Optimal Predilatation Treatment Before Implantation of a Magmaris Bioresorbable Scaffold in Coronary Artery Stenosis

Study Overview
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Brief Summary
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The aim of the study is to investigate if lesion preparation with a ScoreFlex balloon compared to a standard non-compliant balloon improve vascular healing and minimize lumen reduction after implantation of a Magmaris bioresorbable scaffold.

Detailed Description
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Introduction: Ischemic heart disease (IHD) is characterized by progressive atherosclerosis in coronary arteries and may cause coronary artery stenosis or acute thrombus and occlusion. IHD is often treated with percutaneous coronary intervention (PCI) with balloon dilatation and implantation of a stent. The drug-eluting stents (DES) have been developed to minimize neointimal growth after implantation and reduce the risk of in-stent restenosis compared to bare-metal stents (BMS). Newer devices, bioresorbable scaffold (BRS), are made from a bioresorbable material slowly dissolving after implantation. The BRS guarantees optimal vessel support after balloon dilatation and implantation, but the artery can obtain original function and flexibility after the BRS has vanished. The development of the Magmaris BRS, with its improved radial strength, thinner struts compared to previous BRSs, is developed to reduce the complications seen in earlier generation BRS such as recoil, fracture and late stent thrombosis. Previous studies have shown that coronary lesions treated with the previous generation of the Magmaris BRS resulted on lumen area reduction, possibly a consequence by increased plaque burden, compromising the scaffold area, combined with increased neointimal formation in the early phase of vascular healing and fast resolution. Due to decreased radial strength of the BRS compared to metal stents, modification of plaque prior to BRS-implantation is necessary. The ScoreFlex balloon is a non-compliant balloon with circumference of fixated, scoring elements and permits controlled expansion and fragmentation of calcified plaque, compared to standard treatments with a non-compliant balloon. Intravascular imaging with Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) can assess the morphology and location of plaques in the coronary stenosis prior to PCI thereby optimizing the implantation. The scaffold-treated segment can also be evaluated with intravascular imaging components such as stent coverage, malapposition and neointimal hyperplasia, but only if the scaffold is visible. If the scaffold is dissolved, another method to assess the vascular healing is needed. IVUS can evaluate change in elastic external membrane (EEM), change in remodeling and minimal lumen area (MLA). The reduction in MLA is associated with increased neointimal hyperplasia and plaque burden in the vessel wall. The aim of the study is to investigate if lesion preparation with a ScoreFlex balloon compared to a standard non-compliant balloon improve vascular healing and minimize lumen reduction after implantation of a Magmaris bioresorbable scaffold. Method: The study is designed as a prospective randomized trial conduced at a single center (Odense University Hospital, Denmark). Eighty-two patients with stable angina pectoris and non-ST-segment elevation myocardial infarctions are included, if they meet the criteria. Pre-dilatation with a 2.0 mm balloon is performed followed by pre-interventional IVUS and OCT. Patients are randomized to lesion preparation and pre-dilatation with either the ScoreFlex balloon or a standard non-compliant balloon with a 1:1 balloon-to-artery ratio by measuring the reference segments. The residual stenosis should be less than 20 %. If the pre-dilatation goal is not achieved, up-scaling to a balloon 0,5 mm larger is allowed. The lesion is treated with implantation of a Magmaris scaffold. Finally, IVUS and OCT-images of the final result are obtained. Follow-up IVUS and OCT images are performed after 6 and 12 months. Post-PCI OCT-images are analyzed at baseline and 6 and 12 months after index procedure. Change in MLA in the stented segment is measured with IVUS and OCT. The vascular healing is based on finding from the OCT images. The study is submitted and approved by the Regional Committees on Health Research Ethics for Southern Denmark (Project-ID: S-20200114) and Danish Data Agency (Journal nr.: 20/49900) Statistics: Assuming data are normally distributed, categorical data will be presented as numbers and frequencies and compared using chi2-test. Continuous data will be presented as mean ± SD and compared using Student t-test- SPSS version 26.0 will be used for the statistical analysis. The estimated sample size is based on data, from the HONEST study by Fallesen et al. The reduction of MLA from 6.99 mm2 to 5.01 mm (27%) 6 months after implantation of a Magmaris BRS, represented the expected reference group. Optimal lesion preparation with pre-dilatation with a ScoreFlex balloon is estimated to minimize MLA reduction from 6.99 mm2 to 6.22 mm2 (11%). A power calculation is conducted using the expected MLA after 6 months (6.22 mm2 for the ScoreFlex balloon and 5.01 mm2 for the standard non-compliant balloon). Inclusion of 35 patients in each group is necessary to reach statistical significance in case of 2-tailed significance level of 0.05 and power of 80 %. Loss to follow-up and poor image quality finalize an expected drop-out rate of 15 %, thereby requiring 82 patients in total.

Official Title
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Optimal Predilatation Treatment Before Implantation of a Magmaris Bioresorbable Scaffold In Coronary Artery Stenosis

Conditions
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Coronary Artery Stenosis, Myocardial Infarction, Cardiovascular Diseases, Myocardial Ischemia, Atherosclerosis of Artery, Coronary Disease, Heart Diseases, Coronary Artery Disease, Stable Angina, Arterial Occlusive Diseases

Intervention / Treatment
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* Device: ScoreFlex balloon
* Device: Device: standard non-compliant balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stable angina pectoris and non-ST elevation myocardial infarction referred for invasive coronary angiography and percutaneous coronary intervention at Department of Cardiology, Odense University Hospital (Odense, Denmark) Exclusion Criteria: participation in other randomized clinical trials life expectancy < 1 year allergy to aspirin, clopidogrel, ticagrelor or prasugrel eGFR < 30 mL/min tortuous and angiographically estimated extremely calcified lesions ostial, left main and bifurcation lesions lesions in a reference vessel diameter < 2.0 mm hemodynamic instability scheduled for coronary artery bypass grafting

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
Interventional Model Description: Eligible patients randomized to predilatation with ScoreFlex balloon or a standard non-compliant balloon before percutaneous coronary intervention with implantation of a Magmaris bioresorbable scaffold.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ScoreFlex balloon<br>Pre-dilatation with a ScoreFlex balloon before implantation with a Magmaris bioresorbable scaffold | Device: ScoreFlex balloon<br>* Pre-dilatation with a ScoreFlex balloon<br>|
| Active Comparator: Standard non-compliant balloon<br>Pre-dilatation with a non-compliant balloon before implantation with a Magmaris bioresorbable scaffold | Device: Device: standard non-compliant balloon<br>* Pre-dilatation with a standard non-compliant balloon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal Lumen Area | Minimal Lumen Area | 6 months after index percutaneous coronary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in remodeling Index | Change in remodeling Index | 6 months and 12 months after index percutaneous coronary intervention | 
| Change in Minimal Lumen Area | Change in Minimal Lumen Area | 6 months and 12 months after index percutaneous coronary intervention | 
| Percentage of incomplete scaffold apposition | Percentage of incomplete scaffold apposition | 6 months and 12 months after index percutaneous coronary intervention | 
| Percentage of uncovered struts | Percentage of uncovered struts | 6 months and 12 months after index percutaneous coronary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioresorbable scaffolds, optical coherence tomography, intravascular ultrasound, modified balloons