Determining the Effect of Abacavir on Platelet Activation

Determining the Effect of Abacavir on Platelet Activation in Virologically Suppressed HIV Positive Men: an Open Label Interventional Study

HIV positive patients have a two fold increased risk of developing cardiovascular disease (such as heart attacks and strokes). Cardiovascular disease appears to be due in part to both HIV and the side effects from anti-HIV medications.

Abacavir (an important component of current HIV treatment regimens) is one medication shown to be associated with an increase the risk of heart attacks in some studies. The mechanism by which abacavir does this is unknown.

We hypothesise that abacavir is leading to heart disease by interacting with platelets, which then form blood clots within the arteries supplying the heart, the subsequent blockage of the artery causing a heart attack.

This study aims to determine if abacavir increases the activity (or "stickiness") of platelets, and thus provide evidence as to how it may be promoting heart attacks.

It will consist of 23 HIV positive men who currently have well controlled HIV. Participants will take abacavir for 15 days in addition to their usual anti-HIV medications. A blood sample to assess platelet activity will be taken at baseline, following the 15 days of therapy (i.e. at the time of maximal abacavir effect) and again after a 28 day washout period (to determine if any effects are reversible).

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; HIV
• Intervention / Treatment: Drug: Abacavir

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• > 18 years of age
• Male
• HIV positive
• Stable non-abacavir containing anti-retroviral regimen
• Undetectable HIV Viral load

Exclusion Criteria:

• HLA-B*57*01 allele positivity
• Previous allergy to abacavir
• Known cardiovascular disease
• High Baseline cardiovascular risk (Framingham risk score > 20%)
• Current or recent antiplatelet therapy
• Pre-existing platelet or bleeding disorder (i.e. Thrombophilia, Thrombocytopenia, Von willebrands disease, Haemophilia)
• Significant Chronic liver disease
• Current Methadone use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Abacavir; Abacavir 600mg (as two 300mg tablets) once daily for 15 days	Drug: Abacavir; Other Names: Ziagen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Phosphorylated Vasodilator Stimulated Phosphoprotein (P-VASP) assay	Baseline, day 15 and day 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet aggregation	Measurement of the degree of platelet aggregation in response to collagen related peptide and thrombin receptor-agonist peptide	Baseline, Day 15 and day 48
Platelet specific collagen receptor glycoprotein VI (GPVI)	Measurement of the expression and shedding of platelet specific collagen receptor GPVI	Baseline, Day 15 and Day 48

Collaborators and Investigators

• Sponsor: Bayside Health
• Investigators: Principal Investigator: Jennifer Hoy, MBBS FRACP, Alfred health, Monash University; Principal Investigator: Janine Trevillyan, MBBS FRACP, Alfred health, Monash University

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (ESTIMATE): June 26, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): May 22, 2015
• Last Update Submitted That Met QC Criteria: May 21, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Cardiovascular disease; HIV; Platelets; Abacavir; Acute myocardial infarction; Antiretrovirals
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Abacavir
• Other Study ID Numbers: 248-13; ACTRN12613000570785 (REGISTRY: ANZCTR)