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| Name | Class |
|---|---|
| Merck Frosst-Schering Pharma, G.P. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ezetimibe | Active Comparator | 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day) |
|
| Standard Care | Active Comparator | Increased dose of rosuvastatin to 20mg/day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ezetimibe | Drug | 10mg/day ezetimibe in addition to ongoing rosuvastatin treatment (10mg/day)- tablet, orally, 10mg/day for 12 weeks |
|
| Measure | Description | 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 |
| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Greg Bondy, MD | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Paul's Hospital HIV Immunodeficiency/Metabolic Clinic | Vancouver | British Columbia | V6Z 1Y6 | Canada |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Standard Care |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Rosuvastatin (standard care) | Drug | Increased dose of rosuvastatin to 20mg/day |
|
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| 3 months from baseline |
Increased dose of rosuvastatin to 20mg/day Rosuvastatin (standard care): Increased dose of rosuvastatin to 20mg/day |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Standard Care | Increased dose of rosuvastatin to 20mg/day Rosuvastatin (standard care): Increased dose of rosuvastatin to 20mg/day |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | mmol/L | 3 months from baseline |
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| ||||||||||||||||||||||||||||||
| Secondary | Percent Change in Apolipoprotein B, Percent and Absolute Change Total Cholesterol, LDL, HDL, Triglycerides, Apolipoprotein A1, apolipoproteinB/apoliporoteinA1 Ratio and C-reactive Protein | Not Posted | 3 months from baseline | ||||||||||||||||||||||||||||||||||||
| 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 | Not Posted | 3 months from baseline |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 23 | 0 | 23 | ||
| EG001 | Standard Care | Increased dose of rosuvastatin to 20mg/day Rosuvastatin (standard care): Increased dose of rosuvastatin to 20mg/day | 0 | 20 | 0 | 20 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Greg Bondy | St. Paul's Hospital/University of B.C. | 604-806-8192 | gbondy@providencehealth.bc.ca |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069438 | Ezetimibe |
| D000068718 | Rosuvastatin Calcium |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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| >=65 years |
|
| Male |
|