An interventional study of Alirocumab 150 MG/ML and Ezetimibe 10Mg Tablet in Atherosclerosis and Cardiovascular Diseases, sponsored by Cambridge University Hospitals NHS Foundation Trust. Status unknown at 1 site in United Kingdom. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2021-07-23.
Sponsored by Cambridge University Hospitals NHS Foundation Trust · Not applicable, Interventional, and Basic science
The INTENSITY-HIGH study aims to answer if there are any limits to LDL reduction in relation to benefiting vascular health, exploring the mechanisms by which secondary prevention in patients with established heart disease may benefit from even lower LDL levels. By using PCSK9 inhibitors such as Alirocumab, very low LDL cholesterol levels not previously encountered in statin trials, can be achieved in patients with established heart disease on top of intensive statin treatment.
This research is being carried out because it is unclear what the lowest threshold of LDL cholesterol should be to attain significant reductions in CV risk in stable cardiovascular patients. It is unknown whether there is a true limit of LDL cholesterol below which there is no further improvement in endothelial function in stable cardiovascular patients, and, whether this is associated with a reduction in markers of both systemic and vascular inflammation.
Defining this may help identify individuals from the general population who may benefit from more aggressive lipid lowering treatment than standard statin treatment in terms of CV morbidity and mortality.
This study will be conducted in patients with stable cardiovascular disease, where they will be randomized to receive either a combination of Alirocumab and statin, or Ezetimibe plus statin. 60 patients will be recruited to this single center, randomized, open label, parallel group, mechanistic physiological study which will be conducted at Cambridge University Hospitals NHS Foundation Trust. In order to be eligible for enrollment to the study, some patients may have to complete a 4 week washout period on a suitable statin therapy. The total study duration for each participant will be approximately 14 weeks, where a series of non-invasive vascular studies and medical imaging assessments which will be conducted to observe vascular/systemic inflammation and to assess endothelial vascular function.This study is funded by JP Moulton Charitable Foundation.
The INTENSITY-HIGH study primarily seeks to explore the physiological mechanisms (mainly using endothelial function and vascular imaging of inflammation) by which secondary prevention in patients with established cardiovascular disease may benefit from even lower LDL levels using PCSK9 therapies. This will then set the basis for potential changes to guidelines about what a "healthy cholesterol" level should be and the targets these should be achieving, or indeed if there is a plateau beyond which there is no further benefit on surrogates of CV disease.
Endothelial function can be measured in the peripheral vasculature in a number of different ways, which include venous occlusion plethysmography with intra-arterial infusions of acetylcholine, ischemia flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery, reactive hyperemia peripheral arterial tonometry (RH-PAT) and others. A venous plethysmography measure of forearm blood flow to intra-arterial acetylcholine infusion is the most sensitive and direct measurement of endothelium release of nitric oxides, but is more invasive than other techniques. FMD is non-invasive and measures changes in the brachial artery to ischemia. It is acknowledged that whilst FMD has a larger coefficient variation and is more technician dependent, it is more patient-friendly in that it is of shorter duration procedure wise, is non-invasive and is repeatable over a short period; therefore we have employed this technique in this study to improve chances of patient acceptability. RH-PAT is an alternative non-invasive assessment which measures volume changes at the fingertip (a surrogate of reactive hyperemia), is easy to implement and is not operator dependent. However, as yet it remains not well validated. Therefore, flow mediated dilatation has been selected for this study.
Metabolically active inflammatory cells utilize more glucose than non-activated cells, and the degree of metabolic activity can be measured using 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Cellular FDG uptake is largely irreversible and correlates with glucose usage and macrophage numbers in both tumor cells and atherosclerotic plaques [38, 39]. FDG PET imaging has been successfully used to determine culprit plaques responsible for TIA and stroke [4042]. The signal has also been shown to be responsive to therapy, with clear reductions in FDG uptake noted in both humans and animal models of atherosclerosis [43, 44]. In addition, very recently, it has been shown that FDG-PET/CT is a reliable technique to assess changes in plaque structure with good reproducibility [40]. Taken together, these findings suggest a role for FDG PET/CT imaging in the assessment of the antiinflammatory potential of novel compounds such as PCSK9 therapies.
1,517 studies on the registry are indexed under Atherosclerosis; 224 are open to participants now.
This study's enrollment of 60 is below the median of 100 across 879 interventional studies indexed under Atherosclerosis.
Browse Atherosclerosis studies →Cambridge University Hospitals NHS Foundation Trust is the lead sponsor of 171 studies on the registry; 37 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
High risk is defined as a history of any of the following: acute coronary syndrome (such as myocardial infarction or unstable angina requiring hospitalisation), coronary or other arterial revascularisation procedures, chronic heart disease, ischaemic stroke, peripheral arterial disease.
Very high risk is defined as recurrent cardiovascular events or cardiovascular events in more than 1 vascular bed (that is, polyvascular disease).
Exclusion Criteria:
Inclusion/Exclusion Criteria for INTENSITY-HIGH PET/MR sub-study (optional)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
30 patients with stable cardiovascular disease to receive Alirocumab 150mg \& prescribed one of the following: Atorvastatin 40mg/80mg or Simvastatin 80mg or Rosuvastatin 20mg/40mg. Dosing and dispensing to be performed at V3, V4, V5 and V6.
Drug: Alirocumab 150 MG/ML · Drug: Atorvastatin 40Mg Tablet · Drug: Atorvastatin 80Mg Tablet · Drug: Rosuvastatin 20Mg Tablet · Drug: Rosuvastatin 40Mg Tablet · Drug: Simvastatin 80mg
30 patients with stable cardiovascular disease to receive Ezetimibe 10mg \& prescribed one of the following: Atorvastatin 40mg/80mg or Simvastatin 80mg or Rosuvastatin 20mg/40mg. Dosing and dispensing to be performed at V3, V4, V5 and V6.
Drug: Ezetimibe 10Mg Tablet · Drug: Atorvastatin 40Mg Tablet · Drug: Atorvastatin 80Mg Tablet · Drug: Rosuvastatin 20Mg Tablet · Drug: Rosuvastatin 40Mg Tablet · Drug: Simvastatin 80mg
Drug page: Alirocumab
Dosing to be performed by subcutaneous injection in clinic
Also known as: Praluent
Patients will be instructed to take once daily at night.
Also known as: Ezetrol
Patients will be instructed to take once daily at night. Atorvastatin will be the preferred statin option for those with eGFR \< 60 ml/min/1.73m2. Patient may be required to complete a 4 week run-in period on a statin prior to entering the study (dependent on eligibility)
Patients will be instructed to take once daily at night. Atorvastatin will be the preferred statin option for those with eGFR \< 60 ml/min/1.73m2. Patient may be required to complete a 4 week run-in period on a statin prior to entering the study (dependent on eligibility)
Patients will be instructed to take once daily at night. Rosuvastatin only to be prescribed if atorvastatin and simvastatin are not previously tolerated. Patient may be required to complete a 4 week run-in period on a statin prior to entering the study (dependent on eligibility)
Also known as: Crestor
Patients will be instructed to take once daily at night. Rosuvastatin only to be prescribed if atorvastatin and simvastatin are not previously tolerated. Patient may be required to complete a 4 week run-in period on a statin prior to entering the study (dependent on eligibility)
Also known as: Crestor
Patients will be instructed to take once daily at night. Patient may be required to complete a 4 week run-in period on a statin prior to entering the study (dependent on eligibility)
Vascular inflammation (Standard Uptake Value) - Carotid artery
Change in vascular inflammation in the carotid artery between Alirocumab and Ezetimibe treatment regimes (Vascular inflammation will be quantified by calculating the Standard Uptake Value \[SUV\])
Time frame: 8 weeks
Vascular inflammation (Tissue to Background Ratio TBR) - Carotid artery
Change in vascular inflammation in the carotid artery between Alirocumab and Ezetimibe treatment regimes (Vascular inflammation will be quantified by calculating the Tissue to Background Ratio \[TBR\])
Time frame: 8 weeks
Vascular inflammation (Standard Uptake Value) - Aortic artery
Change in vascular inflammation in the aortic artery between Alirocumab and Ezetimibe treatment regimes (Vascular inflammation will be quantified by calculating the Standard Uptake Value \[SUV\])
Time frame: 8 weeks
Vascular inflammation (Tissue to Background Ratio TBR) - Aortic artery
Change in vascular inflammation in the aortic artery between Alirocumab and Ezetimibe treatment regimes (Vascular inflammation will be quantified by calculating the Tissue to Background Ratio \[TBR\])
Time frame: 8 weeks
Endothelial-dependent vasodilatation (as measured by Flow Mediated Dilatation using high-resolution vascular ultrasound)
Comparing the effects of Alirocumab or Ezetimibe treatment regimes on Flow Mediated Dilatation (a surrogate of endothelial-dependent vasodilatation)
Time frame: 8 weeks
Endothelial-independent vasodilatation (as measured by Flow Mediated Dilatation using high-resolution vascular ultrasound)
Comparing the effects of Alirocumab or Ezetimibe treatment regimes on sublingual glyceryl trinitrate (GTN) response to Flow Mediated Dilatation (a surrogate of endothelial-independent vasodilatation)
Time frame: 8 weeks
Augmentation index (an indicator of arterial stiffness)
Change in Augmentation Index between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Pulse wave velocity
Change in aortic Pulse Wave Velocity between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Carotid IMT
Change in Carotid IMT between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by lipid profile)
Change in systemic inflammation (as measured by lipid profile) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by hsCRP)
Change in systemic inflammation (as measured by hsCRP) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by MMP9)
Change in systemic inflammation (as measured by MMP9) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by IL2)
Change in systemic inflammation (as measured by IL2) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by IL6)
Change in systemic inflammation (as measured by IL6) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Systemic inflammation (as measured by oxLDL lipid subfractions)
Change in systemic inflammation (as measured by oxLDL lipid subfractions) between visits and between Alirocumab or Ezetimibe treatment regimes
Time frame: 8 weeks
Plan to share: No — Only the minimum required participant identifiable information (name and contact details) will be provided to the research team for the purpose of arranging study visits and completing the informed consent process. All delegated research personnel that is responsible to conduct the data/statistical analysis will only analyse data that is anonymised of any patient identifiable data.
This study is status unknown, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Alirocumab
Cambridge University Hospitals NHS Foundation Trust →