%)		40/73 (54.8%)		32/73 (43.8%)
Blood and lymphatic system disorders
Anemia	1/71 (1.4%)	1	4/73 (5.5%)	4	1/73 (1.4%)	1
Cardiac disorders
Angina	3/71 (4.2%)	4	9/73 (12.3%)	12	6/73 (8.2%)	8
Endocrine disorders
New onset Type 2 Diabetes Melitus	4/61 (6.6%)	4	5/60 (8.3%)	5	3/64 (4.7%)	3
Gastrointestinal disorders
Gastroenteritis	2/71 (2.8%)	2	5/73 (6.8%)	5	4/73 (5.5%)	4
General disorders
Muscle aches	5/71 (7%)	5	1/73 (1.4%)	2	3/73 (4.1%)	3
Leg pain	2/71 (2.8%)	3	7/73 (9.6%)	7	6/73 (8.2%)	6
Headache	5/71 (7%)	5	6/73 (8.2%)	6	2/73 (2.7%)	2
Dizziness	1/71 (1.4%)	1	9/73 (12.3%)	12	2/73 (2.7%)	2
Infections and infestations
Sinus infection	6/71 (8.5%)	6	0/73 (0%)	0	2/73 (2.7%)	2
Upper respiratory infection	9/71 (12.7%)	13	11/73 (15.1%)	11	8/73 (11%)	10
Influenza	3/71 (4.2%)	4	8/73 (11%)	10	3/73 (4.1%)	3
Musculoskeletal and connective tissue disorders
Back pain	2/71 (2.8%)	2	3/73 (4.1%)	3	7/73 (9.6%)	7
Renal and urinary disorders
Kidney stone	2/71 (2.8%)	2	0/73 (0%)	0	4/73 (5.5%)	5
Respiratory, thoracic and mediastinal disorders
Pneumonia	5/71 (7%)	5	1/73 (1.4%)	1	1/73 (1.4%)	1
Surgical and medical procedures
Diseased or injured knee joint requiring surgery	6/71 (8.5%)	6	3/73 (4.1%)	3	3/73 (4.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.