Effect of Atazanavir on Endothelial Function in HIV-Infected Patients
Information source: Foundation for Cardiovascular Research, Zurich
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Dyslipidemia
Intervention: ATAZANAVIR (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Foundation for Cardiovascular Research, Zurich Official(s) and/or principal investigator(s): Rainer Weber, Prof., Principal Investigator, Affiliation: University of Zurich
Summary
It is known that certain antiviral therapies, the socalled protease inhibitors, used in the
treatment of HIV infection has an untowarded effect on the blood vessels, promoting early
occurence of atherosclerosis. A a newer protease inhibitor, atazanavir, has been shown to
have no negative effect on the levels of blood cholesterol and it is hypothesized that this
may indicate that atazanavir is less prone to induce atherosclerosis. An early sign of
atherosclerosis is a reduced vasomotion and this study investigate the influence of
atazanavir on functionality of the conduit blood vessels compared to that of "standard"
antiviral therapy.
Clinical Details
Official title: Effect of Atazanavir on Endothelial Function in HIV-Infected Patients Compared to Standard Proteinase Inhibitors on Top of Potent Antiviral Combination Therapy
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Treatment
Primary outcome: Change of flow-mediated dilation in the forearm after 6 months using the protease inhibitor atazanavir in a potent antiviral therapy combination compared with a combination including current proteinase inhibitor.
Secondary outcome: Changes in plasma lipid profiles and further clinical chemistry parameters after 6 months of treatment compared to baseline.
Detailed description:
Indication: Dyslipidemia Type II in HIV-Infected Patients
Primary Objectives: Change of flow-mediated dilation in the forearm after 6 months using the
protease inhibitor atazanavir in a potent antiviral therapy combination compared with a
combination including current proteinase inhibitor.
Secondary Objectives: Changes in plasma lipid profiles and further clinical chemistry
parameters after 6 months of treatment compared to baseline.
Study Design: This is a multicenter, observer-blind (measurements of vessel parameters and
statistical evaluation), treatment-controlled, randomized, study with 2 treatment groups.
Planned Total Sample Size: (40-50) eligible randomized patients (20-25 per group) from 2-5
centers.
Subject Selection Criteria:
- Men and women, 18 to 65 years old.
- HIV-infection, documented by HIV-antibody ELISA and either positive immunoblot for
HIV-antibodies or presence of HIV1 in blood.
- Two consecutive Roche Ultrasensitive Amplicor tests showing plasma HIV-1 RNA < 50
copies/ml within 60 days prior to study entry.
- CD4 count of > 100 cells/ml during 60 days prior to study entry.
- Stable antiretroviral therapy for at least 12 weeks prior to study entry (a protease
inhibitor plus 2 NRTIs).
- Patient's treatment history allows, in the opinion of the investigator, atazanavir as
replacement for current PI, i. e. continued viral suppression is expected based upon
patient's treatment history and results of previous resistance testing, if available.
- Fasting LDL-cholesterol > 3. 0 mmol/l.
Contraindications for participation:
- Known coronary artery disease, hypertension, peripheral artery disease, or
cerebrovascular disease.
- Diabetes mellitus.
- Serious illness requiring systemic treatment and/or hospitalization within 14 days
prior to study entry.
- Any contraindication for study medication.
- Currently on non-nucleoside reverse transcriptase inhibitors (NNRTI) (previous exposure
allowed).
- Previous virologic failure on proteinase inhibitor-containing regimens which was not
the consequence of poor adherence to therapy or drug adverse events; i. e. virologic
failure was probably due to lack of potency of drug regimen, and may consecutively have
resulted in protease resistance mutations.
- Previously documented protease resistance mutations which are known to result in
cross-resistance against atazanavir.
- Any lipid lowering drugs within 4 weeks prior to study entry.
- Testosterone or anabolic steroids unless stable therapy at least 12 weeks prior to
study entry.
- Systemic glucocorticoids, long-acting inhaled steroids or other immunomodulators within
30 days prior to study entry (prednisone < 10mg/day or equivalent is permitted.
- Drug or alcohol abuse, in the opinion of the investigator rendering the patient
unreliable for participation.
- Participation in any other drug/treatment study.
Test Drugs:
1. Atazanavir capsules in daily standard dose (2 x 200 mg once daily) or
2. Continuation of current protease inhibitor
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Men and women, 18 to 65 years old.
- HIV-infection, documented by HIV-antibody ELISA and either positive immunoblot for
HIV-antibodies or presence of HIV1 in blood.
- Two consecutive Roche Ultrasensitive Amplicor tests showing plasma HIV-1 RNA < 50
copies/ml within 60 days prior to study entry.
- CD4 count of > 100 cells/ml during 60 days prior to study entry.
- Stable antiretroviral therapy for at least 12 weeks prior to study entry (a protease
inhibitor plus 2 NRTIs).
- Patient's treatment history allows, in the opinion of the investigator, atazanavir as
replacement for current PI, i. e. continued viral suppression is expected based upon
patient's treatment history and results of previous resistance testing, if available.
- Fasting LDL-cholesterol > 3. 0 mmol/l.
Exclusion Criteria:
- Known coronary artery disease, hypertension, peripheral artery disease, or
cerebrovascular disease.
- Diabetes mellitus.
- Serious illness requiring systemic treatment and/or hospitalization within 14 days
prior to study entry.
- Any contraindication for study medication.
- Currently on non-nucleoside reverse transcriptase inhibitors (NNRTI) (previous
exposure allowed).
- Previous virologic failure on proteinase inhibitor-containing regimens which was not
the consequence of poor adherence to therapy or drug adverse events; i. e. virologic
failure was probably due to lack of potency of drug regimen, and may consecutively
have resulted in protease resistance mutations.
- Previously documented protease resistance mutations which are known to result in
cross-resistance against atazanavir.
- Any lipid lowering drugs within 4 weeks prior to study entry.
- Testosterone or anabolic steroids unless stable therapy at least 12 weeks prior to
study entry.
- Systemic glucocorticoids, long-acting inhaled steroids or other immunomodulators
within 30 days prior to study entry (prednisone < 10mg/day or equivalent is
permitted.
- Drug or alcohol abuse, in the opinion of the investigator rendering the patient
unreliable for participation.
- Participation in any other drug/treatment study.
Locations and Contacts
University Hospital Zurich, Infectiology, Zurich, ZH 8091, Switzerland
Additional Information
Starting date: August 2004
Last updated: May 26, 2009
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