Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS

NCT05624658 | Unknown DMC

• 1 other identifier: SamaraRCD-1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The study is prospective, open-label, randomized, single-center study involving patients admitted on an emergency basis with an acute coronary syndrome (ACS) clinic who underwent PCI of an infarct-related artery (IRA) and had intermediate coronary artery lesions (50-70% stenosis diameter) and elevated LDL-C ( \> 1.4 mmol/l) despite statin therapy at the highest dosage. Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day.

Conditions

Dyslipidemias

Keywords

acute coronary syndrome; PCI; plaque vulnerability; combined lipid-lowering therapy; PCSK9 inhibitors; Ezetimibe; coronary artery computed tomography

Outcome Measures

Primary Outcomes (1)

• Percent of change plaque vulnerability parameters on CCTA data

  change plaque vulnerability parameterson coronary artery computed tomography in non-IRA coronary arteries (positive remodeling; the presence of a low-density area in the plaque (less than 30 HU \*); point calcifications in the composition of the plaque; ring-shaped enhancement of X-ray density along the periphery of the plaque, not exceeding 130 HU, or the phenomenon of "circular glow")

  52 weeks

Secondary Outcomes (9)

• The number of participants with death, stent thrombosis/restenosis, nonfatal MI, hospitalization due to unstable angina, revascularization within 1 year

  52 weeks

• Total cholesterol, LDL-C, HDL-C, triglycerides levels after 52 weeks

  52 weeks

• dynamics of level hs-Troponin I within 1 year (ng/l)

  52 weeks

• dynamics of level hs-CRP within 1 year (mg/l)

  52 weeks

• dynamics of level NLR within 1 year

  52 weeks

Study Arms (2)

PCSK9 inhibitors in combination Atorvastatin at a dose of 80 mg /Rosuvastatin 40 mg/ day

ACTIVE COMPARATOR

Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg./ Rosuvastatin 40 mg / day.

Combination Product: Combined Lipid-lowering Therapy

Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/ day.

ACTIVE COMPARATOR

Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/day.

Combination Product: Combined Lipid-lowering Therapy

Interventions

Combined Lipid-lowering Therapy COMBINATION_PRODUCT

the effect of high-dose combined lipid-lowering therapy (statins+ezetimibe vs statins+PCSK9 inhibitors) on the vulnerability characteristics of atherosclerotic plaques assessed using multimodal imaging (coronary artery computed tomography and optical coherence tomography), as well as biomarkers in patients with acute coronary syndrome for 52 weeks.

Also known as: invasive coronary angiography, coronary artery commputed tomography, OCT, CAVI index

Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/ day.; PCSK9 inhibitors in combination Atorvastatin at a dose of 80 mg /Rosuvastatin 40 mg/ day

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• gender (any);
• age 18-75 years;
• admission \< 24 hours after pain onset
• acute coronary syndrome with at least one coronary artery stenosis requiring PCI;
• one or two non-IRA (coronary artery lumen diameter according to CAG \>20% and \<50% and no need for revascularization within the next 6 months according to the investigator)
• not taking statins for at least 3 (6) months or not achieving the target level of LDL-C at admission
• failure to achieve the target level of LDL-C ≥1.4 mmol/l on the second visit;
• signed informed consent

You may not qualify if:

• previous MI
• history of revascularization (PCI/CABG)
• presence of non-IRA stenoses ≥50%.
• multivessel lesion, including significant stenosis of the LM
• EF \< 40%,
• Killip III-IV.
• NYHA III-IV
• significant calcification or tortuosity of the coronary arteries, limiting OCT
• intolerance to statins, aspirin, P2Y12 inhibitors
• patients who have previously received PCSK9 inhibitors and/or Ezetimib
• treatment with systemic steroids or systemic cyclosporine within the last 3 months
• collagenoses and inflammatory diseases,
• oncological diseases within the last 5 years,
• scheduled surgery within 3 months
• persons suffering from mental disorders

Sponsors & Collaborators

• Samara Regional Cardiology Dispensary: lead
• Samara State Medical University: collaborator

Study Sites (1)

Samara Regional Cardiology Dispansery

Samara, 443070, Russia

RECRUITING

MeSH Terms

Conditions

Dyslipidemias; Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Dmitry Duplyakov

  Samara State Medical Universiry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dmitry Duplyakov, professor

CONTACT

+79277297273; duplyakov@yahoo.com

Anna Kovalskaya

CONTACT

+79270130848; kovalskaya.an@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Model Details: Patients who did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day. Also, on the 2nd visit, patients will undergo CCTA, an assessment of the CAVI index and a laboratory tests (blood count, lipid profile, ALAT, ASAT, Troponin I, Galectin -3, MMP -9, TIMP -1, high-sensitivity CRP, NGAL ). Every 3 months a visit is planned according to the schedule to monitor the effectiveness (blood count, ALAT, ASAT, lipid profile). Follow-up period will be 52 weeks, according to the schedule of visits. At the final visit, patients will undergo CCTA, assess the CAVI index and laboratory tests (blood count, lipid profile, Troponin I, Galectin-3, MMP-9, TIMP-1, high-sensitivity CRP, NGAL).

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 22, 2022
• Study Start: September 2, 2022
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)