Laufzeit: 13.09.2019 - 31.12.2025
Nummer Ethikantrag: 2018-004565-14
Beschreibung der Studie
Doppelblinde, randomisierte, placebo-kontrollierte, multizentrische Studie zur Beurteilung der Auswirkung von Evolocumab auf größere kardiovaskuläre Ereignisse bei Patienten mit hohem kardiovaskulären risiko ohne vorangegangenen Myokardinfarkt oder Schlaganfall
1. Subject has provided informed consent prior to initiation of any study specific activities/procedures
2. Adult subject ≥ 50 years (men) or ≥ 55 years (women) to < 80 years of age (either sex)
3. Subjects must have an LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) or non-HDL-C ≥ 130 mg/dL (≥ 3.4mmol/L) at screening, after ≥ 4 weeks of optimized lipid-lowering therapy (see Section 12.8 of the protocol).
4. Diagnostic evidence of at least 1 of the following (A— D) at screening:
A) Significant coronary artery disease meeting at least 1 of the following criteria:
> History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following:
- multi-vessel percutaneous coronary intervention (PCI)
- PCI or coronary artery bypass grafting (CABG) with residual ≥ 50% stenosis in a separate, unrevascularized segmentor vessel, or
- multi-vessel CABG at least 5 years prior to screening
> Significant coronary disease without prior revascularization as evidenced by either a ≥ 70% stenosis of at least 1 coronary artery, ≥ 50% stenosis of 2 or more coronary arteries, or ≥ 50% stenosis of the left main coronary artery
> known coronary artery calcium score ≥ 100
B) Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria:
- prior transient ischemic attack with ≥ 50% carotid stenosis
- carotid artery stenosis of ≥ 70% or 2 or more ≥ 50% stenosis
- prior carotid artery revascularization
C) Significant peripheral arterial disease meeting at least 1 of the following criteria:
- ≥ 50% stenosis in a limb artery
- history of abdominal aorta treatment (percutaneous and surgical)
- ankle brachial index (ABI) < 0.85
D) Diabetes mellitus with at least 1 of the following:
- known microvascular disease, defined by diabetic nephropathy or treated retinopathy. Diabetic nephropathy defined as microalbuminuria (urinary albumin to creatinine ratio ≥ 30mg/g) and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
- chronic treatment with insulin
- diabetes diagnosis ≥ 10 years ago
5. At least 1 of the following high risk criteria at screening (most recent lab values prior to screening, as applicable):
- polyvascular disease, defined as coronary, carotid, or peripheral artery stenosis ≥ 50% in a second distinct vascular location in a patient with coronary, cerebral or peripheral arterial disease (inclusion criterion 104 A-C)
- diabetes or known evidence of metabolic syndrome (Section 12.9 of the protocol) in a subject with coronary, cerebral, or peripheral artery disease (inclusion criterion 104 A-C)
- at least 1 coronary, carotid, or peripheral artery stenosis of >= 50% in a patient with diabetes meeting inclusion criterion 104 D
- LDL ≥ 130 mg/dL (≥ 3.4 mmol/L) or non-HDL ≥ 160 mg/dL (> 4.2 mmol/L)
- lipoprotein (a) > 125 nmol/L (50 mg/dL)
- known familial hypercholesterolemia
- family history of premature coronary artery disease defined as an MI or CABG in the subject’s father or brother at age < 55 years or an MI or CABG in the subject’s mother or sister at age < 60 years
- high sensitive c-reactive protein ≥ 3.0 mg/L
- current tobacco use
- ≥ 65 years of age
- menopause before 40 years of age
- eGFR 15 to < 45 mL/min/1.73 m2
- MI or stroke prior to randomization .
- CABG < 3 months prior to screening.
- Uncontrolled or recurrent ventricular tachycardia.
- Atrial fibrillation not on anticoagulation therapy.
- Uncontrolled hypertension (sitting systolic blood pressure > 180 mmHg or diastolic blood
- pressure > 110 mmHg) at screening.
- Last measured left-ventricular ejection fraction < 30% or New York Heart Association (NYHA)
- Functional Class III/IV.
- Diagnostic Assessments
- Fasting triglycerides ≥ 500 mg/dL (5.7 mmol/L) at screening.
- End stage renal disease (ESRD), defined as an eGFR < 15 mL/min/1.73 m2 or receiving dialysis at screening.
Other Medical Conditions
- Malignancy, except non-melanoma skin cancers, or in situ cancers of the cervix, prostate, or
- breast duct within 5 years prior to screening.
- History or evidence of clinically significant disease (eg, malignancy, respiratory, gastrointestinal, renal or psychiatric disease) or unstable disorder that, in the opinion of the investigator(s), Amgen physician or designee would pose a risk to the patient’s safety or interfere with the study assessments, procedures, completion, or result in a life expectancy of less than 1 year.
- Previously received or receiving evolocumab or any other therapy to inhibit PCSK9.
- Previously received a cholesterol ester transfer protein (CETP) inhibitor (ie, anacetrapib,
- dalcetrapib, evacetrapib), mipomersen, lomitapide, or has undergone LDL-apheresis in the last 12 months prior to LDL-C screening.
Prior/Concurrent Clinical Study Experience
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies).
- Female subject is pregnant, had a positive pregnancy test at screening, breastfeeding, or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product.
- Female subjects of childbearing potential unwilling to use 1 acceptable method of effective
- contraception during treatment and for an additional 15 weeks after the last dose of investigational product. Refer to Section 12.5 of the protocol for additional contraceptive
- Subject has known sensitivity to any of the products or components to be administered during dosing.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
- Subject is staff personal directly involved with the study or is a family member of the investigational study staff.
- Subject met eligibility criteria but did not enroll .
Ziel der Studie
Ziel unserer Foschung ist es, zu prüfen, ob die Senkung des Cholersterinspiegels in Ihrem Blut durch Evolocumab, das zusätzlich zu Ihrer derzeitigen medizinischen Therapie eingenommen wird, das Risiko für Herz-Kreislauf-Erkrankungen oer Ereignisse (z.B. Herzinfarkt oder Schlaganfall) verringert.
Dr. med. Manuela Licka
Dr. med. Manuela Licka