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
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- 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).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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.
研究组 & 干预措施
Bictarvy
Intervention group: those randomised to switch antiretroviral therapy to Bictegravir, Emtricitabine and Tenofovir Alafenamide fixed dose combination.
干预措施: Biktarvy (Drug)
结局指标
主要结局
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).
时间窗: 2 years
CT based quantification of coronary artery disease burden. Assessed using summary statistics and parametric or non-parametric measures of significance.
Drop out rate
时间窗: 2 years
Drop out rate of the main study. The number of participants not completing the study expressed as a percentage of those recruited.
Number of adverse plaque features
时间窗: 2 years
The change in the number of coronary segments displaying an adverse plaque characterisitc. This is defined as any one of the following (low attenuation plaque (\<30 hounsfield units), positive remodelling (remodelling index \>1.1), spotty calcification or napkin ring sign). Change in number of adverse plaque features will be assessed using summary statistics and parametric or non-parametric measures of significance.
Change in segmental stenosis score
时间窗: 2 years
Coronary segments are graded as normal (no stenosis), stenosis 1%-29%, 30%-49%, 50%-69%, ≥70% by visual semiquantification method, with assignment of scores of 0, 1, 2, 3, or 4, respectively. Stenosis is not measured when the vessel diameter was \<2 mm. Total segment stenosis score (TSS) per person is calculated by summing all the 15 individual SSSs with a possible score ranging from 0 to 60. Change in segmental stenosis scores will be assessed using summary statistics and parametric or non-parametric measures of significance.
The rate of recruitment to the HART CT study
时间窗: 2 years
Rate of recruitment to the main study expressed as a rate of eligible patients screened to those who undergo randomisation.
Change in Agatston Score (Agatston units).
时间窗: 2 years
Agatston calcium scoring is a highly reproducible well validated scale outlining the burden of calcific coronary artery disease. Agatston score is a function of calcium volume and density. The volume is calculated in mm3 and multiplied by a density weighting factor depending on the haunsfied units. Change in Agatston scores will be assessed using summary statistics and parametric or non-parametric measures of significance.
次要结局
- The incidence of subclinical cardiovascular disease in the study population(2 years)
- 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).(2 years)
- Fibroscore (Kilopascals)(2 years)
- Change in HBA1C (mmol/mol)(2 years)
- Inter and intraobserver variability of CT based outcome measures(2 years)
- The change in in 10-year cardiovascular disease risk between the control group and intervention group using both prediction models.(2 years)