E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human immunodeficiency virus (HIV) and cardiovascular disease (CVD) |
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E.1.1.1 | Medical condition in easily understood language |
Human immunodeficiency virus (HIV) and cardiovascular disease (CVD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003581 |
E.1.2 | Term | Asymptomatic HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We will assess the acceptability and suitability of the trial design (including CRF and PIS). This will be assessed by rate of drop out and overall rate of recruitment. The rate of recruitment will also be a determinate factor of the feasibility of any future fully powered study.
To investigate that switching from PI based cART to Biktarvy will result in detectable levels of plaque change on serial CTCA though 48 weeks. This will be assessed by change in TPV, TNCPV, TCPV, SIS, SSS, Agatston score, diameter stenosis and adverse plaque characteristics. We will calculate the standard deviation of these changes to obtain the required sample size for a future appropriately powered randomised control trial. Patients will be recruited from the Royal Liverpool Regional HIV cohort
Patients in both arms of the study will receive routine cardiology care. This may include secondary disease prevention, functional imaging or invasive coronary angiography. Patients in this higher risk category woul |
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E.2.2 | Secondary objectives of the trial |
The CT based scoring tools (MESA and ASTROCHARM calculators) will also be compared to the change in cardiovascular risk derived from traditional scoring systems including QRISK2.
We will assess the prevalence of subclinical cardiovascular disease in our UK HIV cohort.
We will calculate the precision of these CT based measures by assessing the interobserver and intraobserver variability.
We will assess the change in lipid profile and HBA1C. This may give insight on how changes in metabolic profiles (insulin resistance, lipid profile and levels of inflammation) impact on plaque progression / regression and plaque morphology on serial CTCA.
We will measure the change in Fibroscan score (KPa).
Exploratory objectives include to assess how changing ART influences insulin resistance as measured by Kraft testing. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• HIV positive • Undetectable viral load on cART which contain protease inhibitors (duration >6 months at eligibility visit) • Age>40 years at recruitment visit • Stable cART* • No previous documented cardiovascular disease • 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.
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E.4 | Principal exclusion criteria |
• Active liver disease (previously diagnosed) • Renal disease (eGFR <30) • Any ongoing infection • Signficant 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
*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.
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E.5 End points |
E.5.1 | Primary end point(s) |
A quantitative assessment on the change in plaque on serial CTCA to include total plaque volume, calcified plaque volume, non-calcified plaque volume, calcium score (Agatston score), segmental stenosis score, segmental involvement score, diameter stenosis and number of adverse plaque characteristics.
A power calculation will be performed from the standard deviation of outcome measures to allow sample size estimation for a future randomised control trial.
The rate of recruitment and trial dropout rate will be analysed to assess the acceptability of the consent procedure to patients and recruiting clinicians. This will allow a feasibility assessment for a future trial.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Inter and intraobserver variability of measures of plaque on CTCA
The incidence of subclinical cardiovascular disease in the study population The change in in 10-year cardiovascular disease risk between the control group and intervention group using both prediction models.
Change in total cholesterol, High-density lipoprotein, low-density lipoprotein, non-high-density lipoprotein and HBA1C.
Baseline prevalence of fatty liver based on Fibroscore.
Change in the fibroscore between the control group and intervention group
Exploratory Outcomes
Baseline measurement and subsequent change in the following markers of insulin sensitivity: C-peptide, Kraft testing, HOMA-IR
Safety endpoints Any major infection, major adverse cardiac event. HIV safety endpoints – HIV viral load, CD4 count and CD4/CD8 ratio.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Usual antiretroviral regime |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 5 |