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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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In-stent Restenosis, Major Adverse Cardiovascular Events

Intervention / Treatment
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* Drug: PCSK9 inhibitor
* Drug: Statin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Neointimal volume with intravascular ultrasound (IVUS) (mm3 per 1mm) | Comparison of neointima volume by IVUS between PCSK9 inhibitors group and control group. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic total occlusion, Restenosis