MagicTouch for Treatment of In-Stent Restenosis in Coronary Artery Lesions

Study Overview
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Brief Summary
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A Prospective, Multicenter, Randomized, Two-Arm, Single-blind Superiority Trial to Evaluate the Safety and Efficacy of the MagicTouch™ Sirolimus- Coated Balloon in the Treatment of Coronary Drug-Eluting Stent In-Stent Restenosis. Subjects with prior DES implantation presenting with ISR lesions undergoing PCI will be randomized into two groups: treatment with the MagicTouch™ sirolimus-coated balloon or POBA on a 2:1 basis. Approximately 492 subjects will be enrolled in the randomized study in a maximum of 50 study sites located in the United States. The goal is to establish the safety and efficacy of the MagicTouch™ sirolimus- coated balloon in treatment of coronary in-stent restenosis (ISR).

Detailed Description
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All subjects providing informed consent will have their medical history reviewed and will undergo a physical examination, laboratory screen, and a standardized 12-lead ECG within 7 days of procedure. Women of childbearing potential will have a pregnancy test within one week prior to the procedure. If subjects meet the inclusion and exclusion criteria of the study, they will be randomized to one of two treatment groups, and will then undergo treatment with MagicTouch™ sirolimus-coated balloon or POBA of the target ISR lesion, per trial protocol. One pre-procedure and all post-procedure biomarker blood draws will be sent to a central core laboratory for analysis of troponin T. Evaluation of post-procedural biomarker blood draws in local laboratories are not mandated but may be performed as part of standard of care. During the index hospitalization, patients will undergo a clinical assessment and 12-lead ECG; and they will have cardiac biomarkers drawn before the intervention to establish baseline biomarker level and confirmation that the biomarkers are falling. At least one post procedure biomarker (core lab) will be drawn at a minimum of 4 hours after PCI as part of the assessment of periprocedural myocardial infarction and significant periprocedural myocardial injury (at 6-8 hour intervals depending on whether the patient remains admitted). If no procedural complications have occurred and there are no signs of ischemia on post-procedure ECG or clinical assessment, the patient may be discharged per local practice and no additional biomarker levels need to be drawn (beyond the protocol-mandated core laboratory draw at a minimum of 4 hours). If the patient remains admitted cardiac biomarkers (core lab) should be drawn every 6-8 hours until at least 2 total post-procedural core laboratory biomarker draws have passed or clinical standard-based biomarker levels have peaked per local labs or the patient is discharged. After hospital discharge, subjects will be followed at 30 days (+1 week), 6 months (+2 weeks), and 12 months (+1 month) and then 24, 36, 48 and 60 months (+1 month) post procedure. Yearly vital status information will be collected by telephone follow-up. At the 12-month visit, subjects will undergo 12-lead ECG, blood count, coagulation profile and blood chemistry tests. New and ongoing AEs and concomitant medications will also be assessed. All elective angiograms performed on the target vessel during the 12-month follow-up period should be preceded by a physician evaluation, during which the physician will indicate whether the subject's clinical status warrants revascularization, i.e. the subject has clinical evidence of ischemia.

Official Title
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MagicTouch Sirolimus-coated Balloon for Treatment of In-Stent Restenosis in Coronary Artery Lesions

Conditions
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In-Stent Restenosis, Cardiovascular Diseases, Coronary Artery Disease

Intervention / Treatment
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* Device: Sirolimus Drug Coated Balloon
* Device: Plan balloon Angioplasty (POBA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years old Subject (or legal guardian) understands the trial requirements and treatment procedures and provides written informed consent prior to any trial-specific tests or treatment Patient with an indication for PCI due to suspected in-stent restenosis Non-target lesion PCI are allowed in non-target vessels to be treated with approved interventional devices prior to randomization as follows: Angiographic Inclusion Criteria: In-stent restenosis after drug-eluting stent implantation(s) in the target lesion Target lesion must have visually estimated stenosis ≥50% and less than 100% diameter stenosis in symptomatic patients; or a visually estimated target lesion diameter stenosis of ≥70%, or by evidence of ischemia by coronary physiology (fractional flow reserve [FFR] ≤0.80 or non-hyperemic pressure ratio [NHPR] ≤0.89) in absence of symptoms Successful lesion preparation (residual stenosis <30%), without complications (no or slow flow, flow-limiting dissection, perforation, distal embolization) and without plan for stenting Target lesion in a native coronary artery Thrombolysis In Myocardial Infartction (TIMI) grade flow ≥1 in target lesion Target reference vessel diameter (visual estimation) >2.0 and ≤4.0 mm Target lesion length (including tandem lesions) ≤36.0 mm (visual estimation) and can be covered by only one balloon One ISR target lesion (overlapping stents are allowed) to be treated per patient and in single major coronary artery or side branch (reference vessel diameter >2.0 mm) Other coronary lesions (ISR or non-ISR) in non-target vessel are allowed and may be treated by any approved interventional device, but must be treated successfully prior to randomization Exclusion Criteria: General Exclusion Criteria (all must be absent for the patient to be eligible): STEMI within 72 hours of presentation to the first treating hospital, whether a transfer facility or the study hospital NSTEACS in whom the biomarkers have not peaked PCI within the 24 hours prior to the index procedure (not including PCI performed in non-target lesions during the index procedure) Cardiogenic shock (defined as persistent hypotension [systolic blood pressure <90 mm Hg] or requiring vasoactive or hemodynamic support, including IABP) Subject is intubated Known left ventricular ejection fraction <30% Relative or absolute contraindication to DAPT for at least 1 month (e.g., planned surgeries that cannot be delayed) Subject has an indication for chronic oral anticoagulation treatment and a contraindication for concomitant treatment with a P2Y12 inhibitor If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath Hemoglobin <9 g/dL Platelet count <100,000 cells/mm3 or >700,000 cells/mm3 White blood cell count <3,000 cells/mm3 Active infection undergoing treatment Clinically significant liver disease Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) to be <30ml/min by the MDRD formula Active peptic ulcer or active bleeding from any site Bleeding from any site requiring active medical attention within the prior 8 weeks History of bleeding diathesis or coagulopathy or likely to refuse blood transfusions Cerebrovascular accident (CVA) within 3 months or has any permanent neurological defect as a result of CVA Known allergy to the study device components or protocol-required concomitant medications: - sirolimus (as well as other limus drugs, analogues, or similar compounds), aspirin, clopidogrel and prasugrel and ticagrelor, heparin and bivalirudin, or iodinated contrast that cannot be adequately pre-medicated Any co-morbid condition that may cause non-compliance with the protocol (e.g. dementia, substance abuse, etc.) or reduce life expectancy to <24 months (e.g. cancer, heart failure, lung disease, severe valvular disease) Patient is participating in or plans to participate in any other investigational drug or device trial that has not reached its primary endpoint Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before index procedure) Women who intend to become pregnant within 12 months after the index procedure Patient has received an organ transplant or is on a waiting list for an organ transplant Patient has received chemotherapy within 30 days before the index procedure or scheduled to receive chemotherapy any time after the index procedure Patient is receiving oral or intravenous immunosuppressive therapy or has known life-limiting immunosuppressive or autoimmune disease. Inhaled steroid and steroid use for contrast- allergy prophylaxis or treatment are allowed Angiographic Exclusion Criteria (visual estimate) (all must be absent for the patient to be eligible): More than 1 ISR lesion in the target vessel in segments that cannot be treated by a single 40 mm length DCB (see Angiographic Inclusions #5 and #6 above) Unprotected left main lesions >50% or left main intervention Primary PCI for STEMI Coronary artery disease judged more suitable for surgical revascularization per guidelines and local heart team discussion Another lesion in either the target vessel or non-target vessel is present that requires or has a high probability of requiring PCI within 12 months after the index procedure Prior brachytherapy or DCB treatment of target lesion Target lesion is a bifurcation restenosis involving both branches of a bifurcation in which the side branch reference vessel diameter is >2.0 mm Target lesions located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft Target lesion contains large thrombus Target lesion is heavily calcified Target lesion is a chronic total occlusion Diffuse distal disease to target lesion with impaired runoff

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 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: 2:1 randomized trial (MagicTouchTM vs. plain old balloon angioplasty [POBA])
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MagicTouch Sirolimus-Coated Balloon<br>Magic TouchTM is a Sirolimus Coated Balloon catheter intended to be used in coronary applications, treats the atherosclerosis of the coronary arteries by eluting the immunosuppressant agent Sirolimus without leaving behind a metallic scaffold. | Device: Sirolimus Drug Coated Balloon<br>* Magic TouchTM (Concept Medical) is a semi-compliant sirolimus drug coated balloon (SCB) for PCI, based on a polymer-free and nanocarrier based drug delivery technology.<br>|
| Active Comparator: POBA<br>plain old balloon angioplasty | Device: Plan balloon Angioplasty (POBA)<br>* Plan balloon used to open clogged or narrow coronary arteries due to underlying atherosclerosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TLF (Target Lesion Failure) | The composite rate of cardiac death, target-vessel MI (Myocardial Infarction) or ischemia-driven TLR (Target Lesion Revascularization) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE (Major adverse cardiovascular events) | composite of cardiovascular mortality, any MI (Myocardial Infarction), and ID-TLR (Ischemia-Driven Target Lesion Revascularization) | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| TVF (Target vessel failure) | composite of cardiovascular mortality, ID-TVR (Ischemia-Driven Target Vessel Revascularization), and TV-MI (Target Vessel Myocardial Infarction) | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Any revascularization | any repeat PCI or CABG | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| ID-TLR (Ischemia-Driven Target Lesion Revascularization) | Repeat revascularization of the target lesion due to recurrent ischemia | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| TLR (Target Lesion Revascularization) | Repeat revascularization of the target lesion | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| ID-TVR (Ischemia-Driven Target Vessel Revascularization) | Repeat revascularization of the target vessel due to recurrent ischemia | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| TVR (Target Vessel Revascularization) | Repeat revascularization of the target vessel | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| All-cause mortality | Death from any cause | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Cardiovascular mortality | Death due to coronary artery disease or complications of coronary treatment | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Any MI (Myocardial Infarction) | Any Myocardial Infarction | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| TV-MI (Target Vessel Myocardial Infarction) | Myocardial Infarction related to the target vessel | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Q-wave MI (Myocardial Infarction) | Myocardial Infarction demonstrated by new pathological Q waves on ECG | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Non-Q-wave MI (Myocardial Infarction) | Myocardial Infarction not demonstrated by new pathological Q waves on ECG | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Cardiovascular mortality or MI (Myocardial Infarction) | Either cardiovascular death or any Myocardial Infarction | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| All-cause mortality or MI (Myocardial Infarction) | Either death from any cause or any Myocardial Infarction | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| All-cause mortality, MI (Myocardial Infarction), or TVR (Target Vessel Revascularization) | Death from any cause, any Myocardial Infarction, or Target Vessel Revascularization | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Any definite or probable target lesion stent thrombosis by ARC (Academic Research Consortium) criteria | Definite or probable stent thrombosis in the target lesion according to the ARC (Academic Research Consortium) definition | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Probable target lesion stent thrombosis by ARC (Academic Research Consortium) criteria | Probable stent thrombosis in the target lesion according to the ARC definition | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Definite target lesion stent thrombosis by ARC (Academic Research Consortium) criteria | Definite stent thrombosis in the target lesion according to the ARC definition | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| BARC (Bleeding Academic Research Consortium) type 3-5 bleeding | Significant or severe bleeding according to the BARC definition | 30 days and 6, 12, 24, 36, 48, and 60 months | 
| Procedure Success | ability to deliver the device and achieve a less than 30% residual stenosis by QCA (quantitative coronary angiography) without major complication or bailout stenting | 30 days and 6, 12, 24, 36, 48, and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magic Touch, SCB, Concept Medical, ISR, Drug coated balloon, Sirolimus coated balloon