A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction

• Sponsor: Tuscaloosa Research & Education Advancement Corporation (Other)
• Overall Status: Completed
• CT.gov ID: NCT00203476
• Collaborator: American Society of Health-System Pharmacists Research and Education Foundation (Other)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 32
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

To compare LDL reduction compared to baseline in patients using maximum tolerated HMG CoA Reductase inhibitor (statin) therapy with adjunctive therapy with ezetimibe, colestipol, or niacin. The patient's cardiovascular risks are assessed to determine if National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) guidelines for low density lipoprotein (LDL) reduction were achieved between the three groups. Secondary measures examine the safety issues with liver function test (LFT) monitoring and rhabdomyolysis. High-density lipoproteins (HDL) elevations are monitored between the three groups to determine efficacy as a secondary outcome.

Condition or Disease	Intervention/Treatment	Phase
Hyperlipidemia; Hypercholesterolemia	Drug: Niacin; Drug: Colestipol; Drug: Ezetimibe	Phase 4

Detailed Description

: Patients with hyperlipidemia who sign consent and who are currently at maximum tolerated dose of a statin and are not meeting NCEP ATPIII treatment goals for LDL cholesterol are enrolled in 12-week open label, prospective trial. Patients are randomized into one of three groups to receive ezetimibe, niacin, or colestipol in addition to current statin therapy. Patients are titrated as tolerated to therapeutic doses of study medications (ezetimibe 10mg/day, niacin 1500mg/day, and colestipol 20gm/day). At baseline, informed consent; a laboratory admission profile (Chem20); weight; height; blood pressure; concomitant medications; cholesterol medication history; and grapefruit juice consumption data are gathered. At weeks 6 and 12, patients have their cholesterol panels and liver function tests assessed. Patients are also interviewed regarding side effects (including rhabdomyolysis), tolerance, changes in concomitant medications, and grapefruit juice consumption, along with weight and blood pressure measurements.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Statin with Niacin Niacin dose range of 500-1500mg (average 888mg)	Drug: Niacin
Active Comparator: Statin with Colestipol Colestipol dose range 5-15gm (average 9.5gm)	Drug: Colestipol
Active Comparator: Statin with Ezitimibe Ezitimibe 10mg (average 10mg)	Drug: Ezetimibe; Other Names: Zetia

Outcome Measures

Primary Outcome Measures

1. LDL Goal Attainment [12 weeks]

   Each participant had his LDL goal calculated based on the NCEP ATPIII guidelines.

Secondary Outcome Measures

1. LFT Elevation [12 weeks]

2. Incidents of Rhabdomyolysis [12 weeks]

3. Change in HDL From Baseline to 12 Weeks. [baseline and 12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Veterans eligible for treatment at the Tuscaloosa VA Medical Center

• 50 years of age

• Male or female

• Any race or ethnic group

• Signed informed consent

• Hyperlipidemia despite current maximum tolerated dose of an HMG CoA Reductase inhibitor (statin) for > 6 weeks

• Currently not meeting NCEP ATPIII treatment goals for LDL cholesterol

Exclusion Criteria:

• Known hypersensitivity or intolerance to ezetimibe, niacin, or colestipol

• Previous failed adequate trial of adjunctive ezetimibe, niacin, or colestipol

• Consumes more than 8oz. grapefruit juice daily

• Significant medical condition that would impact safety evaluations (i.e. significantly elevated LFT, hepatitis, severe dermatitis, uncontrolled diabetes, severe GI disease, fibromyalgia, renal failure, recent CVA or MI, pancreatitis, etc.)

• Receiving medications that would be contraindicated to use in combination with ezetimibe, niacin, or colestipol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tuscaloosa Research & Education Advancement Corporation	Tuscaloosa	Alabama	United States	35404

Sponsors and Collaborators

• Tuscaloosa Research & Education Advancement Corporation
• American Society of Health-System Pharmacists Research and Education Foundation

Investigators

• Principal Investigator: Raela B Williford, PharmD, Tuscaloosa Veterans Affairs Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ansell BJ. Rationale for combination therapy with statin drugs in the treatment of dyslipidemia. Curr Atheroscler Rep. 2005 Feb;7(1):29-33. Review.

• Responsible Party: Raela Williford, PharmD, Clinical Pharmacist/PI, Tuscaloosa Research & Education Advancement Corporation
• ClinicalTrials.gov Identifier: NCT00203476
• Other Study ID Numbers: TREAC Cholesterol Study; TREAC Cholesterol Study
• First Posted: Sep 20, 2005
• Last Update Posted: Aug 12, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Raela Williford, PharmD, Clinical Pharmacist/PI, Tuscaloosa Research & Education Advancement Corporation: ezetimibe; niacin; colestipol; hyperlipidemia; adjunct therapy; zetia
• Additional relevant MeSH terms: Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Niacin; Ezetimibe; Colestipol

Study Results

Participant Flow

Recruitment Details	Patients were recruited from 2005-2007 from primary care medical clinics.
Pre-assignment Detail	Patients had to be on max tolerated dose of a statin and need additional LDL lowering.

Arm/Group Title	Niacin	Colestipol	Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin
Period Title: Overall Study
STARTED	10	10	10
COMPLETED	9	9	10
NOT COMPLETED	1	1	0

Baseline Characteristics

Arm/Group Title	Niacin	Colestipol	Ezetimibe	Total
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin	Total of all reporting groups
Overall Participants	10	10	10	30
Age, Customized (participants) [Number]
Age =>50	10 100%	10 100%	10 100%	30 100%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	10 100%	10 100%	10 100%	30 100%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	10 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	LDL Goal Attainment
Description	Each participant had his LDL goal calculated based on the NCEP ATPIII guidelines.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Niacin	Colestipol	Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin
Measure Participants	9	9	10
Number [participants]	6 60%	6 60%	9 90%

2. Secondary Outcome

Title	LFT Elevation
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Niacin	Colestipol	Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin
Measure Participants	9	9	10
Number [participants]	1 10%	1 10%	2 20%

3. Secondary Outcome

Title	Incidents of Rhabdomyolysis
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Niacin	Colestipol	Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin
Measure Participants	9	9	10
Number [participants]	0 (30.55) 0%	0 (12.97) 0%	0 (20.07) 0%

4. Secondary Outcome

Title	Change in HDL From Baseline to 12 Weeks.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Change in HDL

Arm/Group Title	Niacin	Colestipol	Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin	Colestipol added to max dose statin	Ezetimibe added to max tolerated dose statin
Measure Participants	9	9	10
baseline	42.33 (11.20)	39.22 (14.22)	32.90 (5.15)
12 weeks	43.00 (11.62)	37.56 (7.83)	34.70 (10.39)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Niacin		Colestipol		Ezetimibe
Arm/Group Description	Niacin added to max tolerated dose of statin		Colestipol added to max dose statin		Ezetimibe added to max tolerated dose statin
All Cause Mortality
	Niacin		Colestipol		Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Niacin		Colestipol		Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Niacin		Colestipol		Ezetimibe
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/10 (60%)		3/10 (30%)		3/10 (30%)
Gastrointestinal disorders
Indestion and belching	0/10 (0%)		0/10 (0%)		1/10 (10%)
Loose Stools	1/10 (10%)		0/10 (0%)		0/10 (0%)
Flatulence	0/10 (0%)		1/10 (10%)		0/10 (0%)
Constipation	0/10 (0%)		1/10 (10%)		0/10 (0%)
Hepatobiliary disorders
Elevated LFTs	1/10 (10%)		1/10 (10%)		2/10 (20%)
Skin and subcutaneous tissue disorders
Flushing	5/10 (50%)		0/10 (0%)		0/10 (0%)
Rash	0/10 (0%)		1/10 (10%)		0/10 (0%)
Vascular disorders
Edema	0/10 (0%)		1/10 (10%)		0/10 (0%)

Limitations/Caveats

Open label.

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.