Effect of Evolocumab on Chronic Total Occlusions (EVOLO-CTO)

Effect of Evolocumab on Chronic Total Occlusions After Successful Percutaneous Coronary Intervention (EVOLO-CTO)

The purpose of this study is to evaluate the effect of proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors added to regular statin therapy on target lesion failure (TLF) and arteriosclerosis progression in patients with chronic total occlusions (CTOs) undergoing successful percutaneous coronary intervention (PCI).

Study Overview

• Status: Recruiting
• Conditions: In-stent Restenosis; Major Adverse Cardiovascular Events
• Intervention / Treatment: Drug: PCSK9 inhibitor; Drug: Statin

Detailed Description

Chronic total occlusions (CTOs) are found in 15-25% of patients with stable angina pectoris. The presence of a CTO indicates unfavorable prognosis, with higher rate of major adverse cardiovascular events. Statins are frequently used after PCI in order to lower LDL cholesterol levels and reduce the chances of coronary artery obstruction recurring. Despite this preventive measure, high risk for restenosis and re-occlusion was observed a significant proportion of patients with CTOs undergoing PCI.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors represent a novel class of lipid-lowering drugs leading to rapid, profound, and consistent reductions in LDL-C levels. The effect of PCSK9 inhibitor in patients with CTO, after a recent PCI is not known.

In this study the investigators want to evaluate the effect of the PCSK9 inhibitor on neointimal hyperplasia and target lesion failure (TLF) in patients with CTOs receiving regular statin treatment. A serial of intravascular ultrasound imaging study will be performed to determine the arteriosclerosis progression at 48 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xu Wang, MD; Phone Number: +8615311765609; Email: huaianwangxu@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Recruiting
      • Beijing Anzhen Hospital
      • Contact: Xu Wang, MD; Phone Number: +86 15311765609; Email: huaianwangxu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age with written informed consent
• Presence of a CTO in native coronary artery.
• Stable angina or myocardial ischemia in a territory supplied by CTO
• CTO located in segments 1-3 (RCA), 6-7 (LAD), 11-12 (LCx)
• Target artery ≥2.5mm
• Scheduled to undergo percutaneous coronary intervention (PCI)
• LDL-C ≥70 mg/dL (≥1.8 mmol/L) in patients who have been on any stable statin regimen for ≥ 4 weeks prior to enrollment; or LDL-C ≥125 mg/dL (≥3.2 mmol/L) in patients who are statin-naïve or have not been receiving stable statin regimen for ≥ 4 weeks prior to enrollment

Exclusion Criteria:

• Acute myocardial infarction within 1 month
• Known severe chronic kidney disease (estimated Glomerular Filtration Rate [eGFR] <60 mL/min/1.73m2 or serum creatinine level >2.5 mg/dL);
• History of allergy to iodine contrast agents
• Allergy to PCSK9 inhibitors or any other ingredients contained in study drug
• Pregnancy or breastfeeding
• Persistent or permanent atrial fibrillation
• Patients with history of coronary artery bypass graft
• Inability or unwilling to provide informed consent
• Malignant neoplasms or Major illness with life expectancy <1 year
• Planned coronary revascularization or major non-cardiac surgery 12 months after intervention
• Patients previously treated with PCSK9 inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; Participants will receive PCSK9 inhibitors added to guideline recommended statin therapy.	Drug: PCSK9 inhibitor; Evolocumab per every two weeks, starting at day 1 and up to week 48, added to guideline recommended statin therapy..; Other Names: Evolocumab
Active Comparator: Control arm; Patients will continue to taking guideline recommended statin therapy.	Drug: Statin; Guideline recommended statin therapy.; Other Names: Hydroxymethylglutaryl-Coenzyme A Reductase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in percent plaque volume and plaque burden.	Change in percent plaque volume and plaque burden by intravascular ultrasound (IVUS) between PCSK9 inhibitors group and control group.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neointimal volume with intravascular ultrasound (IVUS) (mm3 per 1mm)	Comparison of neointima volume by IVUS between PCSK9 inhibitors group and control group.	12 months
Rate of Target Lesion Failure (TLF)	TLF is defined as a composite of: all cardiac death, target vessel myocardial infarction (SCAI definition), and clinically driven target lesion revascularization (TLR).	12 months
Ischemia	Ischemic burden assessed with CMR from baseline to 3 and 12 months follow-up	12 months
Change in left ventricular systolic function assessed with CMR	The left ventricular ejection fraction assessed with CMR from baseline to 3 and 12 months follow up	12 months

Collaborators and Investigators

• Sponsor: Lin Zhao
• Investigators: Principal Investigator: Lin Zhao, MD, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 13, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Restenosis; Chronic total occlusion
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Serine Proteinase Inhibitors; Evolocumab; Hydroxymethylglutaryl-CoA Reductase Inhibitors; PCSK9 Inhibitors
• Other Study ID Numbers: 2022-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No