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

Not Applicable

Terminated

• Conditions: STEMI - ST Elevation Myocardial Infarction; Acute Coronary Syndrome; NSTEMI - Non-ST Segment Elevation MI
• Interventions: Device: Implantation of the Magmaris scaffold

• Registration Number: NCT03773081
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-08-21
• Study First Submitted: 2018-12-09
• Study First Submitted QC: 2018-12-09
• Study First Posted: 2018-12-12
• Status Verified: 2019-09
• Primary Completion: 2019-09-15
• Study Completion: 2019-09-15
• Last Update Submitted: 2019-09-15
• Last Update Posted: 2019-09-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Magmaris implantation	Implantation of the Magmaris scaffold	Subjects will undergo a PCI for the implantation of the Magmaris scaffold in accordance with the standard of care and standard hospital practice.

Primary Outcome Measures

Name	Time	Method
Procedural angiographical success	At the end of PCI	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 Outcome Measures

Name	Time	Method
ST-segment resolution at the electrocardiogram (ECG)	Within 60 minutes of primary PCI	ST-segment resolution at ECG.
Neointimal hyperplasia area/volume	24 months	Neointimal hyperplasia area/volume at Re-OCT (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner).
Major adverse cardiovascular events (MACE)	Until hospital discharge, 6 months, 12 months and 2 years	Cardiac death, any TV-MI, target vessel revascularization (TVR) in-hospital or during follow-up (6 months, 12 months, 2 years).
Cardiac death at all time points	Until hospital discharge, 6 months, 12 months and 2 years	Clinical Endpoint (in-hospital and at follow-up (6 months, 12 months, 2 years).
Any Bleeding	Until hospital discharge, 6 months, 12 months and 2 years	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).
Vascular cerebral events	Until hospital discharge, 6 months, 12 months and 2 years	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).
Target lesion revascularization	6 months, 12 months and 2 years	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.
Device-oriented composite endpoint (DOCE)	6 months, 12 months and 2 years	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.
All-cause death at all time points	Until hospital discharge, 6 months, 12 months and 2 years	Clinical Endpoint (in-hospital and at follow-up (6 months, 12 months, 2 years).
Percent diameter stenosis	24 months	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).
Presence of both malapposed and uncovered struts	24 months	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).
Evidence for myocardial ischemia	12 months	Clinical or ECG-signs for myocardial ischemia during exercise ECG at 12-month follow-up.
Procedural clinical success within hospital stay	Until hospital discharge, an expected average of 4 days	No in-hospital clinically-driven target lesion revascularization.
Magmaris Thrombosis	Until hospital discharge, 6 months, 12 months and 2 years	Any definite/probable per ARC defintion Magmaris thrombosis (in-hospital and during follow-up (6 months, 12 months, 2 years).
ACS-causing "culprit lesion" (OCT)	24 months	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).
Mean/minimal flow-area/volume	24 months	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).
Minimal Lumen Diameter (MLD)	24 months	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).
Max/Mean/minimal Mg-Stent diameter/area after implantation and lumen late loss (OCT)	24 months	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).
Mean/minimal lumen diameter/area/volume	24 months	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).
Modified vascular healing score	24 months	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).
Presence of malapposed struts alone	24 months	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).
Thickness of neointimal tissue developed over lipid rich plaque	24 months	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).
Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios) of MCG determination (MCG-substudy)	24 months	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.
Stable angina	6 months, 12 months and 2 years	Angina as assessed by Seattle angina score (SAS) at follow-up (6 months, 12 months, 2 years).
TIMI-flow	24 month	TIMI-flow before (after mechanical recanalization) and after Magmaris Implantation (assessed by outcome-blinded Corelab analyses, Charite).
Intraluminal defect area/volume	24 months	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).
Presence of uncovered struts alone	24 months	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).
Incomplete strut apposition (ISA) area/volume	24 months	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).
Percentage of covered struts	24 months	Percentage of covered struts at Re-OCT follow-up (assessed by outcome-blinded OCT Corelab analyses German Heart Center Munich: Prof. Dr. M. Joner).
Mean/maximal thickness of the struts coverage	24 months	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).
Diagnostic accuracy values (sensitivity, specificity, PPV, NPV, positive and likelihood ratios) of MCG Determination (MCG-substudy)	24 months	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.

Trial Locations

Locations (4)

Charité Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitätsklinikum Johannes Wesling; 🇩🇪 Minden, Germany

Herz- und Diabeteszentrum NRW; 🇩🇪 Bad Oeynhausen, Germany

Vivantes Klinikum im Friedrichshain; 🇩🇪 Berlin, Germany