First-In-Human Trial of the MiStent Drug-Eluting Stent (DES) in Coronary Artery Disease

Study Overview
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Brief Summary
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The DESSOLVE I clinical trial is to assess the safety and performance of the sirolimus-eluting MiStent SES.

Detailed Description
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The DESSOLVE I clinical trial is to assess the safety and performance of the sirolimus-eluting MiStent for the treatment for improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to discrete de novo lesions < 20 mm in length in the native coronary arteries with reference vessel diameters between 2.5 mm and 3.5 mm.

Official Title
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A First-In-Human Trial of a New Novel DES (MiStent System) With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesions in the Native Coronary Arteries

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: MiStent SES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female patients 18-85 years; Stable or unstable angina pectoris, ischemia, or silent ischemia; Planned single, de novo, types A, B1 and B2 coronary lesions; Target lesion located in a native coronary artery; Target lesion vessel diameter 2.5 to 3.5 mm amenable to treatment with a maximum 23 mm long stent; Target lesion >50% diameter stenosis; Patients eligible for percutaneous coronary intervention (PCI); Acceptable candidate for myocardial revascularization surgery; A patient may have one additional critical non-target lesion. The patient will provide written informed consent. Exclusion Criteria: Female of childbearing potential not on some form of birth control with a confirmed negative pregnancy test at baseline; Recent Q-wave myocardial infarction occurred <72 hours prior to the index procedure. Recent myocardial infarction with elevated levels of cardiac markers; Left ventricular ejection fraction <30%; Patients in cardiogenic shock; Cerebrovascular accident or transient ischemic attack within 6 months; Active GI bleed within three months; Any prior true anaphylactic reaction to contrast agents; Patient receiving/scheduled to receive chemotherapy within 30-days before or after the index procedure; Patient is receiving immunosuppressive therapy or has known life-limiting immunosuppressive/autoimmune disease; Renal dysfunction (creatinine > 2.0 mg/dL or 177 µmol/L); Platelet count <100,000 cells/mm³ or >700,000 cells/mm³; White blood cell count <3,000 cells/mm3; Hepatic disease; Heart transplant recipient; Known contraindication to dual antiplatelet therapy; Known hypersensitivity to sirolimus, cobalt-chromium, or to medications such as aspirin, heparin, and all three of the following: clopidogrel bisulfate (Plavix), ticlopidine (Ticlid), and Prasugrel (Effient); Life expectancy <12 months; Any major medical condition that may interfere with the optimal participation of the patient in this study; Patient is currently participating/planning to participate in an investigational drug or another device study prior to completing 12-months follow-up; Target vessel(s) has been treated within 10 mm proximal or distal to target lesion with any type of PCI within a year prior to index procedure; Planned or actual target vessel(s) treatment with an unapproved device, directional or rotational coronary atherectomy, laser, cutting balloon, or transluminal extraction catheter prior to stent placement; Previous coronary intravascular brachytherapy; Planned coronary angioplasty or coronary artery bypass grafting (CABG)in the first 9 months after the index procedure; Prior PCI of a non-target vessel must be at least 30 days prior to study enrollment; The intent to direct stent the target lesion; Angiographic Exclusion Criteria: Assessed prior to stent placement; In-stent restenotic target lesion; More than one lesion requiring treatment in the target vessel; Target vessel diameter <2.5 mm or >3.5 mm; Target lesion not amenable to treatment with a 23 mm long stent; Unprotected coronary artery branch lesion (≥50% DS); Target lesion located in a surgical bypass graft; Total vessel occlusion; Target lesion with ostial location; Target lesion located in a lateral branch bifurcation >2.5mm or requiring lateral branch stenting; Calcified target lesion that anticipates unsuccessful/impracticable predilation; Target vessel excessive tortuosity or proximal angulation (>90 degrees); Thrombus present in target vessel; More than one non-target critical lesion; Non-target lesion to be treated during the index procedure meets any of the following criteria: Within the target vessel; Within a bypass graft; Left main location; Chronic total occlusion; Involves a complex bifurcation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| Experimental: MiStent SES<br>The MiStent SES is a device/drug combination comprised of two components; a stent and a drug product (sirolimus within an absorbable polymer coating). | Device: MiStent SES<br>* The MiStent SES is a device/drug combination comprised of two components; a stent and a drug product (sirolimus within an absorbable polymer coating).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiographic In-Stent Late Lumen Loss | In-stent late lumen loss as measured by the angiographic core laboratory as the difference between the post-procedure minimal lumen diameters (MLD) in the treated segment (stented region) minus the MLD in the same region at follow-up. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Major Adverse Cardiac Events (MACE) | Major Adverse Cardiac Events (MACE) defined as death, myocardial infarction (Q-wave and non-Q-wave) and target vessel revascularization (TVR) | 240 days | 
| Device Success | Achievement of a final in-stent residual diameter stenosis of <50% (by QCA), using the assigned device only | 8 hours | 
| Lesion Success | Achievement of a final in-stent residual diameter stenosis of <50% (by QCA) using any percutaneous method | 8 hours | 
| Procedural Success | Achievement of a final in-stent residual diameter stenosis of <50% (by QCA) using the assigned device (including any adjunctive devices) without cardiac death, Myocardial infarction (MI) or repeat revascularization of the target lesion pre-hospital discharge | 8 hours | 
| Total Mortality | Total mortality (cardiac and non-cardiac) | 240 days | 
| Total Myocardial Infarction (MI) | Q-wave MI (QWMI): requires one of the following criteria: the development of new abnormal Q waves in ≥2 contiguous ECG leads not present on the patient's baseline (i.e., before intervention) in association with a >2x upper limit normal elevation of creatine kinase (CK) levels. In the absence of ECG data, the clinical events committee may adjudicate a Q-wave MI based on the clinical scenario and appropriate cardiac enzyme data; chest pain or other acute symptoms consistent with myocardial ischemia and new pathological Q waves in ≥2 contiguous ECG leads in the absence of timely cardiac enzyme data. Non-Q-wave MI (NQWMI): the elevation of CK levels (≥2 times ULN) with elevated CK-MB enzyme levels in the absence of new pathologic Q waves. | 240 days | 
| Clinically-driven Target Lesion Revascularization (TLR) Rates | A revascularization is considered clinically driven if angiography at follow-up shows a percent diameter stenosis ≥ 50% (Angiographic Core Laboratory QCA assessment) and if one of the following occurs: A positive history of recurrent angina pectoris, presumably related to the target vessel; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve); A target lesion revascularization (TLR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms. | 240 days | 
| Clinically-driven Target Vessel Revascularization (TVR) Rates | A revascularization is considered clinically driven if angiography at follow-up shows a percent diameter stenosis ≥ 50% (Angiographic Core Laboratory QCA assessment) and if one of the following occurs: A positive history of recurrent angina pectoris, presumably related to the target vessel; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve); A target vessel revascularization (TVR) with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or symptoms. | 240 days | 
| Target Vessel Failure (TVF) | Target vessel failure (TVF) is defined as the composite endpoint of: cardiac death, target-vessel myocardial infarction (Q wave or non-Q wave), and clinically indicated target vessel revascularization | 240 days | 
| Target Lesion Failure (TLF) | Target lesion failure (TLF) is defined as the composite endpoint of: cardiac death, target-lesion myocardial infarction (Q wave or non-Q wave), and clinically indicated target lesion revascularization | 240 days | 
| Stent Thrombosis | The presence of an intracoronary thrombus that originates in the stent or in the segments 5 mm proximal or distal to the stent post-procedure | 240 days | 
| Angiographic Evaluation: In-stent Binary Restenosis | Binary Restenosis is defined as ≥50% luminal narrowing at follow-up angiography. | 4 months, 6 months, 8 months | 
| Angiographic Evaluation: In-stent Binary Restenosis | Binary Restenosis is defined as ≥50% luminal narrowing at follow-up angiography. | 18 months | 
| Intravascular Ultrasound (IVUS) Evaluation: % Neointimal Volume Obstruction | % neointimal volume obstruction is defined as the neointimal volume divided by stent volume. | 8 months | 
| IVUS Evaluation: % Neointimal Volume Obstruction | % neointimal volume obstruction is defined as the neointimal volume divided by stent volume. | 18 months | 
| Optical Coherence Tomography (OCT) Evaluation: % Stent Strut Uncovered | % stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections. | 8 months | 
| OCT Evaluation: % Stent Strut Uncovered | % stent strut uncovered is defined as the ratio of uncovered struts to total struts in all cross-sections. | 18 M | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Disease, Drug-eluting Stent, Sirolimus