Patients presenting with acute myocardial infarction (non-ST-elevation myocardial infarction or acute ST-elevation myocardial infarction) and with elevated cholesterol levels. MedDRA version: 20.0 Level: LLT Classification code 10028597 Term: Myocardial infarction acute System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Praluent
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: ALIROCUMAB
Other descriptive name: ALIROCUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Insel Gruppe AG - Inselspital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Acute myocardial infarction: acute ST-segment elevation myocardial infarction (STEMI) with pain onset within =24h, or non-ST segment elevation myocardial infarction (NSTEMI), with at least one coronary segment (culprit lesion) requiring PCI; LDL-C =70 mg/dL (=1.8 mmol/L) assessed prior to, or during PCI in patients who have been receiving any stable statin regimen within = 4 weeks prior to enrollment; OR LDL-C =125 mg/dL (=3.2 mmol/L) in patients who are statin-naïve or have not been on stable statin regimen for = 4 weeks prior to enrollment; At least two major native coronary arteries ("target vessels") each meeting the following criteria for intracoronary imaging immediately following the qualifying PCI procedure; Hemodynamic stability allowing the repetitive administration of nitroglycerine; Ability to understand the requirements of the study and to provide informed consent; Willingness to undergo follow-up intracoronary imaging Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 168 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 126
Exclusion criteria
Exclusion criteria: Left-main disease, defined as =50% reduction in lumen diameter of the left main coronary artery by angiographic visual estimation; Three-vessel disease; History of coronary artery bypass surgery; TIMI flow <2 of the infarct-related artery after PCI; Unstable clinical status (hemodynamic or electrical instability); Significant coronary calcification or tortuosity deemed to preclude IVUS, NIRS and OCT evaluation; Uncontrolled cardiac arrhythmia; Severe renal dysfunction; Active liver disease or hepatic dysfunction; Known intolerance to rosuvastatin OR known statin intolerance ; Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel; Known sensitivity to any substances to be administered, including known statin intolerance Patients who previously received alirocumab or other PCSK9 inhibitor; Patient who received cholesterol ester transfer protein inhibitors in the past 12 months prior to screening; Treatment with systemic steroids or systemic cyclosporine in the past 3 months; Known active infection or major hematologic, metabolic, or endocrine dysfunction; Planned surgery within 12 months; Patients who will not be available for study-required visits; Current enrollment in another investigational device or drug study; History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer; Estimated life expectancy less than 1 year; Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of the PCSK9 inhibitor alirocumab on the change in percent atheroma volume (PAV) at week 52 in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) in the infarct-related artery and receiving uidelinerecommended high-intensity statin therapy.;Secondary Objective: To evaluate the effect of the PCSK9 inhibitor alirocumab on the change in lipid core burden index (defined by NIRS), macrophage accumulation, and fibrous cap thickness of coronary plaques (defined by OCT) as compared with placebo in the non-infarct-related coronary arteries; To assess the effect of alirocumab on change in lipid levels (cholesterol, LDL-C, HDL-C, Lp(a), triglycerides, non-HDL-C, Apo B, Apo A-1, ratio Apo B/Apo A-1, Apo C-III), inflammatory biomarkers (hs-CRP, TNFa, IL-1b, IL-6, MPO, cystatine, SIRT1, SIRT6) and other selected biomarkers (hs-troponin T, NT-pro-BNP) and explore possible associations with changes in coronary plaque characteristics; To evaluate adverse events in patients treated with alirocumab.;Primary end point(s): The primary endpoint is the change in percent atheroma volume (PAV) as determined by IVUS, between baseline and 52-week follow-up from matched regions of interest. This endpoint is used for the pre-specified sample size calculation;Timepoint(s) of evaluation of this end point: Follow up at week 52 (or as soon as possible, when the COVID-19 restrictions allow study visits). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in lipid-core burden index (LCBItotal) as determined by NIRS, between baseline and 12-month follow-up from matched ROI; Change in maximum LCBI in any 4-mm segment (maxLCBI4mm) as determined by NIRS; Change in minimal and fibrous mean cap thickness as determined by OCT; Change in Average Angular Extension (AAE) of macrophages as determined by OCT, between baseline and 12-month follow-up from matched ROI; Change in normalized total atheroma volume (NTAV); Change in LDL-cholesterol, hs-CRP, hs-TnT and NT-pro-BNP as well as lipid and inflammatory markers between baseline (Week 0), Week 4, and Week 52; Association between levels of biomarkers and changes in plaque characteristics as described in the primary and secondary imaging endpoints; Death, cardiac death, myocardial infarction, any coronary revascularization, stroke, transient ischemic attack; Adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), product complaints, laboratory data.;Timepoint(s) of evaluation of this end point: Followup at week 52 and week 4 (biomarkers) | — |
Countries
Austria, Denmark, Netherlands, Switzerland
Contacts
Public ContactProf. Dr. Irene Lang
AKH Vienna, Medical University of Vienna
Outcome results
None listed