Atazanavir and Endothelial Function in Older HIV Patients

NCT03019783 | Completed Phase 2 Results

• 1 other identifier: AI424-469
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that older subjects with HIV randomly assigned to atazanavir will have increased bilirubin levels, reduced oxidative stress, and improved flow-mediated, endothelium-dependent vasodilation compared to subjects not switched to atazanavir.

Conditions

HIV

Keywords

Endothelial function

Outcome Measures

Primary Outcomes (1)

• Change in Flow-mediated, Endothelium-dependent Vasodilation

  The investigators will evaluate flow-mediated, brachial artery vasodilation (percentage increase in diameter in response to a 5 minute ischemic challenge) at study entry and then after 28 days, with the change between the two measurements being the primary endpoint.

  4 weeks

Secondary Outcomes (1)

• Change in Plasma Total Antioxidant Capacity

  4 weeks

Study Arms (2)

Remains on baseline HIV regimen

PLACEBO COMPARATOR

Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.

Other: Placebo

Atazanavir switch

ACTIVE COMPARATOR

These subjects are switched to an atazanavir-based regimen.

Drug: Atazanavir

Interventions

Atazanavir DRUG

The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.

Also known as: Reyataz

Atazanavir switch

Placebo OTHER

The control group will stay on their baseline regimen

Remains on baseline HIV regimen

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 45 years
• Stable non-atazanavir-containing regimen consisting of co-formulated tenofovir/emtricitabine as the NRTIs plus a third agent for 3 months or longer. The third agent can be any FDA-approved PI, NNRTI, or raltegravir.
• HIV RNA \< 200 cop/mL at screening and at least once within the prior year,
• No treatment interruptions \> 7 days in the 3 months prior to study entry
• The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
• Signed Written Informed Consent. Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug to minimize the risk of pregnancy.
• WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
• Amenorrhea that has lasted for 12 consecutive months without another cause, or
• For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
• Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product.

You may not qualify if:

• Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of study drug.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test.
• Target Disease Exceptions
• Prior treatment failure on or intolerance to atazanavir
• Known or suspected resistance to atazanavir
• Receiving ART different from co-formulated tenofovir/emtricitabine plus third agent (PI, NNRTI, or raltegravir) regimen
• Receiving Viagra, Levitra, or Cialis
• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Medical History and Concurrent Diseases
• Patients with Gilbert's Syndrome or elevated bilirubin levels (\>1.5 mg/dL) at baseline (for the randomized trial)
• Patients with uncontrolled diabetes (hemoglobin A1c \> 11%)
• Patients allergic to nitroglycerin

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Beckman JA, Wood BR, Ard KL, Price CN, Solomon DA, Zuflacht JP, Milian J, Prenner JC, Sax PE. Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir. PLoS One. 2017 Oct 12;12(10):e0181993. doi: 10.1371/journal.pone.0181993. eCollection 2017.

  PMID: 29023508 DERIVED

MeSH Terms

Interventions

Atazanavir Sulfate

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

There were no limitations.

Results Point of Contact

• Title: Dr. Joshua Beckman
• Organization: Brigham and Women's Hospital

joshua.a.beckman@vanderbilt.edu

617-732-5500

Study Officials

• Joshua Beckman

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 8, 2016
• First Posted: January 13, 2017
• Study Start: December 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: May 16, 2017
• Results First Posted: April 18, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)