Effect of Aspirin on Abacavir-induced Platelet Reactivity in HIV-infected Patients (ABC-ASA)

The specific research questions addressed in the present study are:

• to investigate the impact of treatment with low-dose aspirin in HIV-1-infected patients treated with ABC and test it would result in decreased in vivo platelet activation and platelet hyperreactivity
• to investigate if aspirin has the same effects in HIV-infected as in HIV-uninfected patients.

Study Overview

• Status: Completed
• Conditions: HIV-infected Patients
• Intervention / Treatment: Drug: Aspirin

Detailed Description

Highly active antiretroviral therapy (HAART) may reduce the deleterious effects of HIV on the cardiovascular system by decreasing viral load and chronic inflammation; however some antiretrovirals enhance cardiovascular risk due to direct adverse effects on platelets or the endothelium.

Abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) are the most widely used nucleoside reverse transcriptase inhibitor (NRTI) associations in HAART. ABC has been initially considered as one of the most benign antiretroviral drugs due to a better metabolic profile than other nucleoside analogues, but since the D.A.D. study reported an association between the use of ABC and an increase in cardiovascular risk there has been controversy around this drug.

Clinical evidence suggests that in vivo platelet activation and platelet hyperreactivity contribute to adverse cardiovascular events and hyperreactive platelets may transform a normal reparative response to a mild arterial injury into an unwanted thrombotic event.

Aspirin is the cornerstone in the prevention of atherothrombotic events, as it has been shown to be effective both in the primary and secondary prevention of MI (6), and its beneficial effects likely involve the modulation of inflammatory and immune pathways. But despite heightened awareness regarding elevated CVD risk among HIV-infected patients, aspirin or others antiplatelet therapy were markedly underprescribed among HIV-infected patients at risk for CVD events (7).

Based on this, the proposed study will assess whether low-dose aspirin, in well-characterized HIV-1-infected patients treated with ABC, would result in decreased in vivo platelet activation and platelet hyperreactivity. Moreover will be investigate if aspirin will have the same effects in HIV-infected as in HIV-uninfected patients.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a viral load <50 copies per millilitre
• ABC treatment for at least 6 months

Exclusion Criteria:

• age younger than 18
• nonsteroidal anti-inflammatory drug use in the past week (including aspirin), renal failure (creatinine clearance <30 mL/min), platelet count <100,000/microL, history of gastrointestinal bleeding within the last 6 months, presence of coexisting inflammatory disease, cancer, active bacterial or fungal infection, bleeding history, oral anticoagulant therapy and allergy to aspirin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Aspirin; Aspirin (100 mg once a day)
ACTIVE_COMPARATOR: Aspirin; Aspirin (100 mg/daily)	Drug: Aspirin; Aspirin (100 mg once a day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	PFA-100® collagen/epinephrine (C/EPI) cartridge closure time; light transmission aggregometry induced by arachidonic acid (1mM), collagen (0.8, 1.2 and 2 microg/ml) and epinephrine (100 microM); PAC-1; soluble P-selectin; sCD40L; platelet microparticles detection and quantification.	Change from baseline at day 15 and at day 30.

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum TxB2 levels and urinary 11-dehydro-TxB2 levels	Change from baseline at day 14 after aspirin intake.

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Perugia

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2017
• Primary Completion (ACTUAL): April 30, 2017
• Study Completion (ACTUAL): October 12, 2017

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: October 17, 2017
• First Posted (ACTUAL): October 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 20, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 1452/13/ACC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No