Clinical trial NCT03986697: How Does Antiretroviral Therapy Affect Coronary Atherosclerosis: a Serial CT Study
Official title: In Patients Taking Protease Inhibitors Does Switching to a Bictegravir, Tenofovir Alafenamide and Emtricitabine Combination, Reduce Cardiovascular Risk: an Open-label, Randomised, Serial CT Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Hiv
Keywords: HIV
Coronary Artery Disease
Atherosclerosis
Antiretroviral therapy
Computed tomography
Lead sponsor: University of Liverpool
Sponsor class: OTHER
First posted: 2019-06-14
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Combined antiretroviral therapy (cART) is thought to promote coronary artery disease via a number of mechanisms: abnormal lipid profiles, endothelial dysfunction, hypertension, insulin resistance and renal impairment are the main pathological mechanisms driving atherosclerosis as a consequence of cART. An association between protease inhibitors and increased cardiovascular disease risk has been shown in many large cohort trials.

CT Coronary Angiography (CTCA) is now widely used to assess for the presence of atherosclerosis, typically in patients presenting with chest pain. This imaging technique allows visualisation of the coronary arteries and quantification of any atherosclerotic disease that may be present. This technique is being increasingly used as a surrogate for cardiovascular disease risk.

HART CT is an open label, prospective, randomised-control pilot study to investigate the feasibility of performing a future appropriately powered multi-centred randomised control trial using CT based outcome data as a surrogate for cardiovascular disease risk.

Participants will be randomised to either continue their usual cART or switch to Biktarvy (a fixed dose combination of bictegravir, emtricitabine and tenofovir alafenamide). A baseline CT scan will be performed. If there is any evidence of atherosclerosis a further CT scan will be performed at the end of the study (approximately 48 weeks). This will allow quantification of any change in coronary artery plaque burden or characteristic. Participants will be also followed up for any changes in metabolic health.


Eligibility criteria: * HIV positive
* Undetectable viral load on cART which contain protease inhibitors (duration \>6 months at eligibility visit)
* Age\>40 years
* Stable cART
* No previous documented cardiovascular disease
* No contraindication to study drug
* Ability to give informed consent
* Willingness to comply with all study requirements
* No symptoms of overt cardiovascular disease

A definition of stable cART is no change to the medication regime in the preceding 6 months.

Well controlled hypertension is considered acceptable for recruitment.

Exclusion Criteria:

* Active liver disease (previously diagnosed)
* Renal disease eGFR \<30
* Any ongoing infection
* Significant ionising radiation in preceding 12 months
* Known or suspected cardiovascular disease
* High dose statin therapy (Atorvastatin 20mg or more, Rosuvastatin 20mg or more)
* Pregnancy or planned pregnancy
* Breast feeding
* Allergy to iodine based contrast agent
* Known drug resistance to NRTI or Integrase
* Any contraindication to BIC/FTC/TAF
* Current enrolment onto another CTIMP.

Significant ionising radiation should not exceed \>25mSv from medical sources. A definition of cardiovascular disease includes documented angina, previous myocardial infarction or previous coronary revascularization.

Primary outcomes:
measure: The rate of recruitment to the HART CT study
timeFrame: 2 years
measure: Drop out rate
timeFrame: 2 years
measure: Change in total plaque volume (mm3) including the following derivatives: total non-calcified plaque volume (mm3), calcium volume (mm3). These derivatives will be combined to give a total plaque volume (mm3).
timeFrame: 2 years
measure: Change in Agatston Score (Agatston units).
timeFrame: 2 years
measure: Change in segmental stenosis score
timeFrame: 2 years
measure: Number of adverse plaque features
timeFrame: 2 years
Secondary outcomes:
measure: Inter and intraobserver variability of CT based outcome measures
timeFrame: 2 years
measure: The incidence of subclinical cardiovascular disease in the study population
timeFrame: 2 years
measure: The change in in 10-year cardiovascular disease risk between the control group and intervention group using both prediction models.
timeFrame: 2 years
measure: Change in total cholesterol (mmol/L) including the derivatives (which are combined to give the total cholesterol) high-density lipoprotein (mmol/L), low-density lipoprotein (mmol/L) and non-high-density lipoprotein (mmol/L).
timeFrame: 2 years
measure: Fibroscore (Kilopascals)
timeFrame: 2 years
measure: Change in HBA1C (mmol/mol)
timeFrame: 2 years
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
Study officials:
References: