Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05639218 |
| Other study ID # |
PCSK9I-0621 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 29, 2021 |
| Est. completion date |
December 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Pauls Stradins Clinical University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Lipid accumulation, with mostly emphasized role of low-density lipoprotein cholesterol
(LDL-C), is the pathogenetic cornerstone of atherosclerotic cardiovascular disease. Standard
hypolipidemic therapy, based on statins and ezetimibe, does not always decrease LDL-C levels
enough to achieve therapeutic goals. A novel and promising direction is inhibition of
proprotein convertase subtilisin/kexin type 9 (PCSK9) in hepatocytes, subsequently reducing
LDL-C receptor degradation and increasing intracellular LDL-C uptake.
Aim of this study is to evaluate the effect of optimal hypolipidemic pharmacotherapy,
including PCSK9 inhibitors and inclisiran, on plasma lipid profile and qualitative features
of atherosclerotic plaques in very-high cardiovascular risk patients.
This study enrolls patients with an established atherosclerotic cardiovascular disease,
receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally
tolerated dose and/or ezetimibe.
Effect of hypolipidemic pharmacotherapy is evaluated by analysis of plasma lipid profile
parameter changes and qualitative features of atherosclerotic plaques using Near-Infrared
Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.
Results of the study would be sufficient for complementing evidence regarding therapeutic
strategy in very-high cardiovascular risk patients.
Description:
Background:
Lipid accumulation in artery walls is the pathogenetic cornerstone of atherosclerosis. The
most commonly studied risk factor of atherosclerotic cardiovascular disease is low-density
lipoprotein cholesterol (LDL-C), nevertheless other plasma lipids have an established role as
well. LDL-C is considered the primary target for cardiovascular risk reduction, with
therapeutic goal <1.4 mmol/l in very-high cardiovascular risk patients with established
atherosclerotic cardiovascular disease. Standard hypolipidemic therapy, based on statins and
ezetimibe, is not always effective enough. Novel and promising direction is proprotein
convertase subtilisin/kexin type 9 (PCSK9) - protease that binds LDL receptors in
hepatocytes, subsequently promoting their lysosomal degradation. This process leads to
reduced intracellular LDL-C uptake and increased LDL-C concentration in plasma. PCSK9
inhibitors - monoclonal antibodies evolocumab and alirocumab are successfully used in
clinical practice, with a proven effectiveness in clinical trials ODYSSEY and FOURIER. An
innovative medication is inclisiran - small interfering ribonucleic acid (siRNA) molecule
that interferes with translation of messenger RNA (mRNA) of PCSK9 in hepatocytes as a result
of complementary binding. Subsequently levels of synthesized PCSK9 are reduced, resulting in
positive impact on plasma lipid profile. Inclisiran has demonstrated remarkable efficacy and
safety profile in ORION clinical trials, being registered in European Medicines Agency since
year 2020. Real-world data regarding optimal lipid-lowering pharmacotherapy, including
experience with new medications, is of great clinical interest, studying effect on plasma
lipid profile, as well as qualitative features of atherosclerotic plaques using Near-Infrared
Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.
Aim:
Aim of this study is to evaluate effect of optimal hypolipidemic pharmacotherapy on plasma
lipid profile and and qualitative features of atherosclerotic plaques in very-high
cardiovascular risk patients receiving PCSK9 inhibitors or inclisiran as add-on treatment to
statins in maximally tolerated dose and/or ezetimibe.
Study design:
Prospective observational study.
Study population:
Very-high cardiovascular risk patients with an established atherosclerotic cardiovascular
disease, receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally
tolerated dose and/or ezetimibe in the context of optimal hypolipidemic pharmacotherapy, in
whom NIRS-IVUS investigation has been performed.
Data acquisition:
Patients fulfilling eligibility criteria and agreeing to participate in the study are
included. Baseline demographic and medical data is acquired, with subsequent follow-up
ambulatory visits after 3 and 6 months after PCSK9 inhibitor or inclisiran therapy
initiation. After 15 months since inclusion, follow-up with NIRS-IVUS performed is foreseen.
For analysis of obtained data MS Excel and IBM SPSS Statistics software is used.
Clinical implications:
Results of this study would be of high clinical interest for complementing evidence and
improving outcomes regarding therapeutic strategy in very-high cardiovascular risk patients
with an established atherosclerotic cardiovascular disease.
