Hyperlipidemia, Hypercholesterolemia
Conditions
Keywords
ezetimibe, niacin, colestipol, hyperlipidemia, adjunct therapy, zetia
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.
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.
Interventions
Sponsors
American Society of Health-System Pharmacists Research and Education Foundation
Tuscaloosa Research & Education Advancement Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LDL Goal Attainment | 12 weeks | Each participant had his LDL goal calculated based on the NCEP ATPIII guidelines. |
Secondary
| Measure | Time frame |
|---|---|
| LFT Elevation | 12 weeks |
| Incidents of Rhabdomyolysis | 12 weeks |
| Change in HDL From Baseline to 12 Weeks. | baseline and 12 weeks |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from 2005-2007 from primary care medical clinics.
Pre-assignment details
Patients had to be on max tolerated dose of a statin and need additional LDL lowering.
Participants by arm
| Arm | Count |
|---|---|
| Niacin Niacin added to max tolerated dose of statin | 10 |
| Colestipol Colestipol added to max dose statin | 10 |
| Ezetimibe Ezetimibe added to max tolerated dose statin | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Niacin | Colestipol | Ezetimibe | Total |
|---|---|---|---|---|
| Age, Customized Age =>50 | 10 participants | 10 participants | 10 participants | 30 participants |
| Region of Enrollment United States | 10 participants | 10 participants | 10 participants | 30 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 3 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
LDL Goal Attainment
Each participant had his LDL goal calculated based on the NCEP ATPIII guidelines.
Time frame: 12 weeks
Population: intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin | LDL Goal Attainment | 6 participants |
| Colestipol | LDL Goal Attainment | 6 participants |
| Ezetimibe | LDL Goal Attainment | 9 participants |
Secondary
Change in HDL From Baseline to 12 Weeks.
Time frame: baseline and 12 weeks
Population: Change in HDL
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Niacin | Change in HDL From Baseline to 12 Weeks. | baseline | 42.33 mg/dl | Standard Deviation 11.2 |
| Niacin | Change in HDL From Baseline to 12 Weeks. | 12 weeks | 43.00 mg/dl | Standard Deviation 11.62 |
| Colestipol | Change in HDL From Baseline to 12 Weeks. | baseline | 39.22 mg/dl | Standard Deviation 14.22 |
| Colestipol | Change in HDL From Baseline to 12 Weeks. | 12 weeks | 37.56 mg/dl | Standard Deviation 7.83 |
| Ezetimibe | Change in HDL From Baseline to 12 Weeks. | baseline | 32.90 mg/dl | Standard Deviation 5.15 |
| Ezetimibe | Change in HDL From Baseline to 12 Weeks. | 12 weeks | 34.70 mg/dl | Standard Deviation 10.39 |
Secondary
Incidents of Rhabdomyolysis
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Niacin | Incidents of Rhabdomyolysis | 0 participants | 30.55 |
| Colestipol | Incidents of Rhabdomyolysis | 0 participants | 12.97 |
| Ezetimibe | Incidents of Rhabdomyolysis | 0 participants | 20.07 |
Secondary
LFT Elevation
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Niacin | LFT Elevation | 1 participants |
| Colestipol | LFT Elevation | 1 participants |
| Ezetimibe | LFT Elevation | 2 participants |