The Effect of Anacetrapib on Vascular Function and Arterial Stiffness

Study Overview
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Brief Summary
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There are currently no studies evaluating the effect of anacetrapib on blood vessel function and stiffness of the arteries. The REVEAL-Vasc trial will assess whether anacetrapib, in addition to atorvastatin (LDL-C lowering drug) treatment, results in greater endothelial-dependent vascular function and aortic stiffness in patients with established cardiovascular disease, compared to adding placebo. Participants will be asked to provide a blood sample and pulse Wave Velocity/Pulse Wave Analysis and Flow Mediated Dilation will be carried out to assess blood vessel function and stiffness of the arteries. REVEAL-Vasc is an investigator led sub-study of HPS3/TIMI 55: REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid modification): A large-scale, randomized placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease (NCT01252953) which is coordinated by OXFORD CTSU. No treatment will be received on this sub-study, therefore only participants who have been enrolled in HPS3/TIMI55 REVEAL in which participants received anacetrapib with atorvastatin or placebo will be considered for this trial.

Detailed Description
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REVEAL-Vasc is an investigator led sub-study of HPS3/TIMI 55: REVEAL. Participants who previously enrolled on HPS3/TIMI 55: REVEAL and received treatment will be invited to participate in this sub-study. Participants will attend a screening and an assessment visit during which Pulse Wave Velocity/ Pulse Wave Analysis and Flow Mediated Dilation will be carried out to assess blood vessel function and stiffness. A blood sample will also be taken from participant to assess CRP and lipid profile. Since participants will have received treatment on the main trial HPS3/TIMI 55: REVEAL, no treatment will be received on this sub-study.

Official Title
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A Cross-sectional REVEAL Sub-study Evaluating the Effect of Anacetrapib on Vascular Function and Arterial Stiffness [An Investigator Led Sub-study of HPS3/TIMI 55: REVEAL]

Conditions
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Atherosclerotic Cardiovascular Disease, Vascular Disease

Intervention / Treatment
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* Drug: Anacetrapib
* Drug: Statin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have been randomised into the HPS3/TIMI 55- REVEAL study (NCT01252953) Exclusion Criteria: Any concomitant condition that, at the discretion of the investigator, may affect the participant's ability to complete the study or study procedures Atrial fibrillation at time of assessment Inability to provide informed consent Inability to refrain from caffeine containing products for 6 hours prior to study visit Inability to refrain from smoking for 2 hours prior to study visit

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anacetrapib<br>Participants who received anacetrapib, in addition to statin on the HPS3/TIMI 55: REVEAL trial. | Drug: Anacetrapib<br>* No drug administration will occur on this sub-study. Participants will receive treatment on the main trial HPS3/TIMI 55: REVEAL (NCT01252953)<br>Drug: Statin<br>* No drug administration will occur on this sub-study. Participants will receive treatment on the main trial HPS3/TIMI 55: REVEAL (NCT01252953)<br>|
| Placebo<br>Participants who received placebo, in addition to statin on the HPS3/TIMI 55: REVEAL trial. | Drug: Statin<br>* No drug administration will occur on this sub-study. Participants will receive treatment on the main trial HPS3/TIMI 55: REVEAL (NCT01252953)<br>Drug: Placebo<br>* No drug administration will occur on this sub-study. Participants will receive treatment on the main trial HPS3/TIMI 55: REVEAL (NCT01252953)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of treatment on flow-mediated dilation (FMD) | Measured by FMD as a surrogate measure of endothelial-dependent vasodilation | Visits 0-1 (day 0 up to approximately day 28 depending on scheduling of visits) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of treatment on aortic (carotid-to-femoral) Pulse Wave Velocity (PWV) | Measured by PWV as a surrogate measure of aortic stiffness | Visits 0-1 (day 0 up to approximately day 28 depending on scheduling of visits) | 
| The effect of treatment on central blood pressure | As a measure of central haemodynamics | Visits 0-1 (day 0 up to approximately day 28 depending on scheduling of visits) | 
| The effect of treatment on sublingual glyceryl trinitrate (GTN) response on artery dilation | Measured by FMD as a surrogate measure of endothelial-independent vasodilation | Visits 0-1 (day 0 up to approximately day 28 depending on scheduling of visits) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular Diseases, Lipids, Cholesteryl Ester Transfer Protein (CETP) Inhibition, Anacetrapib, Cardiovascular Disease, Cholesterol