Functional Improvement of Coronary Artery Narrowing by Cholesterol Reduction With a PCSK9 Antibody

NCT04141579 | Completed

• 1 other identifier: NL71538.091.19
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

In a large number of patients who experienced an acute coronary syndrome, multiple narrowings of the coronary arteries are identified. Mechanical treatment of the infarct related artery is indisputable, yet mechanical treatment of other bystander lesions in non-infarct related arteries is controversial. Low-density lipoprotein cholesterol can speed up the formation of these coronary artery narrowings, and can increase the risk of a second event. The investigators want to investigate if treating patients with the new cholesterol-lowering drug evolocumab in addition to statin therapy ameliorates blood flow and reduces atherosclerotic plaque size compared with placebo. Improved blood flow and a reduction of plaque size could prevent the need for additional stenting or surgery.

Conditions

Coronary Artery Disease; Atherosclerosis of Coronary Artery

Outcome Measures

Primary Outcomes (2)

• Change in FFR from baseline to follow-up in non-IRA lesions.

  Primary physiological endpoint

  FFR will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

• Change in lipid core burden index at the 4mm maximal segment (MaxLCBI4mm) from baseline to follow-up of the non-IRA.

  Primary imaging endpoint

  LCBI will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

Secondary Outcomes (4)

• The change in percent atheroma volume (PAV, %)

  IVUS will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

• The change in normalized total atheroma volume (TAV, mm3)

  IVUS will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

• The change in maximum plaque burden (PB, %)

  IVUS will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

• The change in minimum luminal area (MLA, mm2)

  IVUS will be assessed at baseline (0 weeks) and at the last follow-up visit (12 weeks)

Other Outcomes (6)

• The correlations between achieved on-treatment LDL-C, the change in FFR, the change in LCBI and the change in PAV

  This endpoint is measured at the last study visit (12 weeks)

• The correlation between baseline NIRS derived MaxLCBI4mm and change in FFR of the non-IRA.

  This endpoint is measured at the last study visit (12 weeks)

• The correlation between change in IVUS-derived plaque characteristics and change in FFR of the non-IRA

  This endpoint is measured at the last study visit (12 weeks)

Study Arms (2)

Treatment arm

EXPERIMENTAL

Evolocumab (140mg) will be administered subcutaneously every two weeks (Q2W) on day 1 through week 12 with personal injectors, containing 1 mL deliverable volume of 140 mg/mL Evolocumab.

Drug: Evolocumab 140 MG/ML [Repatha]

Comparator arm

PLACEBO COMPARATOR

Placebo will be administered subcutaneously every two weeks (Q2W) on day 1 through week 12 with personal injectors, containing 1 mL deliverable volume of placebo.

Drug: Placebo

Interventions

Evolocumab 140 MG/ML [Repatha] DRUG

Evolocumab (also known as Repatha, formerly referred to as AMG 145) is a human monoclonal immunoglobulin G2 (IgG2) that specifically binds to proprotein convertase subtilisin/kexin type 9 (PCSK9) preventing its interaction with the low-density lipoprotein receptor (LDLR). The inhibition of PCSK9 by evolocumab leads to increased LDLR expression and subsequent decreased circulating concentrations of low-density lipoprotein cholesterol (LDL-C).

Also known as: AMG145, Repatha

Treatment arm

Placebo DRUG

Matching placebo

Also known as: Placebo injection

Comparator arm

Eligibility Criteria

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

You may qualify if:

• ACS with PCI of infarct related artery
• MVD
• FFR of non-IRA lesion 0.67 - 0.85
• years old at screening

You may not qualify if:

• Refusal or inability to provide informed consent
• Prior coronary artery bypass graft
• Known left ventricular ejection fraction (LVEF) \< 30%
• Untreated functional left main stem stenosis (FFR ≤ 0.80)
• Contra-indication for antithrombotic therapy according to ESC guidelines
• Non-IRA stenosis not amenable for PCI treatment (operator's decision)
• Complicated IRA treatment, with one or more of the following:
• Extravasation
• Permanent no re-flow after IRA treatment (TIMI flow 0-1)
• Inability to implant a stent
• Known severe cardiac valve dysfunction that will require surgery in the follow-up period.
• Severe kidney disease defined as an eGFR \< 30 ml/min.
• Known severe liver disease defined as Child-Pugh score of 10-15.
• Female subject is pregnant, breastfeeding or planning to become pregnant or planning to breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive serum pregnancy test.
• Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Amgen: collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (2)

• Mensink FB, Los J, Reda Morsy MM, Oemrawsingh RM, von Birgelen C, Ijsselmuiden AJJ, Meuwissen M, Cheng JM, van Wijk DF, Smits PC, Paradies V, van Wijk DJ, Rai H, Ten Cate TJF, Camaro C, Damman P, van Nunen LX, Dimitriu-Leen AC, van Wely MH, Cetinyurek-Yavuz A, Byrne RA, van Royen N, van Geuns RM. Changes in non-culprit coronary lesions with PCSK9 inhibitors: the randomised, placebo-controlled FITTER trial. EuroIntervention. 2025 Aug 18;21(16):910-920. doi: 10.4244/EIJ-D-24-01065.

  PMID: 40828313 DERIVED

• Mensink FB, Los J, Oemrawsingh RM, von Birgelen C, Ijsselmuiden A, Meuwissen M, Cheng JM, van Wijk DF, Smits PC, Paradies V, van der Heijden DJ, Rai H, Ten Cate TJ, Camaro C, Damman P, van Nunen LX, Dimitriu-Leen AC, van Wely MH, Cetinyurek-Yavuz A, Byrne RA, van Royen N, van Geuns RM. Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody: Rationale and design of the randomized FITTER trial. Heliyon. 2024 Sep 18;10(19):e38077. doi: 10.1016/j.heliyon.2024.e38077. eCollection 2024 Oct 15.

  PMID: 39430462 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Robert Jan van Geuns, MD, PhD

  robertjan.vangeuns@radboudumc.nl

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two arms. One treatment arm. One arm with placebo.

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: October 28, 2019
• Study Start: November 10, 2020
• Primary Completion: November 9, 2023
• Study Completion: November 9, 2023
• Last Updated: July 18, 2024

Record last verified: 2023-11

Locations

NL (1)