Overview

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).

Eligibility

Inclusion Criteria:

1. Subject is at least 18 years old
2. Subject (or legal guardian) understands the trial requirements and treatment procedures and provides written informed consent prior to any trial-specific tests or treatment
3. Patient with an indication for PCI due to suspected in-stent restenosis
4. 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:

1. In-stent restenosis after drug-eluting stent implantation(s) in the target lesion
2. 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
3. Successful lesion preparation (residual stenosis <30%), without complications (no or slow flow, flow-limiting dissection, perforation, distal embolization) and without plan for stenting
4. Target lesion in a native coronary artery
5. Thrombolysis In Myocardial Infartction (TIMI) grade flow ≥1 in target lesion
6. Target reference vessel diameter (visual estimation) >2.0 and ≤4.0 mm
7. Target lesion length (including tandem lesions) ≤36.0 mm (visual estimation) and can be covered by only one balloon
8. 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)
9. 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):

1. STEMI within 72 hours of presentation to the first treating hospital, whether a transfer facility or the study hospital
2. NSTEACS in whom the biomarkers have not peaked
3. PCI within the 24 hours prior to the index procedure (not including PCI performed in non-target lesions during the index procedure)
4. Cardiogenic shock (defined as persistent hypotension [systolic blood pressure <90 mm Hg] or requiring vasoactive or hemodynamic support, including IABP)
5. Subject is intubated
6. Known left ventricular ejection fraction <30%
7. Relative or absolute contraindication to DAPT for at least 1 month (e.g., planned surgeries that cannot be delayed)
8. Subject has an indication for chronic oral anticoagulation treatment and a contraindication for concomitant treatment with a P2Y12 inhibitor
9. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath
10. Hemoglobin <9 g/dL
11. Platelet count <100,000 cells/mm3 or >700,000 cells/mm3
12. White blood cell count <3,000 cells/mm3
13. Active infection undergoing treatment
14. Clinically significant liver disease
15. Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) to be <30ml/min by the MDRD formula
16. Active peptic ulcer or active bleeding from any site
17. Bleeding from any site requiring active medical attention within the prior 8 weeks
18. History of bleeding diathesis or coagulopathy or likely to refuse blood transfusions
19. Cerebrovascular accident (CVA) within 3 months or has any permanent neurological defect as a result of CVA
20. 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

21. 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)

22. Patient is participating in or plans to participate in any other investigational drug or device trial that has not reached its primary endpoint
23. Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before index procedure)
24. Women who intend to become pregnant within 12 months after the index procedure
25. Patient has received an organ transplant or is on a waiting list for an organ transplant
26. Patient has received chemotherapy within 30 days before the index procedure or scheduled to receive chemotherapy any time after the index procedure
27. 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):
          1. 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)
          2. Unprotected left main lesions >50% or left main intervention
          3. Primary PCI for STEMI
          4. Coronary artery disease judged more suitable for surgical revascularization per
             guidelines and local heart team discussion
          5. 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
          6. Prior brachytherapy or DCB treatment of target lesion
          7. Target lesion is a bifurcation restenosis involving both branches of a bifurcation in
             which the side branch reference vessel diameter is >2.0 mm
          8. Target lesions located within an arterial or saphenous vein graft or distal to a
             diseased arterial or saphenous vein graft
          9. Target lesion contains large thrombus
         10. Target lesion is heavily calcified
         11. Target lesion is a chronic total occlusion
         12. Diffuse distal disease to target lesion with impaired runoff