Cardiovascular Risk in HIV Patients on Antiretroviral Therapy Therapy: The MHEART Study

Endothelial Function Clinical Trial

— MHEART  

Official title:

Cardiovascular Risk in HIV Patients on Antiretroviral Therapy Therapy: The MHEART Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02401269
• Other study ID #: PRO14040373
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 24, 2015
• Last updated: January 13, 2016
• Start date: April 2015
• Est. completion date: January 2016

Study information

• Verified date: January 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardMalawi: Institutional Review Board
• Study type: Interventional

Clinical 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). 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.

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:

1. Oral aspirin 325mg daily

2. 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:

1. Laboratory analysis (Venipuncture): Inflammatory biomarkers

• C-Reactive Protein (CRP), Interleukin-6, Tumor Necrosis Factor- alpha

2. Endo-PAT analysis

3. Brachial Flow Mediated dilation

4. Carotid Intima-Media Thickness

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

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.

1. Presence of HIV viral load in the last 60 days

2. History of diagnosed Diabetes Mellitus

3. Fasting blood sugar >110 at time of enrollment determined by glucose on chemistry profile

4. Uncontrolled Hypertension defined as systolic blood pressure > or equal to 140 and or diastolic >100 mmHg at time of enrollment

5. AST or ALT >200 within the last 30 days. If not obtained in this interval, a baseline AST/ALT will be obtained

6. Renal Failure at time of recruitment (Gfr. <60ml/min/1.73) based on Cockcroft Gault equation.

7. History of myocardial infarction, peripheral vascular disease, cerebrovascular disease. These will also be assessed clinically at the time of enrollment

8. Health condition that would place patient at a health risk for perfusion ischemia during EndoPAT, FMD, CIMT measurement.

9. Current tobacco use or history of tobacco use in the last 90 days

10. Platelet count less than 100 at time of enrollment

11. History of active brain mass/lesion

12. Gastrointestinal bleeding in last 12 months

13. History of hemorrhagic stroke

14. Major life threatening bleeding in the last 12 months

15. Patients considered to be a high bleed risk based on physician assessment

16. History of medication noncompliance in last 3 months

17. Pregnancy

18. 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease Risk in HIV Patients
• Cardiovascular Diseases
• Endothelial Function

Intervention

Drug:
• Aspirin

• Placebo

Locations

Country	Name	City	State
Malawi	Lighthouse Trust	Lilongwe

Sponsors (3)

Lead Sponsor	Collaborator
University of Pittsburgh	John E. Fogarty International Center (FIC), University of North Carolina

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reactive Hyperemia Index	Assessment of peripheral arterial endothelial function	Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment	No
Primary	Quantification of inflammatory biomarkers- TNF-alpha, C-Reactive Protein, Interleukin-6	Assessment of biochemical surrogates of cardiovascular disease	Baseline, 30 days after treatment, 60 days after treatment, 90 days after treatment.	No
Secondary	Bleeding		30 days, 60 days, 90 days.	Yes
Secondary	Hemoglobin		6 months	Yes