Cardiovascular Disease, HIV
Conditions
Keywords
HIV, Cardiovascular disease, Inflammation, Statin
Brief summary
This study is a randomised double blind placebo controlled trial comparing Rosuvastatin with placebo in HIV positive people who are at intermediate cardiovascular risk. It is possible that HIV positive people will receive a greater benefit from statins because of their higher baseline levels of inflammation. Current Australian guidelines recommend initiation of statin therapy on the basis of cholesterol level and the presence of other risk factors for heart disease (such as diabetes) but do not take into account whether a patient is infected with HIV. This study aims to determine what benefit HIV infected people will receive from starting statin therapy earlier then currently recommended.
Detailed description
Participants will be randomised to receive either the active agent (Rosuvastatin) or a placebo once daily for 96 weeks. Participants will undergo blood tests and ultrasounds of the arteries of the neck (carotid intima media thickness) prior to starting Rosuvastatin and then after 1 and 2 years on the drug to determine what effect it has on markers of inflammation, cholesterol levels and thickness of blood vessels.
Interventions
DRUGRosuvastatin
encapsulated tablet 20mg daily
OTHERPlacebo
Placebo arm included to maintain blinding
Sponsors
Bayside Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Moderate cardiovascular disease (CVD) risk, (10-15% 10 year risk of CVD) * HIV positive * Stable combination anti-retroviral therapy (cART) with plasma HIV viral load \<200copies/ml for ≥ 6 months
Exclusion criteria
* Recommended use of lipid lowering therapy according to Australian guidelines * Prior use of statin, fibrate, ezetimibe within the last six months * Contraindication to statin use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of Carotid Intima Media Thickness | Baseline to week 96 | Carotid intima media thickness will be measured by ultrasonography and the change from baseline to week 96 calculated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Adverse Events | Will be assessed every 12 weeks and formally reported at 96 weeks of followup | Number of participants with adverse events in total and also the number of participants with adverse events thought secondary to the study medication |
Countries
Australia, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received daily placebo | 40 |
| Active Participants received daily rosuvastatin | 44 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 6 |
Baseline characteristics
| Characteristic | Placebo | Active | Total |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 6.4 | 53.9 years STANDARD_DEVIATION 5.9 | 54.1 years STANDARD_DEVIATION 6.3 |
| Current cluster of differentiation of 4 (CD4) Cell count | 550 cells/ul STANDARD_DEVIATION 254 | 693 cells/ul STANDARD_DEVIATION 259 | 590 cells/ul STANDARD_DEVIATION 250 |
| Current Smoker | 12 Participants | 16 Participants | 28 Participants |
| Duration HIV infection | 13.6 years STANDARD_DEVIATION 7.7 | 17.2 years STANDARD_DEVIATION 8.5 | 16 years STANDARD_DEVIATION 7.9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Australia | 27 participants | 28 participants | 55 participants |
| Region of Enrollment Switzerland | 13 participants | 16 participants | 29 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 40 Participants | 42 Participants | 82 Participants |
| Total cholesterol | 5.3 mmol/L STANDARD_DEVIATION 1.1 | 5.4 mmol/L STANDARD_DEVIATION 0.8 | 5.3 mmol/L STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 1 / 44 |
| other Total, other adverse events | 29 / 40 | 36 / 44 |
| serious Total, serious adverse events | 6 / 40 | 7 / 44 |
Outcome results
Primary
Progression of Carotid Intima Media Thickness
Carotid intima media thickness will be measured by ultrasonography and the change from baseline to week 96 calculated
Time frame: Baseline to week 96
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Progression of Carotid Intima Media Thickness | 0.0062 mm | Standard Error 0.0039 |
| Rosuvastatin | Progression of Carotid Intima Media Thickness | 0.004 mm | Standard Error 0.0036 |
p-value: 0.684Mixed Models Analysis
Secondary
Rates of Adverse Events
Number of participants with adverse events in total and also the number of participants with adverse events thought secondary to the study medication
Time frame: Will be assessed every 12 weeks and formally reported at 96 weeks of followup
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Rates of Adverse Events | 22 Participants |
| Rosuvastatin | Rates of Adverse Events | 35 Participants |