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

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

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

Study Overview

• Status: Completed
• Conditions: Cardiac Allograft Vasculopathy
• Intervention / Treatment: Device: Everolimus-Eluting Bioresorbable Vascular Scaffold (ABSORB)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Cagliari, Italy
    • Azienda Ospedaliera Brotzu
  • Naples, Italy
    • Azienda Ospedaliera Specialistica dei Colli
  • Padua, Italy
    • Azienda Ospedaliera di Padova
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Rome, Italy
    • Azienda Ospedaliera San Camillo Forlanini
  • Rome, Italy
    • European Hospital
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria Integrata Di Udine (Asuiud)
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria integrata Verona
• Netherlands
  • Rotterdam, Netherlands
    • Cardialysis Core Laboratory For Imaging
  • Rotterdam, Netherlands
    • Thoraxcenter, Universtity of Rotterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ABSORB Bioresorbable Vascular Scaffold; Everolimus-Eluting Bioresorbable Vascular Scaffold implantation	Device: Everolimus-Eluting Bioresorbable Vascular Scaffold (ABSORB); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Principal Investigator: Flavio L Ribichini, MD, Universita di Verona; Principal Investigator: Michele Pighi, MD, Universita di Verona

Publications and helpful links

General Publications

• Ribichini F, Pighi M, Faggian G, Vassanelli C. Bioresorbable vascular scaffolds in cardiac allograft vasculopathy: a new therapeutic option. Am J Med. 2013 Nov;126(11):e11-4. doi: 10.1016/j.amjmed.2013.05.025. No abstract available.
• Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available.
• Taylor DO, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Rahmel AO, Kucheryavaya AY, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report--2008. J Heart Lung Transplant. 2008 Sep;27(9):943-56. doi: 10.1016/j.healun.2008.06.017. No abstract available.
• Tomai F, Adorisio R, De Luca L, Pilati M, Petrolini A, Ghini AS, Parisi F, Pongiglione G, Gagliardi MG. Coronary plaque composition assessed by intravascular ultrasound virtual histology: association with long-term clinical outcomes after heart transplantation in young adult recipients. Catheter Cardiovasc Interv. 2014 Jan 1;83(1):70-7. doi: 10.1002/ccd.25054. Epub 2013 Jul 16.
• Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, Nieman K, Bruining N, Dorange C, Miquel-Hebert K, Veldhof S, Webster M, Thuesen L, Dudek D. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet. 2009 Mar 14;373(9667):897-910. doi: 10.1016/S0140-6736(09)60325-1.
• Pighi M, Tomai F, Petrolini A, de Luca L, Tarantini G, Barioli A, Colombo P, Klugmann S, Ferlini M, Ormezzano MF, Loi B, Calabro P, Bianchi RM, Faggian G, Forni A, Vassanelli C, Valgimigli M, Ribichini F. Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study. J Cardiovasc Transl Res. 2016 Feb;9(1):40-8. doi: 10.1007/s12265-015-9665-x. Epub 2015 Dec 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ACTUAL): September 1, 2017
• Study Completion (ACTUAL): December 1, 2020

Study Registration Dates

• First Submitted: February 16, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (ESTIMATE): March 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Bioresorbable Vascular Scaffold; Heart Transplant; Cardiac Allograft Vasculopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CART