Tenofovir Abacavir Platelet Activation Study (TAPAS)

Changes in Coagulation and Platelet Reactivity in HIV-1 Infected Patients Switching Between Abacavir and Tenofovir Containing Antiretroviral Regimens

Some but not all observational studies have found that current exposure to abacavir is associated with increased risk of cardiovascular events such as myocardial infarction, stroke and cardiovascular death. This study aim to investigate possible adverse effect of abacavir on platelet reactivity, coagulation and endothelial activation in HIV-1 infected patients. The study is an open-labeled cross-over trial, where patients receiving antiretroviral therapy containing abacavir switch treatment to a regimen containing tenofovir and vice versa for a period of 90 days.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: abacavir (600 mg QD); Drug: tenofovir (245 mg QD)

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Copenhagen Ø, Copenhagen, Denmark, 2100
      • Rigshospitalet, Klinik for Infektionsmedicin og Reumatologi, 8622

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• HIV-1 infected
• Can understand and sign written informed consent
• Received one of the above mentioned antiretroviral regimens continuously ≥ 6 months
• HIV RNA < 400 copies/mL for ≥ 6 months

Exclusion Criteria:

• Receiving anticoagulant therapy, adenosine diphosphate (ADP) receptor inhibitors, aspirin or nonsteroidal antiinflammatory drugs (NSAIDs)
• Previous ischemic heart disease, peripheral atherosclerotic disease or stroke
• Coagulation disorder (e.g. hemophilia, factor V Leiden mutation)
• Platelet count < 150 x 109/L during the past 6 months from inclusion
• Estimated glomerular filtration rate (eGFR) <70 during the past 6 months from inclusion
• Humane leukocyte antigen (HLA)-B*57:01 positive genotype
• Hepatitis B or C positive during the past year from inclusion
• Hypersensitivity to the active substances or to any of the excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenofovir to abacavir; Patients switching from tenofovir (245 mg QD) to abacavir (600 mg QD)	Drug: abacavir (600 mg QD)
Experimental: Abacavir to tenofovir; Patients switching from abacavir (600 mg QD) to tenofovir (245 mg QD)	Drug: tenofovir (245 mg QD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differences in platelet aggregation (Multiplate) before and after switching between abacavir and tenofovir.	before and after 90 days intervention
Differences in clot formation kinetics (thromboelastography) before and after switching between abacavir and tenofovir.	before and after 90 days intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration of plasma lipids	Before and after 90 days intervention
activated partial thromboplastin time (APTT)	90 days
international normalized ratio (INR)/Factor II, VII, X	Before and after 90 days intervention
Platelet count	Before and after 90 days intervention
Fibrinogen	Before and after 90 days intervention
D-dimer	Before and after 90 days intervention
Antithrombine	Before and after 90 days intervention
Interleukin 6 (IL-6)	Before and after 90 days intervention
High sensitivity C reactive protein (HS-CRP)	Before and after 90 days intervention
Soluble P-Selectin	Before and after 90 days intervention
soluble CD40 ligand (sCD40L)	Before and after 90 days intervention
Syndecan-1	Before and after 90 days intervention
Soluble E-selectin	Before and after 90 days intervention
Tissue plasminogen activator	Before and after 90 days intervention

Collaborators and Investigators

• Sponsor: Jan Gerstoft
• Investigators: Principal Investigator: Jan Gerstoft, MD, DMSc, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 21, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: HIV-1; Abacavir; Platelet activation; Coagulation; Thromboelastography
• Additional Relevant MeSH Terms: 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; Tenofovir; Abacavir
• Other Study ID Numbers: 2013-001685-42