Safety and Efficacy of Everolimus - Eluting Bioresorbable Vascular Scaffold for Cardiac Allograft Vasculopathy

Study Overview
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Brief Summary
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The CART Pilot study was designed to provide preliminary observations (about performance and safety) and generate hypotheses for future studies . The primary goal of the study is to evaluate the performance at one year of second-generation ABSORB Bioresorbable Vascular Scaffold (BVS)(Abbott Vascular, Santa Clara, CA , USA), the Everolimus Eluting Bioresorbable Vascular Scaffold, in heart transplant recipients affected by cardiac allograft vasculopathy (CAV) and significative coronary stenosis. The secondary objectives are: to collect data about the procedural and clinical outcomes post-procedure , 30 days, 180 days and at 1,2 and 3-year follow-up, of patients who underwent ABSORB BVS implantation in order to investigate the safety of the device in CAV population; to evaluate the progression of the disease and the its interactions with the study device by using data derived from multi-imaging invasive techniques. The vascular reparative therapy and in particular the BVS technology showing important advantages in terms of endothelial preservation, adequate vasomotion, and restoration of the media and adventitia of the vessel wall, could represent a new and more effective therapeutic option, compared to bare-metal and drug-eluting stent technologies, for transplanted patients, since all these mechanisms may, at least in part, counteract the detrimental changes leading to CAV, namely constrictive remodeling and rapid atherosclerosis progression. Subjects enrolled into the clinical study will be male or female derived from the heart transplant recipients population of every participating center. The clinical study will enroll 30 subjects. Subjects, who underwent the yearly expected coronary angiography follow-up after heart transplant surgery, meeting the general and angiographic inclusion and exclusion criteria (eligibility will be assessed by Heart Team consensus) will be asked to sign an informed consent form. Subjects who do not meet inclusion and exclusion criteria are subject to the standard follow-up of heart transplant (HTx) recipients and will undergo to an invasive evaluation after 365 ± 28 days. The study comprises two distinct phases: the enrollment phase which starts with the recruitment of the first subject and it is planned to last one year; the follow-up phase which is planned to last three years from the enrollment of the last patient. The total duration of the study will be of four years, including both the enrollment and the follow-up phases

Official Title
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Everolimus-eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: A Prospective Multicenter Pilot Study

Conditions
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Cardiac Allograft Vasculopathy

Intervention / Treatment
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* Device: Everolimus-Eluting Bioresorbable Vascular Scaffold (ABSORB)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion criteria: All the enrolled patients must be heart transplanted recipients. The inclusion criteria must follow the most recent instructions for use (IFU) for BVS which may include but are not Limited to the following: Patient must be at least 18 years of age at the time of signing the Informed Consent Form Patient must be eligible for percutaneous coronary intervention (PCI) Patient is to be treated for de novo lesions located in previously untreated vessels. Patient must agree to undergo all required follow-up visits and data collection. Angiographic inclusion criteria: • Presence of at least one critical angiographic de novo lesion (DS ≥70%) or a non-critical angiographic de novo lesion (50% ≤ DS <70%) associated with concomitant signs or symptoms of myocardial ischemia. Any intermediate lesion without a clear evidence of ischemia will be interrogated by means of fractional flow reserve assessment with a pressure wire, as recommended by current international guidelines Exclusion Criteria: General Exclusion criteria: Inability to obtain a signed informed consent from potential patient. Contraindications for drug eluting scaffold implantation (known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, clopidogrel, ticlopidine, prasugrel, and ticagrelor, everolimus, poly (L-lactide), poly (D,L-lactide), or platinum, or with contrast sensitivity, who cannot be adequately premedicated). Female patients with childbearing potential with a positive pregnancy test within 7 days prior to the index procedure. Prior Coronary Artery Bypass Graft (CABG) at any time or planned CABG.

Ages Eligible for Study
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Minimum Age: 18 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: ABSORB Bioresorbable Vascular Scaffold<br>Everolimus-Eluting Bioresorbable Vascular Scaffold implantation | Device: Everolimus-Eluting Bioresorbable Vascular Scaffold (ABSORB)<br>* Placement of bioresorbable vascular scaffold in presence of at least one critical angiographic de novo lesion (DS ≥70%) or a non-critical angiographic de novo lesion (50% ≤ DS <70%) associated with concomitant signs or symptoms of myocardial ischemia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Restenosis rate (bioresorbable vascular scaffold), defined as >50% narrowing at the stent site or 5 mm proximal or distal to the stent, as assessed by Quantitative Coronary Analysis. |  | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success (lesion based analysis) |  | Basal procedure | 
| Procedural success (subject based analysis) |  | Basal procedure | 
| Death (cardiac, vascular, non-cardiovascular) |  | 30 days, 180 days, 2 years and 3 years | 
| Myocardial infarction (MI: Q wave Myocardial Infarction (QMI) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Target lesion revascularization (TLR) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Target vessel revascularization (TVR) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Non-target vessel revascularization (NTVR) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Composite (Death/All MI/ Graft failure) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Composite (Cardiac death/TV-MI/TLR ) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Composite (Cardiac death/all MI/TLR ) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Composite (Cardiac death/all MI/TVR) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Composite (Death/All MI/all revascularization) |  | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Timing (Acute) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Timing (Subacute) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Timing (Late) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Timing (Very late) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Evidence (Definite) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Evidence (Probable) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Scaffold thrombosis | Evidence (Possible) | 30 days, 180 days, 1 year, 2 years and 3 years | 
| Angiographic Endpoints | In-scaffold Reference Vessel Diameter (RVD) (mm) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-scaffold Minimal Lumen Diameter (MLD) (mm) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-scaffold Diameter Stenosis (DS) (%) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-scaffold late loss (mm) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | Proximal late loss (mm) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | Distal late loss (mm) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-scaffold absolute minimal luminal area (mm2) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-scaffold minimal luminal cross sectional area (mm2) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-segment late loss (mm) In-stent binary restenosis (%) | Basal procedure, 1 year and 3 years | 
| Angiographic Endpoints | In-segment binary restenosis | Basal procedure, 1 year and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Vessel (EEM) area (mm2) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Vessel volume (mm3) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Average lumen area (mm2) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Lumen volume (mm3) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Plaque area (mm2) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Plaque volume (mm3) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Minimal lumen area (mm2) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Lumen area stenosis (%) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Vessel volume index (mm3/mm) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Lumen volume index (mm3/mm) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Plaque volume index (mm3/mm) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Plaque burden, % | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Projected MLD (mm) | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Dense calcium volume, area, percentage | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Necrotic core volume, area, percentage | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Fibrofatty volume, area, percentage | Basal procedure and 3 years | 
| Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints | Fibrous volume, area, percentage | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Maximal intimal thickness (MIT) (mm) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Media thickness at MIT (mm) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Mean lumen area (mm2) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Intimal area (mm2) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Maximal, minimal and mean lumen diameter (mm) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Discernible struts | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Atherosclerosis assessment (Eccentric plaque) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Atherosclerosis assessment (Calcification) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Atherosclerosis assessment (Lipid) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Vulnerable plaque assessment (thin-cap fibroatheroma) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Vulnerable plaque assessment (macrophages) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Vulnerable plaque assessment (microchannels) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Vulnerable plaque assessment (calcific nod) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Lesions assessment (Intimal laceration) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Lesions assessment (plaque rupture) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Lesions assessment (intraluminal thrombus) | Basal procedure and 3 years | 
| Optical Coherence Tomography Endpoints | Lesions assessment (layered complex plaque) | Basal procedure and 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Allograft Vasculopathy, Heart Transplant, Bioresorbable Vascular Scaffold