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

NCT06586684 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: EICP-UCG
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carotid Plaque; Hyperlipidemia; Echocardiography

Keywords

inclisiran; carotid plaque; Echocardiography; hyperlipidmia

Outcome Measures

Primary Outcomes (5)

• CIMT

  Carotid artery intima media thickness

  Immediately and treated with inclisiran one year later

• TMPT

  The maximal plaque thickness

  Immediately and treated with inclisiran one year later

• CPA

  Carotid plaque area

  Immediately and treated with inclisiran one year later

• CPV

  Carotid plaque volume

  Immediately and treated with inclisiran one year later

• CALA

  Carotid artery lumen area

  Immediately and treated with inclisiran one year later

Study Arms (1)

inclisiran Therapy group

EXPERIMENTAL

Patients with carotid plaques undergoing treatment with inclisiran

Drug: Inclisiran

Interventions

Inclisiran DRUG

Patients with carotid plaques undergoing treatment with inclisiran

inclisiran Therapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• First Affiliated Hospital of Xinjiang Medical University: lead

Related Publications (11)

• 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.

  PMID: 32187462 BACKGROUND

• 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.

  PMID: 33663735 BACKGROUND

• 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.

  PMID: 38371290 BACKGROUND

• 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.

  PMID: 31621834 BACKGROUND

• 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.

  PMID: 23247808 BACKGROUND

• 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.

  PMID: 31630870 BACKGROUND

• 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.

  PMID: 17384434 BACKGROUND

• 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.

  PMID: 36967822 BACKGROUND

• 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.

  PMID: 36331315 BACKGROUND

• 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.

  PMID: 36686711 BACKGROUND

• 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.

  PMID: 33893754 BACKGROUND

MeSH Terms

Conditions

Hyperlipidemias

Interventions

ALN-PCS

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Zhenyan Fu, PhD

  First Affiliated Hospital of Xinjiang Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuanhao Yao, MD

CONTACT

09914366872; yyh991012@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pricinple Inverstigator

Study Record Dates

• First Submitted: September 1, 2024
• First Posted: September 19, 2024
• Study Start: September 20, 2024
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share