AzTrials
AzTrials

Acute Coronary SyndromeGEBINCT04613167

Markers of Cardiovascular Risk in Patients With Premature Coronary Artery Disease and Treatment

A study testing Alirocumab and Evolocumab in people with Acute Coronary Syndrome and Premature Coronary Heart Disease, run by University Medical Centre Ljubljana at 1 site in Slovenia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients with premature coronary heart disease, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Alirocumab and Evolocumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteSlovenia
Study dates
10 Nov 2020to 1 Oct 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • at least 6 months after acute coronary syndrome,
  • up to 55 years at the time of first acute coronary syndrome
  • concentration Lp (a) above 1000 mg / L or Lp (a) above 600 mg / L and LDL above 2.6 mmol / L
  • optimally treated risk factors for cardiovascular events according to currently valid guidelines.

Who cannot join

  • Age <18 years or > 65 years,
  • documented history of myocardial infarction less than 6 months before enrollment
  • secondary dyslipidemia,
  • severe renal disease (oGFR <30 ml / min),
  • moderate to severe liver disease (elevated transaminases above 3 times the norm, elevated bilirubin above 2 times the norm, elevated creatinine kinase above 3 times the norm),
  • acute illness 6 weeks before inclusion in the study,
Show all 10Show fewer
  • history of allergic reaction to any ingredient in the drug,
  • pregnancy and lactation,
  • life expectancy less than 12 months,
  • unwillingness to participate or lack of availability for follow-up

Trial locations and contacts

1 site in 1 country.

Miran Šebeštjen, prof. contact

+38615228541

miran.sebestjen@guest.arnes.si, miran.sebestjen@kclj.si

Andreja Rehberger Likozar, MD contact

+38615228012

rehbergerandreja@gmail.com, andreja.rehbergerlikozar@kclj.si

Slovenia1 site, 1 recruiting

  • University Medical Centre Ljubljana-Department of Vascular diseases and dept. of Cardiology

    Ljubljana, 1000

    Miran Šebeštjen, prof, PhD, +38615224811, miran.sebestjen@kclj.si

    Andreja Rehberger Likozar, MD, +38615228012, andreja.rehbergerlikozar@kclj.si

    Recruiting

Other trials in Slovenia

About this study

Official title: Genetic, Biochemical and Functional Markers of Cardiovascular Risk in Patients With Premature Coronary Artery Disease and Treatment Options

The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients with premature coronary heart disease, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients with early coronary heart disease, to study the effect of alirocumab and evolocumab on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients with early coronary atherosclerosis and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients. Impaired blood fat metabolism and chronic inflammation are intertwined as possible causes of atherosclerosis. Lipoprotein (a) (Lp (a)) is an important risk factor for coronary heart disease and a prognostic predictor in patients after myocardial infarction, but recent research suggests that subtilisin-kexin convertase type 9 (PCSK9) inhibitors are the only drugs that significantly reduce serum Lp (a) concentration. However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with various PCSK9 inhibitors in patients with early coronary heart disease.

Read the detailed description

Impaired blood fat metabolism and chronic inflammation are intertwined as possible causes of atherosclerosis. Lipoprotein (a) (Lp (a)) is a specific subfraction of lipoprotein that is an independent risk factor for coronary heart disease and at the same time predicted residual risk in patients with pre-existing atherosclerosis, regardless of serum LDL-cholesterol concentration. Circulating levels of Lp(a) are mainly genetically determined and varies according to ethnic group. Lp(a) has many functions, which include atherosclerotic, prothrombotic and pro-inflammatory roles. The gene encoding apo (a); LPA, is located on the long arm of chromosome 6 (6q2,6-2,7) and most variants in Lp (a) can be explained by genetic diversity in LPA. To date, the most studied genetic variant is the Kringle-IV type-2 (KIV2) polymorphism, which explains 30-70% of the diversity in Lp (a) in the population. Some KIV2 replicates are associated with smaller isoforms and higher plasma concentrations of Lp (a) which are causally and independently associated with coronary heart disease. Within LPA, the number of KIV2 copies, as well as one nucleotide polymorphism (SNP), rs3798220 and rs10455872, is associated with Lp (a) concentration and coronary heart disease. Recently 'Proprotein convertase subtilisin/kexin type 9' (PCSK9) inhibitors that act through non-specific reduction of Lp(a) are the only drugs that have shown effectiveness in clinical trials, to provide reductions in cardiovascular morbidity and mortality. The effects of PCSK9 inhibitors are not purely through Lp(a) reduction, but also through LDL cholesterol reduction.

The early stage of the atherosclerosis process is characterized by endothelial cell damage, which results in impaired release and function of nitric oxide (NO) from the endothelium. NO is formed by endothelial NO synthetase (NOS-3) from the amino acid L-arginine, which is most pronounced in the vascular wall and is also most important in the process of atherosclerosis. The NOS-3 gene is located on chromosome 7; in the region 7q35-7q36. Functional polymorphisms are those that alter the expression or activity of NOS-3. Among them, rs2070744, rs3918226 and rs1799983 single nucleotide polymorphisms (SNP) are important. Variations in the expression and activity of NOS-3 genetic polymorphisms at exon 7 of the NOS-3 gene are associated with the incidence of myocardial infarction in very young patients who otherwise have a low atheromatous coronary artery load. Variations in the NOS-3 genes cause diversity in NO bioavailability and are responsible for endothelial dysfunction.

A 6-month observational, prospective, and randomized study will include 70 patients with a first acute coronary syndrome (ACS) (including acute transmural myocardial infarction, nontransmural myocardial infarction or unstable angina pectoris) event before age 55 and Lp (a) levels above 1000 mg / L or Lp (a) above 600 mg / L and LDL above 2.6 mmol / L. With the gradual inclusion ("step-wedge") and randomization of patients, the investigators will also provide a control group that will include 30 patients. The investigators will do anamnesis, targeted clinical examination, take blood samples for laboratory measurements, ultrasound measure endothelium-dependent dilatation of the brachial artery and intima media thickness of carotid arteries, measure pulse wave and calculate carotid artery wall stiffness. Patients will be divided into three groups according to a randomization list. The first group will receive alirocumab, the second group evolocumab, and the third group will be the control group and will be included in the treatment after 6 months. During this time, the control group will not receive treatment with alirocumab or evolocumab, only standard treatment. After 6 months, the investigators will repeat all the mentioned investigations. Patients will be informed about the purpose and course of the study before starting it. All will participate voluntarily, without pressure or inappropriate instigation, which they will confirm by signing.

The investigators hypotheses that in patients with early coronary artery disease Lp (a) and Lp (a) polymorphisms are associated with indicators of inflammation and structural-functional properties of the arterial wall; in patients with early coronary artery disease, PCSK9 inhibitors reduce the value of Lp (a), indicators of inflammation and structural and functional involvement of the arterial wall; in patients with early coronary artery disease, the influence of PCSK9 inhibitors on Lp (a), indicators of inflammation and structural-functional properties of the arterial wall depends on the presence of specific polymorphisms for Lp (a).

Being tested
Alirocumab, Evolocumab, Control group
Keywords
Coronary heart disease, Acute coronary syndrome, Lipoprotein (a), Genetics, Secondary prevention, Endothelium, Inflammation, Genetic polymorphisms, NO synthetase, Dyslipidemia
Medical subject headings
Acute Coronary Syndrome, Inflammation, Coronary Disease, Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlirocumabDrug

    The first group will receive alirocumab. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery, intima media thickness of carotid arteries and pulse wave will be measured.

  • EvolocumabDrug

    The second group will receive evolocumab. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery, intima media thickness of carotid arteries and pulse wave will be measured.

  • Control groupDrug

    The third group will receive only optimal guidelines-based secondary preventive treatment. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery, intima media thickness of carotid arteries and pulse wave will be measured.

Study groups in NCT04613167
Study groupRoleWhat they receive
AlirocumabExperimentalThe first group of patients will receive 150 mg of alirocumab every two weeks subcutaneously for 6 months
Receives: Drug: Alirocumab
EvolocumabExperimentalthe second group of patients will receive evolocumab 140 mg every two weeks subcutaneously for 6 months
Receives: Drug: Evolocumab
Control groupExperimentalControl group will be included in the treatment after 6 months. During this time, the control group will not receive treatment with alirocumab or evolocumab, only standard guidelines-based treatment
Receives: Drug: Control group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration

    Functional and morphological characteristics of arterial wall will correlate to Lp (a) concentrations.

    Measured: Baseline

  2. Concentration of Lp (a) and SNP in the LPA gene

    The serum concentration of Lp (a) will correlate with single nucleotide polymorphisms (SNP) in the LPA gene

    Measured: Baseline

  3. The effect of alirocumab or evolocumab on functional and morphological properties of arterial wall after 6 months

    Both drugs will improve functional and morphological properties of arterial wall in with no difference between the drugs. We expect the improvements in each drug group will be in correlation with the decrease of Lp (a) concentration.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2020
  2. Study start10 Nov 2020 (estimated)
  3. Primary completion30 Jun 2021 (estimated)
  4. Study completion1 Oct 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04613167
Sponsor's protocol ID
GEBI
Acronym
GEBI
Status last verified
Oct 2020
First submitted
6 Oct 2020
Last updated
3 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rawther T, Tabet F. Biology, pathophysiology and current therapies that affect lipoprotein (a) levels. J Mol Cell Cardiol. 2019 Jun;131:1-11. doi: 10.1016/j.yjmcc.2019.04.005. Epub 2019 Apr 12.

    PubMed 30986377

  • BERG K. A NEW SERUM TYPE SYSTEM IN MAN--THE LP SYSTEM. Acta Pathol Microbiol Scand. 1963;59:369-82. doi: 10.1111/j.1699-0463.1963.tb01808.x. No abstract available.

    PubMed 14064818

  • Emerging Risk Factors Collaboration; Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009 Jul 22;302(4):412-23. doi: 10.1001/jama.2009.1063.

    PubMed 19622820

  • Julius U, Tselmin S, Schatz U, Fischer S, Bornstein SR. Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors. Clin Res Cardiol Suppl. 2019 Apr;14(Suppl 1):45-50. doi: 10.1007/s11789-019-00099-z.

    PubMed 30838555

  • Maranhao RC, Carvalho PO, Strunz CC, Pileggi F. Lipoprotein (a): structure, pathophysiology and clinical implications. Arq Bras Cardiol. 2014 Jul;103(1):76-84. doi: 10.5935/abc.20140101.

    PubMed 25120086

  • Ma L, Chan DC, Ooi EMM, Barrett PHR, Watts GF. Fractional turnover of apolipoprotein(a) and apolipoprotein B-100 within plasma lipoprotein(a) particles in statin-treated patients with elevated and normal Lp(a) concentration. Metabolism. 2019 Jul;96:8-11. doi: 10.1016/j.metabol.2019.04.010. Epub 2019 Apr 14.

    PubMed 30995439

  • Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res. 2016 Apr;57(4):526-37. doi: 10.1194/jlr.R061648. Epub 2015 Dec 4.

    PubMed 26637278

  • Tsimikas S. A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. J Am Coll Cardiol. 2017 Feb 14;69(6):692-711. doi: 10.1016/j.jacc.2016.11.042.

    PubMed 28183512

  • Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, Bennett D, Silveira A, Malarstig A, Green FR, Lathrop M, Gigante B, Leander K, de Faire U, Seedorf U, Hamsten A, Collins R, Watkins H, Farrall M; PROCARDIS Consortium. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009 Dec 24;361(26):2518-28. doi: 10.1056/NEJMoa0902604.

    PubMed 20032323

  • Chasman DI, Shiffman D, Zee RY, Louie JZ, Luke MM, Rowland CM, Catanese JJ, Buring JE, Devlin JJ, Ridker PM. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis. 2009 Apr;203(2):371-6. doi: 10.1016/j.atherosclerosis.2008.07.019. Epub 2008 Jul 26.

    PubMed 18775538

  • Ober C, Nord AS, Thompson EE, Pan L, Tan Z, Cusanovich D, Sun Y, Nicolae R, Edelstein C, Schneider DH, Billstrand C, Pfaffinger D, Phillips N, Anderson RL, Philips B, Rajagopalan R, Hatsukami TS, Rieder MJ, Heagerty PJ, Nickerson DA, Abney M, Marcovina S, Jarvik GP, Scanu AM, Nicolae DL. Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q. J Lipid Res. 2009 May;50(5):798-806. doi: 10.1194/jlr.M800515-JLR200. Epub 2009 Jan 5.

    PubMed 19124843

  • Tada H, Takamura M, Kawashiri MA. Lipoprotein(a) as an Old and New Causal Risk Factor of Atherosclerotic Cardiovascular Disease. J Atheroscler Thromb. 2019 Jul 1;26(7):583-591. doi: 10.5551/jat.RV17034. Epub 2019 Apr 30.

    PubMed 31061262

  • Machado-Silva W, Alfinito-Kreis R, Carvalho LS, Quinaglia-E-Silva JC, Almeida OL, Brito CJ, Ferreira AP, Cordova C, Sposito AC, Nobrega OT; Brasilia Heart Study Group. Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction. Gene. 2015 Sep 1;568(2):165-9. doi: 10.1016/j.gene.2015.05.042. Epub 2015 May 20.

    PubMed 26002446

  • Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A, Haydock S, Hopper RV, Stephens NG, O'Shaughnessy KM, Brown MJ. A common variant of the endothelial nitric oxide synthase (Glu298-->Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999 Oct 5;100(14):1515-20. doi: 10.1161/01.cir.100.14.1515.

    PubMed 10510054

  • Zigra AM, Rallidis LS, Anastasiou G, Merkouri E, Gialeraki A. eNOS gene variants and the risk of premature myocardial infarction. Dis Markers. 2013;34(6):431-6. doi: 10.3233/DMA-130987.

    PubMed 23594558

Questions about this trial

What is this clinical trial studying?

A study testing Alirocumab and Evolocumab in people with Acute Coronary Syndrome and Premature Coronary Heart Disease, run by University Medical Centre Ljubljana at 1 site in Slovenia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Miran Šebeštjen, prof. (+38615228541, miran.sebestjen@guest.arnes.si, miran.sebestjen@kclj.si), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04613167, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in