Investigating the Lowest Threshold of Vascular Benefits From LDL Cholesterol Lowering in Patients With Stable CV Disease

Sponsor
Cambridge University Hospitals NHS Foundation Trust
Study ID
NCT03355027
Status
Unknown

Conditions

  • Atherosclerosis
  • Cardiovascular Diseases

Eligibility Criteria

Sex
ALL
Age
40 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Alirocumab 150 MG/ML — DRUG
    Dosing to be performed by subcutaneous injection in clinic
  • Ezetimibe 10Mg Tablet — DRUG
    Patients will be instructed to take once daily at night.
  • Atorvastatin 40Mg Tablet — DRUG
    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)
  • Atorvastatin 80Mg Tablet — DRUG
    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)
  • Rosuvastatin 20Mg Tablet — DRUG
    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)
  • Rosuvastatin 40Mg Tablet — DRUG
    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)
  • Simvastatin 80mg — DRUG
    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)

Study Details

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.

Key Dates

Start date
Nov 30, 2017
Status verified
Jul 2021
Primary completion
Sep 30, 2019
Completion
Nov 30, 2023

Study Design

Enrollment
60 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Alirocumab Treatment Arm
    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.
  • Active Comparator: Comparator Treatment Arm
    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.

Primary Outcome Measure

Vascular inflammation (Standard Uptake Value) - Carotid artery [ Time Frame: 8 weeks ]

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