Effect of Small Interfering RNA Inclisiran on Carotid Plaques As Assessed by Carotid Ultrasound

NCT ID: NCT06586684

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-20
• Study Completion Date: 2026-09-30

Brief Summary

Current understanding suggests that the majority of cardiovascular events are driven by vulnerable plaques. Nonetheless, the impact of PCSK9 inhibitors on the stability of carotid plaques remains insufficiently elucidated, with a notable scarcity of relevant clinical studies. This investigation seeks to address this gap through a real-world study conducted among patients with arterial sclerosis in Asia. The primary aim is to evaluate the effects of small interfering RNA (inclisiran) on carotid plaque characteristics as assessed by ultrasound, thereby contributing valuable data to inform clinical practice.

Detailed Description

In a meticulous study evaluating the impact of inclisiran on patients with atherosclerosis and carotid plaques, data were systematically gathered across multiple time points. The assessment encompassed:Blood Samples: Analyzed at baseline (Month 0) and subsequently at Months 1, 2, 3, 5, 9, 11, and 12, examining biochemical markers, lipid profiles, and liver and kidney function tests.Carotid Ultrasound: Conducted at Months 0, 3, 9, and 12, monitoring the carotid intima-media thickness, maximum carotid plaque thickness, carotid plaque area, carotid plaque volume, and carotid lumen stenosis area for thorough analysis.Clinical Records: Documented in detail the baseline clinical information, biochemical markers, imaging findings, and any adverse cardiovascular or cerebrovascular events that occurred throughout the study period. This approach ensures a comprehensive understanding of inclisiran's effects over time, encompassing both biochemical and imaging parameters, while tracking potential adverse events.

Conditions

Carotid Plaque; Hyperlipidemia; Echocardiography

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

inclisiran Therapy group

Patients with carotid plaques undergoing treatment with inclisiran

Group Type: EXPERIMENTAL

Inclisiran

Intervention Type: DRUG

Patients with carotid plaques undergoing treatment with inclisiran

Interventions

Inclisiran

Patients with carotid plaques undergoing treatment with inclisiran

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with carotid plaques as indicated by ultrasound
• Men and women aged 18-75 years;
• LDL-C >3.4 mmol/L without regular statin therapy or LDL-C >1.8 mmol/L after 4 weeks of statin lipid-lowering therapy.

Exclusion Criteria

• - Known allergies or contraindications to PCSK9 inhibitors and/or statin therapy;
• Prior use of PCSK9 inhibitors;
• Prior history of hemorrhagic stroke;
• Prior coronary artery bypass grafting or coronary intervention;
• Inability to perform OCT imaging or unclear imaging;
• Severe renal insufficiency (creatinine clearance < 30 mL/min);
• Severe hepatic dysfunction;
• Baseline triglycerides > 5.6 mmol/L;
• Pregnant or lactating women;
• Life expectancy not exceeding 1 year;
• In the judgment of the investigator, unsuitable for this study for any reason.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Xinjiang Medical University

OTHER

Sponsor Role: lead

Responsible Party

Zhenyan Fu, PHD

Pricinple Inverstigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhenyan Fu, PhD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Xinjiang Medical University

Central Contacts

Yuanhao Yao, MD

Role: CONTACT

yyh991012@outlook.com

09914366872 ext. +86

References

Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, Leiter LA, Kastelein JJP, Ray KK, Kallend D. Effects of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clin Proc. 2020 Jan;95(1):77-89. doi: 10.1016/j.mayocp.2019.08.021. Epub 2019 Oct 17.

Reference Type: BACKGROUND

PMID: 31630870 (View on PubMed)

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, Grobbee DE, Bots ML; METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007 Mar 28;297(12):1344-53. doi: 10.1001/jama.297.12.1344. Epub 2007 Mar 25.

Reference Type: BACKGROUND

PMID: 17384434 (View on PubMed)

Wu L, Kong Q, Huang H, Xu S, Qu W, Zhang P, Yu Z, Luo X. Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study. Front Aging Neurosci. 2023 Mar 9;15:1127534. doi: 10.3389/fnagi.2023.1127534. eCollection 2023.

Reference Type: BACKGROUND

PMID: 36967822 (View on PubMed)

Ray KK, Kallend D, Leiter LA, Raal FJ, Koenig W, Jaros MJ, Schwartz GG, Landmesser U, Garcia Conde L, Wright RS; ORION-11 Investigators. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J. 2022 Dec 21;43(48):5047-5057. doi: 10.1093/eurheartj/ehac615.

Reference Type: BACKGROUND

PMID: 36331315 (View on PubMed)

Wong EY, Nikolov HN, Rankin RN, Holdsworth DW, Poepping TL. Evaluation of distal turbulence intensity for the detection of both plaque ulceration and stenosis grade in the carotid bifurcation using clinical Doppler ultrasound. Eur Radiol. 2013 Jun;23(6):1720-8. doi: 10.1007/s00330-012-2741-6. Epub 2012 Dec 18.

Reference Type: BACKGROUND

PMID: 23247808 (View on PubMed)

Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.

Reference Type: BACKGROUND

PMID: 32187462 (View on PubMed)

Wright RS, Ray KK, Raal FJ, Kallend DG, Jaros M, Koenig W, Leiter LA, Landmesser U, Schwartz GG, Friedman A, Wijngaard PLJ, Garcia Conde L, Kastelein JJP; ORION Phase III Investigators. Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis. J Am Coll Cardiol. 2021 Mar 9;77(9):1182-1193. doi: 10.1016/j.jacc.2020.12.058.

Reference Type: BACKGROUND

PMID: 33663735 (View on PubMed)

Huo Y, Lesogor A, Lee CW, Chiang CE, Mena-Madrazo J, Poh KK, Jeong MH, Maheux P, Zhang M, Wei S, Han Y, Li Y. Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18. JACC Asia. 2023 Nov 14;4(2):123-134. doi: 10.1016/j.jacasi.2023.09.006. eCollection 2024 Feb.

Reference Type: BACKGROUND

PMID: 38371290 (View on PubMed)

Mantella LE, Colledanchise KN, Hetu MF, Feinstein SB, Abunassar J, Johri AM. Carotid intraplaque neovascularization predicts coronary artery disease and cardiovascular events. Eur Heart J Cardiovasc Imaging. 2019 Nov 1;20(11):1239-1247. doi: 10.1093/ehjci/jez070.

Reference Type: BACKGROUND

PMID: 31621834 (View on PubMed)

Chen J, Zhao F, Lei C, Qi T, Xue X, Meng Y, Zhang W, Zhang H, Wang J, Zhu H, Cheng C, Wang Q, Bi C, Song B, Jin C, Niu Q, An F, Li B, Huo X, Zhao Y, Li B. Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study. Front Pharmacol. 2023 Jan 4;13:999224. doi: 10.3389/fphar.2022.999224. eCollection 2022.

Reference Type: BACKGROUND

PMID: 36686711 (View on PubMed)

Aranzulla TC, Piazza S, Ricotti A, Musumeci G, Gaggiano A. CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study. Catheter Cardiovasc Interv. 2021 Jul 1;98(1):E115-E121. doi: 10.1002/ccd.29743. Epub 2021 Apr 24.

Reference Type: BACKGROUND

PMID: 33893754 (View on PubMed)

Other Identifiers

EICP-UCG

Identifier Type: -

Identifier Source: org_study_id