Clinical trial NCT05908331: MagicTouch for Treatment of In-Stent Restenosis in Coronary Artery Lesions
Official title: MagicTouch Sirolimus-coated Balloon for Treatment of In-Stent Restenosis in Coronary Artery Lesions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: In-Stent Restenosis
Cardiovascular Diseases
Coronary Artery Disease
Keywords: Drug coated balloon
Sirolimus coated balloon
ISR
Magic Touch
SCB
Concept Medical
MAGICAL ISR
Lead sponsor: Concept Medical Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cardiovascular Research Foundation, New York
First posted: 2023-06-18
Enrollment: 492
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 randomized trial (MagicTouchTM vs. "plain old" balloon angioplasty \[POBA\])
Primary purpose: TREATMENT

Brief summary: 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: 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. All films, including unscheduled angiograms, are to be sent to the angiographic core laboratory for review. The angiographic core laboratory will be blinded.

Eligibility criteria: 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 (i.e. single and multiple stent layer ISR cases are eligible)
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. Prior DCB treatment (coronary or off-label peripheral) of target lesion ISR
5. Cardiogenic shock (defined as persistent hypotension \[systolic blood pressure \<90 mm Hg\] or requiring vasoactive or hemodynamic support, including IABP)
6. Subject is intubated
7. Known left ventricular ejection fraction \<30%
8. Relative or absolute contraindication to DAPT for at least 1 month (e.g., planned surgeries that cannot be delayed)
9. Subject has an indication for chronic oral anticoagulation treatment and a contraindication for concomitant treatment with a P2Y12 inhibitor
10. If femoral access is planned, significant peripheral arterial disease which precludes safe insertion of a 6F sheath
11. Hemoglobin \<9 g/dL
12. Platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3
13. White blood cell count \<3,000 cells/mm3
14. Active infection undergoing treatment
15. Clinically significant liver disease
16. Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) to be \<30ml/min by the MDRD formula
17. Active peptic ulcer or active bleeding from any site
18. Bleeding from any site requiring active medical attention within the prior 8 weeks
19. History of bleeding diathesis or coagulopathy or likely to refuse blood transfusions
20. Cerebrovascular accident (CVA) within 3 months or has any permanent neurological defect as a result of CVA
21. 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
22. 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)
23. Patient is participating in or plans to participate in any other investigational drug or device trial that has not reached its primary endpoint
24. Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before index procedure)
25. Women who intend to become pregnant within 12 months after the index procedure
26. Patient has received an organ transplant or is on a waiting list for an organ transplant
27. Patient has received chemotherapy within 30 days before the index procedure or scheduled to receive chemotherapy any time after the index procedure
28. 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 40mm length DCB (see Angiographic Inclusions #5 and #6 above)
2. ISR lesion in the target vessel in a segment that corresponds to a previously established/documented bare metal stent (BMS)
3. Unprotected left main lesions \>50% or left main intervention
4. Primary PCI for STEMI
5. Coronary artery disease judged more suitable for surgical revascularization per guidelines and local heart team discussion
6. 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
7. Prior brachytherapy or DCB treatment of target lesion
8. Target lesion is a bifurcation restenosis involving both branches of a bifurcation in which the side branch reference vessel diameter is \>2.0 mm
9. Target lesions located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft
10. Target lesion contains large thrombus
11. Target lesion is heavily calcified
12. Target lesion is a chronic total occlusion (or subtotal) without adequate lesion preparation.\* Total and subtotal occlusions may be enrolled assuming they can be crossed with a wire and demonstrate TIMI grade 3 flow at the time of randomization.
13. Diffuse distal disease to target lesion with impaired runoff

Primary outcomes:
measure: TLF (Target Lesion Failure)
timeFrame: 12 months
Secondary outcomes:
measure: MACE (Major adverse cardiovascular events)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: TVF (Target vessel failure)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Any revascularization
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: ID-TLR (Ischemia-Driven Target Lesion Revascularization)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: TLR (Target Lesion Revascularization)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: ID-TVR (Ischemia-Driven Target Vessel Revascularization)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: TVR (Target Vessel Revascularization)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: All-cause mortality
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Cardiovascular mortality
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Any MI (Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: TV-MI (Target Vessel Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Q-wave MI (Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Non-Q-wave MI (Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Cardiovascular mortality or MI (Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: All-cause mortality or MI (Myocardial Infarction)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: All-cause mortality, MI (Myocardial Infarction), or TVR (Target Vessel Revascularization)
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Any definite or probable target lesion stent thrombosis by ARC (Academic Research Consortium) criteria
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Probable target lesion stent thrombosis by ARC (Academic Research Consortium) criteria
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Definite target lesion stent thrombosis by ARC (Academic Research Consortium) criteria
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: BARC (Bleeding Academic Research Consortium) type 3-5 bleeding
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
measure: Procedure Success
timeFrame: 30 days and 6, 12, 24, 36, 48, and 60 months
Other outcomes:
measure: Angina as assessed by SAQ-7 (Seattle Angina Questionnaire)
timeFrame: 30 days, 6, 12, 24, 36, 48 and 60 months
Locations:
city: Birmingham
country: United States
facility: Cardiology, PC - Princeton Baptist Medical Center
state: Alabama
city: Gilbert
country: United States
facility: Dignity Health - Mercy Gilbert Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars - Sinai Medical Center
state: California
city: New Haven
country: United States
facility: Yale University / Yale New Haven Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Cheek-Powell Heart and Vascular Pavilion
state: Florida
city: Clearwater
country: United States
facility: Clearwater Cardiovascular and Interventional Consultants
state: Florida
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute Research Foundation
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital / University of South Florida
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Coon Rapids
country: United States
facility: Metropolitan Heart and Vascular Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Tupelo
country: United States
facility: Cardiology Associates Research, LLC
state: Mississippi
city: Tupelo
country: United States
facility: Cardiology Associates Research, LLC
state: Mississippi
city: Pomona
country: United States
facility: AtlantiCare Regional Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Division
state: New York
city: New York City
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: VA New York Harbor Healthcare System
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/NYPH
state: New York
city: Raleigh
country: United States
facility: NC Heart and Vascular Research, LLC
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health (OU Health)
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott and White Heart and Vascular Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White - The Heart Hospital - Plano
state: Texas
city: Morgantown
country: United States
facility: West Virginia University and Vascular Institute
state: West Virginia
Study officials:
References: