Clinical trial NCT02377648: Safety and Efficacy of Everolimus - Eluting Bioresorbable Vascular Scaffold for Cardiac Allograft Vasculopathy
Official title: Everolimus-eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: A Prospective Multicenter Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiac Allograft Vasculopathy
Keywords: Cardiac Allograft Vasculopathy
Heart Transplant
Bioresorbable Vascular Scaffold
Lead sponsor: Universita di Verona
Sponsor class: OTHER
First posted: 2015-03-03
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: One Year
Secondary outcomes:
measure: Device success (lesion based analysis)
timeFrame: Basal procedure
measure: Procedural success (subject based analysis)
timeFrame: Basal procedure
measure: Death (cardiac, vascular, non-cardiovascular)
timeFrame: 30 days, 180 days, 2 years and 3 years
measure: Myocardial infarction (MI: Q wave Myocardial Infarction (QMI)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Target lesion revascularization (TLR)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Target vessel revascularization (TVR)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Non-target vessel revascularization (NTVR)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Composite (Death/All MI/ Graft failure)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Composite (Cardiac death/TV-MI/TLR )
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Composite (Cardiac death/all MI/TLR )
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Composite (Cardiac death/all MI/TVR)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Composite (Death/All MI/all revascularization)
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Scaffold thrombosis
timeFrame: 30 days, 180 days, 1 year, 2 years and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Angiographic Endpoints
timeFrame: Basal procedure, 1 year and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Intravascular Ultrasound/Intravascular Ultrasound-Virtual Histology Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
measure: Optical Coherence Tomography Endpoints
timeFrame: Basal procedure and 3 years
Other outcomes:
Locations:
city: Cagliari
country: Italy
facility: Azienda Ospedaliera Brotzu
city: Naples
country: Italy
facility: Azienda Ospedaliera Specialistica Dei Colli
city: Padua
country: Italy
facility: Azienda Ospedaliera Di Padova
city: Pavia
country: Italy
facility: Fondazione Irccs Policlinico San Matteo
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: European Hospital
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata Di Udine (Asuiud)
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Rotterdam
country: Netherlands
facility: Cardialysis Core Laboratory For Imaging
city: Rotterdam
country: Netherlands
facility: Thoraxcenter, Universtity of Rotterdam
Study officials:
affiliation: Universita di Verona
name: Flavio L Ribichini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universita di Verona
name: Michele Pighi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.