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

Sponsor

Azienda Ospedaliera di Perugia (Other)

Overall Status

Completed

CT.gov ID

NCT03316534

Collaborator

(none)

Enrollment

Arms

9.3

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-infected Patients	Drug: Aspirin	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

HIV subjects (all on ABC therapy) who fulfilled thee admission criteria will be randomized to either of 2 groups (A or B) with 20 subjects each that received placebo or aspirin (100 mg/daily) for two weeks. At the end of the two week period (T15), patients of group A will be switched to placebo, while group B will be switched to aspirin for another 2 weeks (T30). Adherence will be confirmed by pill count at the end of each study period.HIV subjects (all on ABC therapy) who fulfilled thee admission criteria will be randomized to either of 2 groups (A or B) with 20 subjects each that received placebo or aspirin (100 mg/daily) for two weeks. At the end of the two week period (T15), patients of group A will be switched to placebo, while group B will be switched to aspirin for another 2 weeks (T30). Adherence will be confirmed by pill count at the end of each study period.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Effect of Aspirin on Abacavir-induced Platelet Reactivity in HIV-infected Patients

Actual Study Start Date :

Jan 2, 2017

Actual Primary Completion Date :

Apr 30, 2017

Actual Study Completion Date :

Oct 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Drug: Aspirin Aspirin (100 mg once a day)
Active Comparator: Aspirin Aspirin (100 mg/daily)	Drug: Aspirin Aspirin (100 mg once a day)

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo

Drug: Aspirin

Aspirin (100 mg once a day)

Active Comparator: Aspirin

Aspirin (100 mg/daily)

Drug: Aspirin

Aspirin (100 mg once a day)

Outcome Measures

Primary Outcome Measures

Platelet reactivity [Change from baseline at day 15 and at day 30.]
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.

Secondary Outcome Measures

Serum TxB2 levels and urinary 11-dehydro-TxB2 levels [Change from baseline at day 14 after aspirin intake.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Azienda Ospedaliera di Perugia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Paolo Gresele, Full Professor, Internal Medicine, Azienda Ospedaliera di Perugia

ClinicalTrials.gov Identifier:

NCT03316534

Other Study ID Numbers:

1452/13/ACC

First Posted:

Oct 20, 2017

Last Update Posted:

Oct 20, 2017

Last Verified:

Oct 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Aspirin

Study Results

No Results Posted as of Oct 20, 2017