Cardiovascular Disease Risk in HIV PatientsPhase 1/2MHEARTNCT02401269
Cardiovascular Risk in HIV Patients on Antiretroviral Therapy Therapy: The MHEART Study
A Phase 1/2 study testing Aspirin in people with Cardiovascular Disease Risk in HIV Patients and Endothelial Function, run by University of Pittsburgh at 1 site in Malawi.
Trial summary
CVD accounts for 15% of all deaths in Malawi. Both HIV and ART are risk factors for CVD through direct toxic and inflammatory cardiovascular effects. (44,45). At the moment, one out of every 10 Malawian is HIV positive and roughly 8 out of 10 of those infected are now on ART (2). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cardiovascular Disease Risk in HIV Patients, Endothelial Function
- What is being tested?
- Aspirin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteMalawi
- Study dates
- Apr 2015to Jan 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Malawian men and women ages 18-70 who are HIV positive and on ART for at least 6 months on standard therapy (1st line, 2nd line or 3rd line). The HIV viral load at time of enrollment must be suppressed confirmed by HIV DNA PCR in the last 60 days.
Who cannot join
- All patients with risk factors that result in endothelial dysfunction and atherosclerosis will be excluded based on the following exclusion criteria. The rationale behind this is to isolate the effects of virally suppressed HIV on endothelial activity.
- Presence of HIV viral load in the last 60 days
- History of diagnosed Diabetes Mellitus
- Fasting blood sugar >110 at time of enrollment determined by glucose on chemistry profile
- Uncontrolled Hypertension defined as systolic blood pressure > or equal to 140 and or diastolic >100 mmHg at time of enrollment
- AST or ALT >200 within the last 30 days. If not obtained in this interval, a baseline AST/ALT will be obtained
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- Renal Failure at time of recruitment (Gfr. <60ml/min/1.73) based on Cockcroft Gault equation.
- History of myocardial infarction, peripheral vascular disease, cerebrovascular disease. These will also be assessed clinically at the time of enrollment
- Health condition that would place patient at a health risk for perfusion ischemia during EndoPAT, FMD, CIMT measurement.
- Current tobacco use or history of tobacco use in the last 90 days
- Platelet count less than 100 at time of enrollment
- History of active brain mass/lesion
- Gastrointestinal bleeding in last 12 months
- History of hemorrhagic stroke
- Major life threatening bleeding in the last 12 months
- Patients considered to be a high bleed risk based on physician assessment
- History of medication noncompliance in last 3 months
- Pregnancy
- Contraindications to aspirin
- Previous allergic reaction to aspirin or similar medications to aspirin
- Asthma with nasal congestion or nasal polyps
- Bleeding disorders (inherited or acquired)
- Chicken pox
Trial locations and contacts
1 site in 1 country.
About this study
CVD accounts for 15% of all deaths in Malawi. Both HIV and ART are risk factors for CVD through direct toxic and inflammatory cardiovascular effects. (44,45). At the moment, one out of every 10 Malawian is HIV positive and roughly 8 out of 10 of those infected are now on ART (2). Therefore, HIV and ART may be contributing to the burden of CVD in Malawi. Currently, there are only a few studies assessing CVD risk in the HIV patient population on ART. In Malawi, no such studies exist. Therefore, the investigators propose a novel study assessing baseline cardiovascular disease risk using two novel ultrasound technologies in HIV patients on ART. Cardiovascular disease risk will be assessed using surrogate cardiovascular markers of disease. These surrogates include markers of endothelial function and cardiovascular modulating inflammatory biomarkers. The inflammatory biomarkers measured will be TNF-alpha, IL-6, and CRP. Aspirin, by way of its antiplatelet and anti-inflammatory effect has been demonstrated to inhibit atherosclerosis by way of decreasing TNF-alpha, IL-6, CRP and improving endothelial function. Therefore a second aim of the study will be to demonstrate that aspirin improves surrogate markers of atherosclerosis.
Read the detailed description
To address our objectives we have designed a six-month prospective randomized controlled study (RCT) investigating cardiovascular disease risk in HIV patients on ART with the implementation of an aspirin versus placebo strategy to investigate whether this risk can be modified. As nearly all HIV patients are anticipated to be on ART in the upcoming decade, we have decided to open this study to only virally suppressed HIV on ART. A total of 100 virally suppressed HIV positive Malawians on ART will be enrolled in this study. Initial screening will occur in the patient population identified as being HIV positive with viral load suppression on ART in the last 3 months. The initial screening will provide cross-sectional information on baseline demographic, clinical, and laboratory characteristics of virally suppressed HIV patients on ART and will assess baseline cardiovascular risk using laboratory biomarker data and endothelial function as surrogate markers (see section under procedures). Ability of distal arteries to dilate under stress will be measured using novel ultrasound technologies applicable to the limited resource healthcare settings in Malawi. After initial screening, eligibility into the study will be determined and selected participants will be randomized into one of two arms:
- Oral aspirin 325mg daily
- Oral placebo daily.
This longitudinal RCT will reassess cardiovascular risk at the one-month, 3-month, and six-month mark using the same CVD surrogate measurements of atherosclerosis performed during the initial screening.
Procedures assessing surrogate CVD markers for atherosclerosis:
- Laboratory analysis (Venipuncture): Inflammatory biomarkers
- C-Reactive Protein (CRP), Interleukin-6, Tumor Necrosis Factor- alpha
- Endo-PAT analysis
- Brachial Flow Mediated dilation
- Carotid Intima-Media Thickness
- Being tested
- Aspirin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Aspirin | Experimental | Aspirin 325mg daily Receives: Drug: Aspirin |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reactive Hyperemia Index
Assessment of peripheral arterial endothelial function
Measured: Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment
Quantification of inflammatory biomarkers- TNF-alpha, C-Reactive Protein, Interleukin-6
Assessment of biochemical surrogates of cardiovascular disease
Measured: Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment.
Secondary outcomes (2)
Bleeding
Measured: 30 days, 60 days, 90 days.
Hemoglobin
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study startApr 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular Disease Risk in HIV PatientsStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Fogarty International Center of the National Institute of Health, University of North Carolina
- Responsible party
- Principal investigator, Anil Purohit, MD, University of Pittsburgh
- Investigators
- Anil Purohit, M.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02401269
- Sponsor's protocol ID
- PRO14040373
- Acronym
- MHEART
- Status last verified
- Jan 2016
- First submitted
- 24 Mar 2015
- Last updated
- 15 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Risk in HIV Patients on Antiretroviral Therapy Therapy: The MHEART Study
- ClinicalTrials.gov ID
- NCT02401269
- Acronym / sponsor ID
- MHEART / PRO14040373
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Fogarty International Center of the National Institute of Health, University of North Carolina
- Study start
- Apr 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 27 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CVD accounts for 15% of all deaths in Malawi. Both HIV and ART are risk factors for CVD through direct toxic and inflammatory cardiovascular effects. (44,45). At the moment, one out of every 10 Malawian is HIV positive and roughly 8 out of 10 of those infected are now on ART (2). Therefore, HIV and ART may be contributing to the burden of CVD in Malawi. Currently, there are only a few studies assessing CVD risk in the HIV patient population on ART. In Malawi, no such studies exist. Therefore, the investigators propose a novel study assessing baseline cardiovascular disease risk using two novel ultrasound technologies in HIV patients on ART. Cardiovascular disease risk will be assessed using surrogate cardiovascular markers of disease. These surrogates include markers of endothelial function and cardiovascular modulating inflammatory biomarkers. The inflammatory biomarkers measured will be TNF-alpha, IL-6, and CRP. Aspirin, by way of its antiplatelet and anti-inflammatory effect has been demonstrated to inhibit atherosclerosis by way of decreasing TNF-alpha, IL-6, CRP and improving endothelial function. Therefore a second aim of the study will be to demonstrate that aspirin improves surrogate markers of atherosclerosis.
Detailed description
To address our objectives we have designed a six-month prospective randomized controlled study (RCT) investigating cardiovascular disease risk in HIV patients on ART with the implementation of an aspirin versus placebo strategy to investigate whether this risk can be modified. As nearly all HIV patients are anticipated to be on ART in the upcoming decade, we have decided to open this study to only virally suppressed HIV on ART. A total of 100 virally suppressed HIV positive Malawians on ART will be enrolled in this study. Initial screening will occur in the patient population identified as being HIV positive with viral load suppression on ART in the last 3 months. The initial screening will provide cross-sectional information on baseline demographic, clinical, and laboratory characteristics of virally suppressed HIV patients on ART and will assess baseline cardiovascular risk using laboratory biomarker data and endothelial function as surrogate markers (see section under procedures). Ability of distal arteries to dilate under stress will be measured using novel ultrasound technologies applicable to the limited resource healthcare settings in Malawi. After initial screening, eligibility into the study will be determined and selected participants will be randomized into one of two arms:
- Oral aspirin 325mg daily
- Oral placebo daily.
This longitudinal RCT will reassess cardiovascular risk at the one-month, 3-month, and six-month mark using the same CVD surrogate measurements of atherosclerosis performed during the initial screening.
Procedures assessing surrogate CVD markers for atherosclerosis:
- Laboratory analysis (Venipuncture): Inflammatory biomarkers
- C-Reactive Protein (CRP), Interleukin-6, Tumor Necrosis Factor- alpha
- Endo-PAT analysis
- Brachial Flow Mediated dilation
- Carotid Intima-Media Thickness
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aspirin | Experimental | Drug: AspirinAspirin 325mg daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Malawian men and women ages 18-70 who are HIV positive and on ART for at least 6 months on standard therapy (1st line, 2nd line or 3rd line). The HIV viral load at time of enrollment must be suppressed confirmed by HIV DNA PCR in the last 60 days.
Key exclusion criteria (23 listed)
- All patients with risk factors that result in endothelial dysfunction and atherosclerosis will be excluded based on the following exclusion criteria. The rationale behind this is to isolate the effects of virally suppressed HIV on endothelial activity.
- Presence of HIV viral load in the last 60 days
- History of diagnosed Diabetes Mellitus
- Fasting blood sugar >110 at time of enrollment determined by glucose on chemistry profile
- Uncontrolled Hypertension defined as systolic blood pressure > or equal to 140 and or diastolic >100 mmHg at time of enrollment
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 |
| Placebo | Drug | Placebo |
Primary outcome
Reactive Hyperemia Index
Time frame: Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment
Assessment of peripheral arterial endothelial function
Quantification of inflammatory biomarkers- TNF-alpha, C-Reactive Protein, Interleukin-6
Time frame: Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment.
Assessment of biochemical surrogates of cardiovascular disease
2 secondary outcomes
Bleeding
Time frame: 30 days, 60 days, 90 days.
Hemoglobin
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2016.
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HIV, Hypertension
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.
Anil Purohit, M.D. principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Aspirin in people with Cardiovascular Disease Risk in HIV Patients and Endothelial Function, run by University of Pittsburgh at 1 site in Malawi.
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 1 inclusion and 23 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 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Reactive Hyperemia Index (time frame: Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jan 2016.