Clinical trial NCT02093585: Tenofovir Abacavir Platelet Activation Study
Official title: Changes in Coagulation and Platelet Reactivity in HIV-1 Infected Patients Switching Between Abacavir and Tenofovir Containing Antiretroviral Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Keywords: HIV-1
Abacavir
Platelet activation
Thromboelastography
Coagulation
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2014-03-21
Enrollment: 43
Sex: MALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Differences in platelet aggregation (Multiplate) before and after switching between abacavir and tenofovir.
timeFrame: before and after 90 days intervention
measure: Differences in clot formation kinetics (thromboelastography) before and after switching between abacavir and tenofovir.
timeFrame: before and after 90 days intervention
Secondary outcomes:
measure: Concentration of plasma lipids
timeFrame: Before and after 90 days intervention
measure: activated partial thromboplastin time (APTT)
timeFrame: 90 days
measure: international normalized ratio (INR)/Factor II, VII, X
timeFrame: Before and after 90 days intervention
measure: Platelet count
timeFrame: Before and after 90 days intervention
measure: Fibrinogen
timeFrame: Before and after 90 days intervention
measure: D-dimer
timeFrame: Before and after 90 days intervention
measure: Antithrombine
timeFrame: Before and after 90 days intervention
measure: Interleukin 6 (IL-6)
timeFrame: Before and after 90 days intervention
measure: High sensitivity C reactive protein (HS-CRP)
timeFrame: Before and after 90 days intervention
measure: Soluble P-Selectin
timeFrame: Before and after 90 days intervention
measure: soluble CD40 ligand (sCD40L)
timeFrame: Before and after 90 days intervention
measure: Syndecan-1
timeFrame: Before and after 90 days intervention
measure: Soluble E-selectin
timeFrame: Before and after 90 days intervention
measure: Tissue plasminogen activator
timeFrame: Before and after 90 days intervention
Other outcomes:
Locations:
city: Copenhagen Ø
country: Denmark
facility: Rigshospitalet, Klinik for Infektionsmedicin og Reumatologi, 8622
state: Copenhagen
Study officials:
affiliation: Rigshospitalet, Denmark
name: Jan Gerstoft, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: