HIV Infections, Hypercholesterolemia
Conditions
Keywords
Hypercholesterolemia, HIV, Ezetimibe, Statin, Apolipoprotein B100/Apolipoprotein A1 ratio
Brief summary
This study involves comparing the effectiveness of treatments in HIV positive patients who may be predisposed to heart attack or stroke. The investigators will evaluate the effectiveness of two drugs, often prescribed by doctors to these patients, at lowering cholesterol and thereby making the patient less them less vulnerable to suffering a heart attack or stroke. The investigators believe that the addition of a second drug, from a different class of cholesterol lowering medications, will improve the outcome of the patients by lowering cholesterol.
Detailed description
This study seeks to determine whether HIV positive patients who have suboptimal lipids and/or are not reaching specified lipid targets will benefit from the addition of a second lipid lowering drug (ezetimibe) to existing lipid lowering therapy with a statin (specifically rosuvastatin) versus increasing the dose of the ongoing statin in terms of improvements in serum lipid parameters namely total cholesterol, LDL, HDL, triglycerides and apolipoprotein B100 (apoB), apolipoprotein A1 (apoA1), apoB/apoA1 ratio. The target population will be HIV+ patients with hypercholesterolemia due to highly active antiretroviral therapy, the study will have a randomized, parallel design. Sample size will be 50 patients already taking 10 mg of rosuvastatin who are not reaching lipid targets to receive either an increased dose of rosuvastatin (20mg) or to receive 10mg ezetimibe in addition to their ongoing rosuvastatin therapy. There will be 25 patients randomized to each group. At baseline serum samples will be obtained and tested for serum triglycerides, total cholesterol, HDL, total cholesterol:HDL ratio, apoB, apoA1, apoB/apoA1 ratio, liver transaminases (AST and ALT), CK, thyroid stimulating hormone, creatinine and fasting blood glucose. After 12 weeks of therapy serum samples will once again be obtained and tested for serum triglycerides, total cholesterol, HDL, total cholesterol:HDL ratio, apolipoprotein B100, liver transaminases (AST and ALT), CK, thyroid stimulating hormone, creatinine and fasting blood glucose. The primary hypothesis is that the combination of rosuvastatin and ezetimibe will lower serum apolipoprotein B100/apolipoprotein A1 ratio more so than an increased dose of rosuvastatin alone, in participants with mixed dyslipidemia associated with HIV therapy. Secondarily we believe the combination of rosuvastatin and ezetimibe will lower the concentrations of serum cholesterol, LDL-cholesterol, triglycerides, apolipoprotein B100 and C-reactive protein more so than an increased dose of rosuvastatin alone, and that there will be no increase in side effects when administered to participants with mixed dyslipidemia associated with HIV therapy.
Interventions
DRUGEzetimibe
10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)- tablet, orally, 10mg/day for 12 weeks
DRUGRosuvastatin (standard care)
Increased dose of rosuvastatin to 20mg/day
Sponsors
Merck Frosst-Schering Pharma, G.P.
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV positive * currently taking 10mg of rosuvastatin * recent (within three months) fasting lipid profile in which the serum total cholesterol to HDL ratio is \>5.0
Exclusion criteria
* Previous adverse reaction to ezetimibe * taken ezetimibe within 30 days of starting the study * history of vascular disease * allergic reaction or muscle problems while taking any statin * currently taking other lipid lowering medications (i.e. a fibrates or cholestyramine)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Endpoint is the Difference in Final Value of Serum Apolipoprotein B Between Participants Treated With Rosuvastatin Versus Participants Treated With Both Rosuvastatin and Ezetimibe. | 3 months from baseline |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change in Apolipoprotein B, Percent and Absolute Change Total Cholesterol, LDL, HDL, Triglycerides, Apolipoprotein A1, apolipoproteinB/apoliporoteinA1 Ratio and C-reactive Protein | 3 months from baseline |
| Assessment of Safety Parameters, Specifically Incidence of Complications as Measured by an Increase in AST &/or ALT ≥3-fold ULN & a CK ≥10-fold ULN | 3 months from baseline |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)
Ezetimibe: 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)- tablet, orally, 10mg/day for 12 weeks | 23 |
| Standard Care Increased dose of rosuvastatin to 20mg/day
Rosuvastatin (standard care): Increased dose of rosuvastatin to 20mg/day | 20 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Standard Care | Ezetimibe | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 23 Participants | 43 Participants |
| Age, Continuous | 57.0 Years STANDARD_DEVIATION 9.9 | 56.5 Years STANDARD_DEVIATION 7.4 | 57 Years STANDARD_DEVIATION 8.6 |
| Region of Enrollment Canada | 20 participants | 23 participants | 43 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 17 Participants | 22 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 20 |
| serious Total, serious adverse events | 0 / 23 | 0 / 20 |
Outcome results
Primary
The Primary Endpoint is the Difference in Final Value of Serum Apolipoprotein B Between Participants Treated With Rosuvastatin Versus Participants Treated With Both Rosuvastatin and Ezetimibe.
Time frame: 3 months from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | The Primary Endpoint is the Difference in Final Value of Serum Apolipoprotein B Between Participants Treated With Rosuvastatin Versus Participants Treated With Both Rosuvastatin and Ezetimibe. | 0.88 mmol/L | Standard Deviation 0.22 |
| Standard Care | The Primary Endpoint is the Difference in Final Value of Serum Apolipoprotein B Between Participants Treated With Rosuvastatin Versus Participants Treated With Both Rosuvastatin and Ezetimibe. | 0.89 mmol/L | Standard Deviation 0.25 |
Secondary
Assessment of Safety Parameters, Specifically Incidence of Complications as Measured by an Increase in AST &/or ALT ≥3-fold ULN & a CK ≥10-fold ULN
Time frame: 3 months from baseline
Secondary
Percent Change in Apolipoprotein B, Percent and Absolute Change Total Cholesterol, LDL, HDL, Triglycerides, Apolipoprotein A1, apolipoproteinB/apoliporoteinA1 Ratio and C-reactive Protein
Time frame: 3 months from baseline