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

Phase 4

Recruiting

• Conditions: In-stent Restenosis; Major Adverse Cardiovascular Events
• Interventions: Drug: PCSK9 inhibitor; Drug: Statin

• Registration Number: NCT05623995
• Lead Sponsor: Lin Zhao

Brief Summary

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).

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 Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-13
• Study First Posted: 2022-11-21
• Study Start: 2022-12-15
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-09
• Last Update Posted: 2023-11-13
• Primary Completion: 2024-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	PCSK9 inhibitor	Participants will receive PCSK9 inhibitors added to guideline recommended statin therapy.
Control arm	Statin	Patients will continue to taking guideline recommended statin therapy.

Primary Outcome Measures

Name	Time	Method
Change in percent plaque volume and plaque burden.	12 months	Change in percent plaque volume and plaque burden by intravascular ultrasound (IVUS) between PCSK9 inhibitors group and control group.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beijing Anzhen Hospital; 🇨🇳 Beijing, Beijing, China