HIVPhase 2NCT02559414
Antiplatelet Therapy in HIV
A Phase 2 study testing Aspirin and Clopidogrel in people with HIV and Cardiovascular Diseases, run by NYU Langone Health at 2 sites in United States.
Trial summary
The proposed study will add to the growing understanding of platelet activity and platelet inhibition in subjects with HIV. It will examine the relationship between platelet activity and its inhibition by antiplatelet therapy (aspirin monotherapy and clopidogrel monotherapy) in this high-risk cohort. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- HIV, Cardiovascular Diseases, Inflammation
- What is being tested?
- Aspirin and Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2015to Feb 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infection
- Current Antiretroviral Therapy with no change in regimen in the 12 weeks prior to study entry and no plans to change ART for the study duration
- Ability to sign consent and comply with the protocol
Who cannot join
- Known CD4+ T cell counts < 200 cells/mm3 during the 6 months prior to study entry
- Established cardiovascular disease (thereby necessitating antiplatelet therapy)
- NSAID use in the past week (including aspirin)
- Unable to be off NSAIDs for the duration of the trial
- Any antiplatelet or antithrombotic use
- Allergy to aspirin or clopidogrel
Show all 14Show fewer
- Pregnancy
- Chronic kidney disease (GFR<45 ml/min)
- AIDS
- Active drug or alcohol use that would interfere with adherence to study requirements
- Any known bleeding disorder
- Use of regularly prescribed medication such as steroids, or immunosuppressive agents
- Known anemia (Hb <8mg/dL)
- Thrombocytopenia (platelet count <75) or thrombocytosis (Platelet count >600)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Bellevue Hospital
New York, New York, 10016
NYU Langone Medical Center
New York, New York, 10016
About this study
Official title: Antiplatelet Therapy in HIV - Antiplatelet and Immune Modulating Effects of Aspirin or Clopidogrel in Subjects With HIV
The proposed study will add to the growing understanding of platelet activity and platelet inhibition in subjects with HIV. It will examine the relationship between platelet activity and its inhibition by antiplatelet therapy (aspirin monotherapy and clopidogrel monotherapy) in this high-risk cohort. Furthermore, it will provide important data on the mechanism of platelet activity and its inhibition using biomarkers of platelet activity, inflammation, immune activity and endothelial function and genetic expression profiling.
Read the detailed description
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.
- Conditions
- HIV, Cardiovascular Diseases, Inflammation
- Being tested
- Aspirin, Clopidogrel
- Medical subject headings
- Cardiovascular Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
ClopidogrelDrug
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | This arm of 10 subjects will be assigned randomly via a computer generated treatment sequence, and then be given no antiplatelet medication. |
| Aspirin | Active comparator | This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given aspirin. Receives: Drug: Aspirin |
| Clopidogrel | Active comparator | This arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given clopidogrel. Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Platelet Aggregation in PRP After Stimulation With Arachidonic Acid 1600 μM for 5 Min
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.
Measured: Baseline, 14 Days
Secondary outcomes (4)
Percentage Platelet Aggregation in PRP After Stimulation With ADP 5μM for 5 Min
Measured: Baseline, 14 Days
Percentage Monocyte-Platelet Aggregates
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to inflammation
Measured: 14 Days
Percentage Monocyte-Platelet Aggregates
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to immune activity
Measured: 14 Days
Percentage Leukocyte-Platelet Aggregate
Secondary objectives will compare the effect of each antiplatelet therapy drug on biomarkers related to endothelial function.
Measured: 14 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2015 (estimated)
- Study startFeb 2015
- Primary completionApr 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey S Berger, MD, Principal investigator, NYU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02559414
- Sponsor's protocol ID
- 14-02104
- Status last verified
- Sep 2018
- First submitted
- 10 Mar 2015
- Last updated
- 15 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Berger JS, Lala A, Krantz MJ, Baker GS, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials. Am Heart J. 2011 Jul;162(1):115-24.e2. doi: 10.1016/j.ahj.2011.04.006.
PubMed 21742097Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006 Jan 18;295(3):306-13. doi: 10.1001/jama.295.3.306.
PubMed 16418466CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.
PubMed 8918275Solomon Tsegaye T, Gnirss K, Rahe-Meyer N, Kiene M, Kramer-Kuhl A, Behrens G, Munch J, Pohlmann S. Platelet activation suppresses HIV-1 infection of T cells. Retrovirology. 2013 May 1;10:48. doi: 10.1186/1742-4690-10-48.
PubMed 23634812Marcantoni E, Garshick MS, Schwartz T, Ratnapala N, Cambria M, Dann R, O'Brien M, Heguy A, Berger JS. Antiplatelet Effects of Clopidogrel Vs Aspirin in Virologically Controlled HIV: A Randomized Controlled Trial. JACC Basic Transl Sci. 2022 Oct 5;7(11):1086-1097. doi: 10.1016/j.jacbts.2022.06.002. eCollection 2022 Nov.
PubMed 36687270
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiplatelet Therapy in HIV - Antiplatelet and Immune Modulating Effects of Aspirin or Clopidogrel in Subjects With HIV
- ClinicalTrials.gov ID
- NCT02559414
- Acronym / sponsor ID
- 14-02104
- Conditions
- HIV, Cardiovascular Diseases, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Apr 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 24 Sep 2015 (estimated)
- Results
- Posted 11 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study will add to the growing understanding of platelet activity and platelet inhibition in subjects with HIV. It will examine the relationship between platelet activity and its inhibition by antiplatelet therapy (aspirin monotherapy and clopidogrel monotherapy) in this high-risk cohort. Furthermore, it will provide important data on the mechanism of platelet activity and its inhibition using biomarkers of platelet activity, inflammation, immune activity and endothelial function and genetic expression profiling.
Detailed description
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –This arm of 10 subjects will be assigned randomly via a computer generated treatment sequence, and then be given no antiplatelet medication. |
| Aspirin | Active comparator | Drug: AspirinThis arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given aspirin. |
| Clopidogrel | Active comparator | Drug: ClopidogrelThis arm of 20 subjects will be assigned randomly via a computer generated treatment sequence, and then be given clopidogrel. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HIV infection
- Current Antiretroviral Therapy with no change in regimen in the 12 weeks prior to study entry and no plans to change ART for the study duration
- Ability to sign consent and comply with the protocol
Key exclusion criteria (14 listed)
- Known CD4+ T cell counts < 200 cells/mm3 during the 6 months prior to study entry
- Established cardiovascular disease (thereby necessitating antiplatelet therapy)
- NSAID use in the past week (including aspirin)
- Unable to be off NSAIDs for the duration of the trial
- Any antiplatelet or antithrombotic use
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin | Drug | Aspirin |
| Clopidogrel | Drug | Clopidogrel |
Primary outcome
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.
4 secondary outcomes
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
Percentage Monocyte-Platelet Aggregates
Time frame: 14 Days
Percentage Leukocyte-Platelet Aggregate
Time frame: 14 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21742097Berger JS, Lala A, Krantz MJ, Baker GS, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials. Am Heart J. 2011 Jul;162(1):115-24.e2. doi: 10.1016/j.ahj.2011.04.006.
- Background: PubMed 16418466Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006 Jan 18;295(3):306-13. doi: 10.1001/jama.295.3.306.
- Background: PubMed 8918275CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.
- Background: PubMed 23634812Solomon Tsegaye T, Gnirss K, Rahe-Meyer N, Kiene M, Kramer-Kuhl A, Behrens G, Munch J, Pohlmann S. Platelet activation suppresses HIV-1 infection of T cells. Retrovirology. 2013 May 1;10:48. doi: 10.1186/1742-4690-10-48.
- Derived from this study: PubMed 36687270Marcantoni E, Garshick MS, Schwartz T, Ratnapala N, Cambria M, Dann R, O'Brien M, Heguy A, Berger JS. Antiplatelet Effects of Clopidogrel Vs Aspirin in Virologically Controlled HIV: A Randomized Controlled Trial. JACC Basic Transl Sci. 2022 Oct 5;7(11):1086-1097. doi: 10.1016/j.jacbts.2022.06.002. eCollection 2022 Nov.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey S Berger, MD principal investigator
NYU School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin and Clopidogrel in people with HIV and Cardiovascular Diseases, run by NYU Langone Health at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Platelet Aggregation in PRP After Stimulation With Arachidonic Acid 1600 μM for 5 Min (time frame: Baseline, 14 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02559414, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.