SOLVE-ACS: Bioresorbable Magnesium-Stents Magmaris in ACS Lesions

Study Overview
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Brief Summary
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The aim of the registry is to investigate the clinical performance of the Magmaris Magnesium Stent in STE-ACS and NSTE-ACS patients.

Detailed Description
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The Magmaris Magnesium-Stent is indicated for improving luminal diameter and stabilize culprit lesions in patients with coronary artery disease (CAD) including ST-segment elevation (STE-) as well as Non-ST-segment elevation (NSTE-) acute coronary syndrome (ACS). Patients scheduled for this registry, must have one angiographic clear detectable ACS-causing culprit lesion with a reference diameter and a lesion length, which closely match the nominal Magmaris reference diameter and length. Primary endpoint will be the procedural angiographical success at the end of PCI, defined as successful Magmaris implantation at the culprit lesion site with less than 30% final stenosis (by visual estimation) and distal TIMI 3 flow. Secondary endpoints will include clinical and angiographic parameters as well as parameters gained through OCT-imaging.

Official Title
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SOLVE-ACS: Prospective Multicenter Evaluation of the Performance of the Bioresorbable Magnesium-Stents Magmaris in Patients With Acute Coronary Syndrome (ACS)

Conditions
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Acute Coronary Syndrome, STEMI - ST Elevation Myocardial Infarction, NSTEMI - Non-ST Segment Elevation MI

Intervention / Treatment
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* Device: Implantation of the Magmaris scaffold


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients of 18 - 70 years of age STE- or NSTE-ACS with planned invasive therapy strategy At least coronary one-vessel disease with one angiographically detectable culprit lesion Target lesion length ≤ 21 mm and its diameter is ≥ 2.7mm and ≤ 3.7 mm by QCA or by visual estimation. Subject is eligible for Dual Anti Platelet Therapy (DAPT) for 12 months after ACS Additional inclusion criteria MCG-substudy: Hospitalization for NSTE- ACS in low- and/or risk-class (GRACE-Score ≤ 170) with planned invasive therapy Exclusion Criteria: Currently participating within a FIM or RCT and primary endpoint is not reached yet. Known allergies to: Acetylsalicylic Acid (ASA), clopidogrel, ticlopidine, prasugrel, heparin or any other anticoagulant /antiplatelet required for PCI, contrast medium, sirolimus, or similar drugs or the Magmaris materials including Magnesium, Yttrium, Neodymium, Zirconium, Gadolinium, Dysprosium, Tantalum that cannot be adequately pre-medicated. Renal insufficiency with serum-creatinine ≥ 2.5 mg/dl or subjects on dialysis. Known systolic heart failure with left-ventricular ejection fraction (LV-EF≤ 30 %). Active sepsis. Presence of cardiogenic shock or heart failure requiring intubation, inotropes, intravenous diuretics or mechanical circulation support. Refractory ventricular arrhythmia requiring pharmacologic or defibrillator therapy. Patients under immunosuppressive therapy. Unprotected significant left main- stenosis. ACS with culprit lesion in a bypass graft or ACS caused by stent/BVS-thrombosis or stent/BVS-restenosis. ACS caused by left main coronary artery disease or an ostial target lesion (within 5.0 mm of vessel origin). Culprit lesion involves a side branch ≥2.0 mm in diameter (bifurcation lesion). Culprit lesion located within a true vessel bifurcation (including side branch > 2mm) which requires bifurcation-treatment according to the investigator's discretion. Extent and severity of CAD is such that investigator believes it is likely that bypass surgery will be required within 1 year of enrollment. Severe calcification or extreme tortuosity of vessel with culprit lesion. Culprit lesion with very distal location. Culprit vessels with low or no-reflow phenomenon (TIMI 0,I,II) after mechanical recanalization or pre-dilatation using a non-compliant balloon with 1:1 balloon-to-artery ratio. Culprit lesions with a length ≥ 21 mm or within vessels with reference diameter≤ 2.7mm or ≥ 3.7 mm by QCA or by visual estimation. Unsuccessful pre-dilatation, defined as minimal lumen diameter smaller than the respective crossing profile of Magmaris and angiographic complications (e.g. distal embolization, side branch closure, extensive dissections), by visual estimation. Additional exclusion criteria MCG-substudy: Non-MCG-safe metal implants Inability or unwillingness to lie flat for 5 minutes and follow breathing commands

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Magmaris implantation<br>Subjects will undergo a PCI for the implantation of the Magmaris scaffold in accordance with the standard of care and standard hospital practice. | Device: Implantation of the Magmaris scaffold<br>* Subjects will undergo a PCI for the implantation of the Magmaris scaffold in accordance with the standard of care and standard hospital practice. Maximum of one single ACS-causing de novo lesions in one separate major epicardial vessels is allowed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedural angiographical success | Procedural angiographical success at the end of PCI, defined as successful Magmaris implantation at the culprit lesion site with less than 30% final stenosis (by visual estimation) and distal TIMI 3 flow. | At the end of PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ST-segment resolution at the electrocardiogram (ECG) | ST-segment resolution at ECG. | Within 60 minutes of primary PCI | 
| Procedural clinical success within hospital stay | No in-hospital clinically-driven target lesion revascularization. | Until hospital discharge, an expected average of 4 days | 
| Target lesion revascularization | Clinical driven target-lesion revascularization with the use of either PCI or CABG at 6 months, 12 months and at 2 years follow-up respectively. | 6 months, 12 months and 2 years | 
| Device-oriented composite endpoint (DOCE) | Device-oriented composite (DOCE) endpoint of cardiac death, target vessel-related reinfarction and ischemia-driven target-lesion revascularization at 6 months, 12 months and at 2 years follow-up respectively. | 6 months, 12 months and 2 years | 
| Major adverse cardiovascular events (MACE) | Cardiac death, any TV-MI, target vessel revascularization (TVR) in-hospital or during follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| All-cause death at all time points | Clinical Endpoint (in-hospital and at follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| Cardiac death at all time points | Clinical Endpoint (in-hospital and at follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| Magmaris Thrombosis | Any definite/probable per ARC defintion Magmaris thrombosis (in-hospital and during follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| Any Bleeding | Bleedings defined according to the Bleeding Academic Research Consortium (BARC) in-hospital and at follow-up (in-hospital and at follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| Vascular cerebral events | Vascular events documented by neurological permanent disabilities or by diagnostic imaging (MRI or CT) in-hospital and during follow-up (6 months, 12 months, 2 years). | Until hospital discharge, 6 months, 12 months and 2 years | 
| Stable angina | Angina as assessed by Seattle angina score (SAS) at follow-up (6 months, 12 months, 2 years). | 6 months, 12 months and 2 years | 
| Evidence for myocardial ischemia | Clinical or ECG-signs for myocardial ischemia during exercise ECG at 12-month follow-up. | 12 months | 
| Percent diameter stenosis | Percent diameter stenosis (%DS) at in in-segment (target lesion), in-device, proximal and distal (initial and in case of clinical-indicated re-angiography) (assessed by outcome-blinded Corelab analyses, Charite). | 24 months | 
| Minimal Lumen Diameter (MLD) | Minimal Lumen Diameter in-segment (target lesion), in-device, proximal and distal (initial and in case of clinical-indicated re-angiography) (assessed by outcome-blinded Corelab analyses, Charite). | 24 months | 
| TIMI-flow | TIMI-flow before (after mechanical recanalization) and after Magmaris Implantation (assessed by outcome-blinded Corelab analyses, Charite). | 24 month | 
| ACS-causing culprit lesion (OCT) | Mechanism of ACS (Plaque-Rupture vs. Plaque-Erosion vs. other mechanisms) and culprit-plaque-characteristics (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Max/Mean/minimal Mg-Stent diameter/area after implantation and lumen late loss (OCT) | Max/Mean/minimal Mg-Stent diameter/area after implantation and (in case of any clinical indicated re-angiography) lumen late loss as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Mean/minimal lumen diameter/area/volume | Mean/minimal lumen diameter/area/volume within the target lesion before and after Magmaris-Implantation, as well as (in case of any clinical indicated re-angiography) as difference Re-OCT to baseline-OCT (after Magmaris Implantation) (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Mean/minimal flow-area/volume | Mean/minimal flow-area/volume as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Intraluminal defect area/volume | Intraluminal defect area/volume at time point re-angiography/Re-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Modified vascular healing score | Modified vascular healing score (%HS; according to Räber EuroIntervention 2016; Sabate + Joner EHJ 2016) as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Presence of both malapposed and uncovered struts | Presence of both malapposed and uncovered struts (%MN) of the Mg-stent, which is an individual component of the endpoint Healing Score as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Presence of uncovered struts alone | Presence of both uncovered struts of the Mg-stent, which is an individual component of the endpoint Healing Score as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Presence of malapposed struts alone | Presence of both malapposed struts of the Mg-stent which is an individual component of the endpoint Healing Score as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Incomplete strut apposition (ISA) area/volume | Incomplete strut apposition (ISA) area/volume as difference Re-OCT to baseline-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Percentage of covered struts | Percentage of covered struts at Re-OCT follow-up (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Mean/maximal thickness of the struts coverage | Mean/maximal thickness of the struts coverage at Re-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Neointimal hyperplasia area/volume | Neointimal hyperplasia area/volume at Re-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Thickness of neointimal tissue developed over lipid rich plaque | Thickness of neointimal tissue developed over lipid rich plaque at Re-OCT follow-up (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner). | 24 months | 
| Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios) of MCG determination (MCG-substudy) | Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios) of MCG determination (ST-T Score (Angle dynamic), ST-T-analysis (distance parameter and rato-dynamics), PLP2 Score, VMCG Score (T-begin till Tmax and RP ½ till Tmax), T-dispersion Score) for the vessel with target lesion compared to angiography at ACS. A comparison to exercise-ECG at 12 months will also be performed. | 24 months | 
| Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios) of MCG Determination (MCG-substudy) | Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios)of MCG determination (ST-T Score (Angle dynamic), ST-T-analysis (distance parameter and rato-dynamics) PLP2 Score, VMCG Score (T-begin till Tmax and RP ½ till Tmax), T-dispersion Score) for characteristics of the ACS-causing culprit lesion compared to OCT before Magmaris-Implantation. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome, STE-ACS, NSTE-ACS, Magmaris