Primary objective- To evaluate the effect of LDL-C lowering by means of the PCSK9 inhibitor alirocumab as compared with placebo on the change in percent atheroma volume (PAV) in non-infarct-related coronary arteries of patients who present with…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Change in percent atheroma volume (PAV)
Secondary outcome
- Change in lipid core burden index (defined by NIRS), macrophage accumulation,
and fibrous cap thickness of coronary plaques (defined by OCT)
- 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)
Safety objective
- Amount of adverse events
Background summary
Coronary artery disease (CAD) is the most frequent cause of mortality in the
industrialized world. Hypercholesterolemia is a major risk factor for the
development and progression of CAD. HMG-CoA reductase inhibitors (statins)
lower plasma levels of low-density lipoprotein cholesterol (LDL-C), and they
reduce cardiovascular mortality in proportion to the magnitude of LDL-C
lowering. While statins currently represent the first-line, gold-standard
therapy for primary and secondary prevention of cardiovascular morbidity and
mortality, nearly 50% of patients in Europe and Canada treated with statins do
not achieve their target levels of LDL-C or cannot tolerate effective statin
doses; subsequently, substantial LDL-associated residual risk remains.
Therefore, there has been increasing interest for additional pharmacologic
strategies to effectively lower cholesterol and to further reduce
cardiovascular events.
Study objective
Primary objective
- To evaluate the effect of LDL-C lowering by means of the PCSK9 inhibitor
alirocumab as compared with placebo on the change in percent atheroma volume
(PAV) in non-infarct-related coronary arteries of patients who present with
acute myocardial infarction, undergo percutaneous coronary intervention (PCI)
in the infarct-related artery, and receive guideline-recommended high-intensity
statin therapy.
Secondary objectives
- 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.
Safety objective
To evaluate adverse events in patients treated with alirocumab.
Study design
This is a prospective, randomized, superiority, double-blind (assessor and
patients blinded to treatment), placebo-controlled, parallel-group,
multi-center study to evaluate the effect of alirocumab on coronary
atherosclerotic plaque burden and composition as assessed by multi-modality
intracoronary imaging at baseline and following 52 weeks of treatment in
patients presenting with acute myocardial infarction undergoing PCI. The
primary endpoint will be assessed at 52 weeks post randomization (or as soon as
possible, when the COVID-19 restrictions allow study visits).
Intervention
At the start of the study and after 1 year IVUS, NIRS and OCT imaging will be
performed in 2 non-infarct related coronary arteries. At 2, 4 and 24 weeks, a
visit to the Erasmus MC will be performed, and at 8, 12, 36, and 48 weeks
telephone calls will be performed. During the visits, the patient will be
trained for self-administration of the medication. By telephone calls
performing by the investigational team, potential adverse events will be
registered and regularly administration of the medication will be ensured. At
52 weeks (or as soon as possible, when the COVID-19 restrictions allow study
visits), a final visit will be performed during which i.e. intracoronary
imaging will be performed.
Study burden and risks
The investigational product is generally well-tolerated by healthy study
subjects and patients with increased cholesterol levels in the blood. In 1% to
10% of the subjects, the following adverse events took place:
* injection site reaction (redness, itch, swelling/sensitivity)
* cough, cavity inflammation, bronchial inflammations
* myalgia
* itch
* diarrhea
In rare cases (<0.5%) the imaging techniques can damage the coronary arteries
(rift, blood clot formation) that may needs to be treated with an additional
stent.
Freiburgstrasse 8
Bern 3010
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Freiburgstrasse 8
Bern 3010
CH
Listed location countries
Age
Inclusion criteria
- Male or female, age *18 years at screening
- 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:
- Angiographic evidence of <50% reduction in lumen diameter by angiographic
visual estimation
- Target vessel deemed to be accessible to imaging catheters and suitable for
intracoronary imaging in the proximal (50mm) segment (*target segment*)
- Target vessel may not be a bypass (saphenous vein or arterial) graft or a
bypassed native vessel
- Target vessel must not have undergone previous PCI within the target segment
- Target vessel is not candidate for intervention at the time of qualifying PCI
or over the following 6 months in the judgment of the Investigator
- 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
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, defined as *70% reduction in lumen diameter of three
major epicardial coronary arteries by angiographic visual estimation or in
major branches of one or more of these arteries, irrespective of the
localization (proximal 50mm or more distal localization) of the obstructive
lesions
- 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, defined as recurrent and symptomatic
ventricular tachycardia or atrial fibrillation with rapid ventricular response
not controlled by medications in the past 3 months prior to screening
- Severe renal dysfunction, defined by estimated glomerular filtration rate <30
ml/min/1.73m2
- Active liver disease or hepatic dysfunction;
- Known intolerance to rosuvastatin OR
Known statin intolerance defined by the following criteria: inability to
tolerate at least 2 different statins (one statin at the lowest starting
average daily dose and the other statin at any dose); intolerance associated
with confirmed, intolerable statin-related adverse effect(s) or significant
biomarker abnormalities; symptom or biomarker changes resolution or significant
improvement upon dose decrease or discontinuation; and symptoms or biomarker
changes not attributable to established predispositions such as drug-drug
interactions and recognized conditions increasing the risk of 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 in the judgment of the Investigator
- Planned surgery within 12 months
- Patients who will not be available for study-required visits in the judgment
of the Investigator
- 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001502-15-NL |
| ClinicalTrials.gov | NCT03067844 |
| CCMO | NL61713.078.17 |