Coronary artery disease (CAD) Optimal treatment approach for bystander lesions in non-infarct related arteries (non-IRA’s) has not been well established. Multiple RCT’s favor preventive PCI over medical treatment, however medical treatment wasn’t optimal in these studies. We want to investigate if optimizing LDL-lowering therapy after an ACS has an effect on functional impairment of a non-IRA lesion and could thus prevent mechanical intervention (PCI or CABG).
Conditions
Interventions
Product Name: Evolocumab or placebo
Product Code: AMG145
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: EVOLOCUMAB
Other descriptive name: AMG145
Concentration unit
Sponsors
Radboudumc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - ACS with PCI of Infarct Related Artery (IRA) - Multi Vessel Disease (MVD) - FFR of non-IRA lesion 0.67 - 0.80 Subjects must have an eligible LDL-C level via local lab assessment based on statin use at screening: - No statin use: = 130 mg/dL (3.3 mmol/l) - Non-intensive statin use (see Table): = 80 mg/dL (2.0 mmol/l) - Intensive statin use (see Table): = 60 mg/dL (1.6 mmol/l) - Age = 18 years at screening 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Refusal or inability to provide informed consent - Prior coronary artery bypass graft - Known left ventricular ejection fraction (LVEF) 50% - Contra-indication for dual antiplatelet therapy - Chronic total occlusion of a non-IRA - Non-IRA stenosis not amenable for PCI treatment (operator’s decision) - Complicated IRA treatment, with one or more of the following: - Extravasation - Permanent no re-flow after IRA treatment (TIMI flow 0-1) - Inability to implant a stent - Known severe cardiac valve dysfunction that will require surgery in the follow-up period. - Known severe kidney disease defined as an eGFR < 30 ml/min. - Severe liver disease defined as Child-Pugh score of 10-15. - Female subject is pregnant, breastfeeding or planning to become pregnant or planning to breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test. - 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. - Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of maximal LDL-C reduction by Evolocumab on top of optimal background lipid-lowering therapy (ESC guidelines) on FFR of non-IRA lesions, in patients presenting with MVD-ACS. ;Secondary Objective: Secondly to correlate baseline lipid core burden with changes in FFR and to investigate the relation between LDL reduction and change in pro-inflammatory monocyte phenotypes.;Primary end point(s): The primary study parameter is the change in FFR from baseline to follow-up in non-IRA lesions. ;Timepoint(s) of evaluation of this end point: At 14 weeks (12+2) participants will undergo FFR/NIRS for a second time, which whill produces the values needed for the primary endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoint is the correlation between baseline Near-InfraRed Spectroscopy (NIRS) derived lipid core burden (MaxLCBI4mm) and change in FFR of the non-IRA.;Timepoint(s) of evaluation of this end point: Please see E.5.1.1 | — |
Countries
Netherlands
Contacts
Public ContactResearch Cardiology Department
Radboudumc
Outcome results
None listed