Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II
Conditions
Brief summary
The purpose of the study is to determine whether ezetimibe plus simvastatin will be more effective than simvastatin alone in preventing progression of atherosclerosis of the inner layer of the carotid artery.
Interventions
DRUGezetimibe (plus simvastatin)
oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
DRUGplacebo (plus simvastatin)
tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
Sponsors
Merck Sharp & Dohme LLC
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Genotype-confirmed heterozygous familial hypercholesterolemia with written documentation of the genetic diagnosis at the time of screening and LDL-C \>=210 mg/dL (5.43 mmol/L), or clinical diagnosis of heterozygous familial hypercholesterolemia, defined as LDL-C \>=210 mg/dL (5.43 mmol/L) and at least one of the following: * tendinous xanthoma * child \<18 years of age with hypercholesterolemia (LDL-C \>159 mg/dL (4.11 mmol/L) * has a sibling with hypercholesterolemia (LDL-C \>190 mg/dL \[4.91 mmol/L\]) and tendinous xanthoma * family history with an LDL-C value distribution pattern compatible with dominant autosomal transmission and at least one relative presenting fasting total cholesterol values \>348 mg/dL (9.0 mmol/L) after exclusion of secondary causes of dyslipidemia * LDL-C \>=210 mg/dL (5.43 mmol/L) 1 week before randomization * plasma triglyceride level \<=400 mg/dL (4.52 mmol/L)
Exclusion criteria
* pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study * presence of an apolipoprotein B gene mutation with confirmed absence of an LDL receptor mutation in either allele * undergoing LDL-apheresis or plasma apheresis * unsuitable plaque or artery morphology * use of certain drugs, foods, or other agents known to alter cholesterol levels or to cause pharmacokinetic interactions with either ezetimibe or simvastatin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint. | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint. | 24 months |
| Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint. | 24 months |
| Proportion of subjects developing new carotid artery plaques between baseline and endpoint. | 24 months |
| Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint. | 24 months |
Outcome results
None listed