Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study (SABAR)

• ClinicalTrials.gov Identifier: NCT00225017
• Recruitment Status: Completed
• First Posted: September 23, 2005
• Results First Posted: August 2, 2012
• Last Update Posted: August 2, 2012
• Sponsor: Northwestern University
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Robert L. Murphy, Northwestern University

Study Description

Brief Summary:

The purpose of this study is to evaluate the change in brachial artery reactivity in HIV-infected subjects with elevated lipid levels who are switched to an atazanavir containing antiretroviral regimen

Condition or disease	Intervention/treatment	Phase
HIV Infection; Hyperlipidemia	Drug: Atazanavir; Drug: current antiretroviral regimen	Phase 3

Detailed Description:

HIV-infected subjects on a stable protease inhibitor (PI) containing antiretroviral regimen with plasma HIV RNA <500 copies/mL, who have LDL cholesterol levels >130 mg/dL or fasting triglycerides levels >200 mg/dL, will be randomized (1:1) to continue their current antiretroviral regimen or to switch the PI to atazanavir (ATV). Brachial artery reactivity will be measured before (at entry) and 12 and 24 weeks after subjects are randomized.

ARM A: Switch current PI to atazanavir 400 mg once daily plus current > 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 24 weeks.

Subjects currently on ritonavir (RTV) (400 mg BID or greater) or RTV-boosted PI (<400 mg/day) , or tenofovir (TDF) as backbone NRTI therapy, will switch to ATV 300 mg boosted with RTV 100mg once daily.

ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus > 2 NRTIs) for 24 weeks

Brachial artery reactivity in response to two vasoactive stimuli (increased forearm blood flow and nitroglycerin) will be assessed by measuring brachial artery diameter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Switch to Atazanavir and Brachial Artery Reactivity (SABAR) Study: Endothelial Function in HIV-Infected Subjects Switched to an Atazanavir Regimen
• Study Start Date: June 2005
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; ARM A: Switch current PI to atazanavir 400 mg once daily plus current > 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 24 weeks. Subjects currently on ritonavir (RTV) (400 mg BID or greater) or RTV-boosted PI (<400 mg/day) , or tenofovir (TDF) as backbone NRTI therapy, will switch to ATV 300 mg boosted with RTV 100mg once daily.	Drug: Atazanavir; atazanavir 400 mg once daily; Other Name: Reyataz
Active Comparator: B; ARM B: Continue current antiretroviral regimen (single or RTV-boosted PI plus > 2 NRTIs) for 24 weeks	Drug: current antiretroviral regimen; Continue current antiretroviral regimen for 24 weeks, single or RTV-boosted PI plus > 2 NRTIs

Outcome Measures

Primary Outcome Measures :

1. Percentage Change in Brachial Artery Flow Mediated (FMD) Vasodilation Between Arms From Baseline to Week 24 [ Time Frame: Baseline to week 24 ]
   Brachial artery reactivity assessed by noninvasively measuring brachial artery diameter and flow velocities in response to overinflated blood pressure cuff (Flow mediated dilation (FMD))in subjects switching to atazanavir and in subjects continuing on a stable antiretroviral regimen

Secondary Outcome Measures :

1. Change in Total Cholesterol Levels From Baseline to Week 24 [ Time Frame: Baseline to 24 weeks ]
   Total cholesterol level changes within and between arms
2. Changes in LDL Particle Number From Baseline to Week 24 [ Time Frame: Baseline to 24 weeks ]
   Change in LDL particle number

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• HIV infection
• HIV-1 RNA < 500 copies/ml
• Fasting LDL cholesterol >130 mg/dl OR fasting triglycerides >200 mg/dl
• CD4 count >100 cells/mm
• Stable antiretroviral regimen for at least 12 weeks prior to study entry that includes a protease inhibitor (PI) with or without ritonavir boosting

Exclusion Criteria:

• History of heart disease, uncontrolled hypertension, peripheral vascular disease
• Current non-nucleoside reverse transcriptase inhibitor (NNRTI) in the PI-containing regimen within 4 weeks
• Prior or current use of atazanavir
• Initiation of treatment with lipid-lowering drugs within 4 weeks prior to study entry

Contacts and Locations

Locations

United States, California

University of California

San Diego, California, United States, 92103

United States, Illinois

Northwestern Universtiy

Chicago, Illinois, United States, 60611

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Argentina

ACLIRES - Argentina S.R.L.

Buenos Aires, Argentina

Italy

Universita degli studi di Modena e Reggio Emilia

Modena, Italy

Sponsors and Collaborators

Northwestern University

Bristol-Myers Squibb

Investigators

• Study Chair: Robert L Murphy, MD; Northwestern University
• Study Chair: James H Stein, MD; University of Wisconsin, Madison

More Information

Publications of Results:

Murphy RL, Berzins B, Zala C, Fichtenbaum C, Dube MP, Guaraldi G, Torriani F, Belsey E, Mitchell C, Stein JH; SABAR Study Team. Change to atazanavir/ritonavir treatment improves lipids but not endothelial function in patients on stable antiretroviral therapy. AIDS. 2010 Mar 27;24(6):885-90. doi: 10.1097/QAD.0b013e3283352ed5.

• Responsible Party: Robert L. Murphy, Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00225017
• Other Study ID Numbers: SABAR
• First Posted: September 23, 2005
• Results First Posted: August 2, 2012
• Last Update Posted: August 2, 2012
• Last Verified: June 2012

Keywords provided by Robert L. Murphy, Northwestern University:

Atazanavir; Endothelial function; Treatment Experienced

Additional relevant MeSH terms:

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Atazanavir Sulfate; Anti-Retroviral Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Antiviral Agents; Anti-Infective Agents