Effect of Atazanavir on Endothelial Function in HIV-Infected Patients (ENDOPACT)

May 26, 2009 updated by: Foundation for Cardiovascular Research, Zurich

Effect of Atazanavir on Endothelial Function in HIV-Infected Patients Compared to Standard Proteinase Inhibitors on Top of Potent Antiviral Combination Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • ZH
      • Zurich, ZH, Switzerland, 8091
        • University Hospital Zurich, Infectiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 Measures

Outcome Measure
Changes in plasma lipid profiles and further clinical chemistry parameters after 6 months of treatment compared to baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Foundation for Cardiovascular Research, Zurich

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Rainer Weber, Prof., University of Zurich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2004

Study Completion

May 1, 2006

Study Registration Dates

First Submitted

March 12, 2007

First Submitted That Met QC Criteria

March 13, 2007

First Posted (Estimate)

March 14, 2007

Study Record Updates

Last Update Posted (Estimate)

May 27, 2009

Last Update Submitted That Met QC Criteria

May 26, 2009

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICN 99034

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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