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

Coronary Artery Disease Clinical Trial

Official title: Functional Improvement of Non-infarcT relaTed Coronary Artery Stenosis by Extensive LDL-C Reduction With a PCSK9 Antibody

Status Recruiting

Clinical Trial Summary

In a large number of patients who had a heart attack, multiple narrowings of the coronary arteries are identified. It is common practice to treat the narrowing that is the cause of the heart attack with a stent. It is not yet clearly known if the other narrowings in the other coronary arteries have to be treated immediately with a stent as well.

"Bad" cholesterol (LDL-cholesterol) can speed up the formation of these coronary artery narrowings, and can thus make the risk of a second heart attack bigger.

The investigators want to investigate if treating patients with the new cholesterol-lowering drug Evolocumab on top of the normal cholesterol lowering therapy (statins) ameliorates blood flow through coronary artery narrowings. Better blood flow through these narrowings could prevent the need for stenting or surgery in the future.

Clinical Trial Description

Rationale:

In a large number of patients presenting with acute coronary syndrome (ACS) multivessel disease (MVD) is identified. Optimal treatment approach for bystander lesions in non-infarct related arteries (non-IRA's) has not been well established. Multiple RCT's favor preventive percutaneous intervention (PCI) over medical treatment, however medical treatment wasn't optimal in these studies. Revascularization of lesions in the non-IRA can be guided by fractional flow reserve (FFR). The investigators want to investigate if optimizing LDL-C lowering therapy after an ACS has an effect on functional impairment of a non-IRA lesion and could thus prevent mechanical intervention (PCI or CABG).

Objective:

To evaluate the effect of maximal LDL-C reduction by Evolocumab on top of optimal background lipid-lowering therapy (ESC guidelines) on FFR of non-IRA lesions, in patients presenting with MVD-ACS.

Secondly to correlate baseline lipid core burden with changes in FFR and to investigate the relation between LDL-C reduction and change in pro-inflammatory monocyte phenotypes.

Study design: This is a multi-center, randomized, double blind, placebo controlled clinical trial.

Study population:

Patients presenting with MVD-ACS and eligible LDL-C levels will be included in this study. Patients must be 18 years or older. The investigators aim to include at least 150 patients to achieve adequate power for this study.

Intervention: The patients will be randomized 1:1 to (A), one group will receive 140mg Evolocumab every two weeks (Q2W) for 12 weeks, using personal injectors; (B) the other group will receive placebo. All participants will receive high intensity statin therapy (HIST) as background therapy (Atorvastatin 40mg or equivalent).

Main study parameters/endpoints:

The primary study parameter is the change in FFR from baseline to follow-up in non-IRA lesions. The secondary invasive imaging endpoint is the correlation between baseline Near-InfraRed Spectroscopy (NIRS) derived lipid core burden (MaxLCBI4mm) and change in FFR of the non-IRA.

The investigators will assess the index of microcirculatory resistance (IMR) as an exploratory endpoint.

Main endpoint for the immunological parameters is the comparison of monocyte phenotype between the groups at t=12 weeks post-ACS.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

After inclusion, all patients have to undergo staged FFR + NIRS, meaning they will undergo invasive strategy for a second time, and if needed additional stenting of significant lesions, with the associated periprocedural risks (e.g. death, stroke, myocardial infarction (MI), vascular complications), however these risks are quite small (<2% major complications) . ;

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerosis of Coronary Artery
• Coronary Artery Disease
• Myocardial Ischemia

• NCT number: NCT04141579
• Study type: Interventional
• Source: Radboud University Medical Center
• Contact: Frans B Mensink, MD, MSc
• Phone: (0) 24 3092476
• Email: frans.mensink@radboudumc.nl
• Status: Recruiting
• Phase: N/A
• Start date: February 11, 2020
• Completion date: June 2023