Antiplatelet Therapy in HIV
|ClinicalTrials.gov Identifier: NCT02559414|
Recruitment Status : Completed
First Posted : September 24, 2015
Results First Posted : September 11, 2017
Last Update Posted : October 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|HIV Cardiovascular Diseases Inflammation||Drug: Aspirin Drug: Clopidogrel||Phase 2|
There is substantial evidence that the risk of serious non-AIDS conditions, such as cardiovascular disease, kidney disease, liver disease, and non-AIDS-defining malignancies, is increased in persons with HIV infection as compared to the general population. HIV-induced activation of inflammatory and coagulation pathways have been implicated in this increased risk. However, causative mechanisms linking HIV, inflammation, and increased risk of non-AIDS diseases are poorly described. The investigators are interested in studying the link between HIV induced inflammation and cardiovascular disease. Inflammation mediates many aspects of disease pathogenesis in atherosclerosis, involving diverse cell types and mediating signals. Specifically, platelets have been implicated in atherosclerosis because of their pro-inflammatory and thrombogenic effects. Moreover, clinical studies have demonstrated the importance of platelet activity in coronary artery atherosclerosis and thrombosis. Whereas there is a great understanding of the pathogenesis of cardiac disease, there is a wide knowledge gap in the understanding of mechanisms of cardiovascular disease in patients with HIV.
A recent study by the investigators demonstrated that platelet activity is heightened in subjects with HIV. Following 1-week of low-dose aspirin, platelet activity was inhibited. A surprising finding of this study demonstrated that antiplatelet therapy with 1 week of aspirin (325mg dose x1 day followed by 81mg daily) improved immune activity in subjects with HIV. The current study is being performed to replicate those findings when compared with a control group. Moreover, it remains unknown if the finding was specific to aspirin or whether the results were attributed to the antiplatelet effect of the drug. Clopidogrel is another antiplatelet therapy that targets the P2Y12 receptor (a different mechanism than aspirin) that has been shown to lower the risk of cardiovascular events in various clinical settings. The doses of aspirin and clopidogrel the investigators will be employing have been tested in hundreds of studies with well-known benefits and risks. The investigators believe that understanding the mechanistic role of platelet inhibitors in the setting of HIV will help uncover a new strategic pathway of HIV pathogenesis. Also, subjects with HIV are at increased risk for cardiovascular events and understanding the platelet inhibition of aspirin and clopidogrel will help establish better designs for future trials aimed at preventing these events in HIV infected persons.
The investigators have demonstrated that platelet activation is increased in HIV infection and can be attenuated by low-dose aspirin in a non-randomized study without a control group. Therefore, the Specific Aims of the study to be established are as follows:
- The effect of aspirin versus control on markers of platelet activity, inflammation, immune activity, and endothelial function.
- The effect of Clopidogrel versus control on markers of platelet activity, inflammation, immune activity, and endothelial function.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Antiplatelet Therapy in HIV - Antiplatelet and Immune Modulating Effects of Aspirin or Clopidogrel in Subjects With HIV|
|Actual Study Start Date :||February 2015|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||February 2017|
No Intervention: Control
This arm of 10 subjects will be assigned randomly via a computer generated treatment sequence, and then be given no antiplatelet medication.
Active Comparator: Aspirin
This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given aspirin.
Active Comparator: Clopidogrel
This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given clopidogrel.
- Percentage Platelet Aggregation in PRP After Stimulation With Arachidonic Acid 1600 μM for 5 Min [ Time Frame: Baseline, 14 Days ]The primary objective of these analyses will be to compare the effects of aspirin versus control and clopidogrel versus control for the outcome of platelet activity. Aspirin is expected to decrease arachidonic acid-induced platelet aggregation by 50% versus control. Clopidogrel is expected to decrease ADP-induced platelet aggregation by 50% versus control.
- Percentage Platelet Aggregation in PRP After Stimulation With ADP 5μM for 5 Min [ Time Frame: Baseline, 14 Days ]
- Percentage Monocyte-Platelet Aggregates [ Time Frame: 14 Days ]Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to inflammation
- Percentage Monocyte-Platelet Aggregates [ Time Frame: 14 Days ]Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to immune activity
- Percentage Leukocyte-Platelet Aggregate [ Time Frame: 14 Days ]Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to endothelial function.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02559414
|United States, New York|
|New York, New York, United States, 10016|
|NYU Langone Medical Center|
|New York, New York, United States, 10016|
|Principal Investigator:||Jeffrey S Berger, MD||NYU School of Medicine|