Original article
Italian Diffuse/Multivessel Disease ABSORB Prospective Registry (IT-DISAPPEARS). Study Design and Rationale Luca Testa, Giuseppe Biondi Zoccai, Fabrizio Tomai, Flavio Ribichini, Ciro Indolfi, Corrado Tamburino, Antonio Bartorelli, Anna Sonia Petronio, Francesco Bedogni and Marco De Carlo Background The Absorb Bioresorbable Vascular Scaffold System (Absorb BVS) is an everolimus-eluting bioresorbable vascular scaffold able to provide temporary scaffolding and antiproliferative drug delivery for the treatment of coronary artery disease. This temporary scaffolding could be the true feature to overcome the limitations of the conventional metallic stents. A growing body of evidence worldwide is supporting its implementation into daily practice as being associated with comparable results as the second-generation everolimuseluting stent. However, these pieces of evidence come from ‘studies in which the majority of the patients had low-risk stenoses’, whereas patients with more complex coronary artery disease could benefit the most from the Absorb BVS technology. Methods The aim of the IT-DISAPPEARS is to investigate the procedural and clinical performance of the Absorb BVS in patients with long (>24 mm), single-vessel coronary disease or with multivessel disease. At least 50 centers across the Italian territory will enroll 1000 patients with either stable or acute coronary syndromes. Follow-up will
Introduction In 1977, Andreas Gru¨ntzig performed the first ‘plain old balloon angioplasty’ (POBA). Coronary stents, which were first developed in the mid1980s,1 have replaced the POBA after the observed improvements in angiographic and clinical outcomes.2,3 They then became widely implemented after the publication of the landmark Belgian Netherlands Stent4 and Stent Restenosis Study5 trials, together with evidence indicating the benefit of using dual antiplatelet therapy (Dual Antiplatelet Therapy)6–8 and/or adequate stent deployment.9 By 1999, coronary stenting was performed in 84.2% of percutaneous coronary intervention (PCI) procedures.10 It was the attempt to minimize this in-stent neointimal hyperplasia, and thereby reduce rates of repeat revascularization,11–14 that led to the development of drug-eluting stents (DES). The dramatic reduction in restenosis rates seen with the use of DES drove the exponential growth of PCI.15–20 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
end up at 5 years. Primary endpoint will be the cumulative hierarchical incidence of major adverse cardiac events at 1 year, defined as: cardiac death, nonfatal target vessel myocardial infarction, or clinically driven target lesion revascularization. The efficacy as well as safety parameters will be evaluated along with a detailed evaluation of the dual antiplatelet therapy duration/interruption. Conclusion The IT-DISAPPEARS could provide the first evidence worldwide concerning the performance of Absorb BVS in patients with high-risk diffuse coronary disease. J Cardiovasc Med 2015, 16:253–258
Istituto Clinico S. Ambrogio, Milan, Italy (TL, BF), La Sapienza Univ, Roma, Italy (BZG), European Hospital, Rome (TF), University of Verona, Verona, Italy (RF), Magna Grecia Univ., Catanzaro, Italy (IC); Ferrarotto Hospital, Catania, Italy,(TC), Centro Cardiologico Monzino, Milan, Italy (BA); Pisa Univ, Pisa, Italy (PAS, DCM) Correspondence to Dr Luca Testa, MD, PhD, Department of Cardiology, Istituto Clinico S. Ambrogio, 20149 Milan, Italy E-mail: [email protected] Received 4 January 2014 Revised 21 August 2014 Accepted 26 August 2014
Even DES, however, have some short- and long-term limitations, given as follows: a still unclear duration of DAPT, which is strongly linked to the risk of stent thrombosis; the preclusion of surgical revascularization; the jailing of side branches; the impairment of noninvasive imaging of coronary arteries with multislice computed tomography and magnetic resonance; and the limited physiology restoration for the treated segment. The Absorb Bioresorbable Vascular Scaffold System (Absorb BVS; Abbott Vascular, Temecula, USA) is a bioresorbable poly (L-lactide) (PLLA) scaffold with a drug and bioresorbable polymer coating [formulation of everolimus in a bioresorbable poly (D,L-lactide) (PDLLA) coating]. The transient nature of the Absorb BVS reduces the potential for late inflammation and thrombosis, which may subsequently reduce the need for long-term DAPT, permit late expansive remodeling of tissue and the return of natural vasomotion, as well as provide compatibility with a broader range of diagnostic imaging technologies. DOI:10.2459/JCM.0000000000000219
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
254 Journal of Cardiovascular Medicine 2015, Vol 16 No 3
The Absorb BVS medical device is CE-marked since 14 December 2010. The Abbott Vascular ABSORB Clinical Program currently has one completed clinical trial (ABSORB Cohort A),21 three on clinical follow-up [ABSORB Cohort B,22 ABSORB EXTEND, and ABSORB II randomized controlled trial (RCT)], and two that are actively enrolling (ABSORB FIRST and ABSORB III). To date, the ABSORB Cohort A, ABSORB Cohort B, and ABSORB EXTEND clinical trials have provided short- and preliminary long-term data on the safety and performance of Absorb BVS.
The IT-DISAPPEARS trial is investigator-initiated, and the Societa` Italiana di Cardiologia Invasiva/Gruppo Italiano Studi Emodinamici (SICI-GISE) is the only sponsor of the trial. A scientific restricted grant is provided by Abbott Vascular to SICI-GISE. Such a grant has been and will be used for the study management and for the patients’ fee (200 Euros), while the BVS will be regularly purchased by the enrolling centers. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.
A common feature of these trials is that they enrolled a population in which the majority of the lesions were at relatively low risk.
The IT-DISAPPEARS is registered with ClinicalTrials.gov number NCT02004730.
The hypothesis of the IT-DISAPPEARS is that the potential benefit of the Absorb BVS technology could be maximized in patients with high-risk coronary lesions, that is, those lesions in which the rate of clinically meaningful restenosis and target lesion revascularization, target vessel revascularization (TVR), and major adverse events is higher.23
Methods Oversight
The IT-DISAPPEARS is initiated and managed by the Department of Cardiology of the Istituto Clinico S. Ambrogio in Milan and the Department of Cardiology of the Ospedale Cisanello/University of Pisa in Pisa under the auspices of the Italian Society of Interventional Cardiology. The latter has the property and the responsibility of the entire database. Single centers have unrestricted access to their own patients’ data. A Steering Committee, a Clinical Event Committee and a Data and Safety Monitoring Board (DSMB) will be established to conduct and monitor the study for its entire duration. The Steering Committee is the main policy- and decision-making committee of the study and has the final responsibility for the scientific conduct of the study. An independent Clinical Event Committee is constituted to adjudicate all endpoint-related events (Chairman Dr F. Tomai, Co-Chairman Dr A. Latib and Dr S. Geraci). Regular independent monitoring of the trial data is scheduled. An independent DSMB of acknowledged experts in related fields, not otherwise associated with the trial, will be established to act as a senior advisory board on policy matters. The DSMB will be established among colleagues of those centers that are not participating in the study. The committee watches over the ethics of the conduct of the study in accordance with the Declaration of Helsinki. No formal interim data analysis is anticipated. All trial data are de-identified and registered in a webbased dedicated trial database according to Good Clinical Practice standards.
Trial design
The IT-DISAPPEARS is a prospective registry to evaluate the efficacy and performance of the ABSORB everolimus-eluting bioresorbable vascular scaffold (Absorb BVS revision 1.1) in the treatment of multivessel coronary artery disease (at least two significant stenosis in two different coronary arteries) or long (>24 mm) singlevessel disease. The trial is conducted in accordance with the Clinical Investigational Plan, the Declaration of Helsinki and the applicable local legislations. The conduct of the trial has been approved by the local Ethics Committee at each site. Patient selection
Consecutive patients from the general all-comer interventional cardiology population will be screened for inclusion/exclusion criteria. Compliance with the Instructions for Use (IFU) of the Absorb scaffold is mandatory. The IT-DISAPPEARS will enroll a total of 1000 patients according to inclusion and exclusion criteria listed in Table 1. The trial has enrolled the first patient in December 2013. Informed consent
All participating patients will provide informed consent using the approved informed consent form. The elective PCI patients are completely informed and sign the informed consent form prior to the start of the procedure. In case of an emergency PCI, when there are physical and/or time limitations to provide full written informed consent, the informed consent procedure is altered. In such cases, patients are orally informed about the nature of the study by one of the investigators, witnessed by independent catheterization laboratory personnel. After the procedure, written consent form is obtained. The final eligibility for the trial is based on the preintervention angiography. General strategy
The study scaffolds/stents are inspected and used according to the IFU. The length and diameter of the device to
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
IT-DISAPPEARS trial rationale and study design Testa et al. 255
Table 1
Inclusion and exclusion criteria
Inclusion criteria
Exclusion criteria
Patient must be at least 18 years of age at the time of signing the informed consent form 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 Patient must have indication to percutaneous coronary intervention for multivessel disease (at least two significant stenoses in two different main vessels) and long (>24 mm) single-vessel disease following: stable angina with evidence of myocardial ischemia with stress echocardiography/myocardial SPECT/ exercise test, or unstable angina/non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction with de-novo culprit lesion A ‘hybrid BVS-other DES’ approach is acceptable under the following situations: In patients with two-vessel disease, the longest lesion must be treated with the BVS; In patients with three-vessel disease, 2 vessels must be treated with BVS; The use of a everolimus DES is recommended in case of hybrid treatment Known intolerance to any of the device components Contraindication to dual antiplatelet therapy (DAPT) Lesion in a saphenous vein graft Lesion to left internal mammary artery Unprotected left main stenosis Woman with childbearing potential Age
Italian Diffuse/Multivessel Disease ABSORB Prospective Registry (IT-DISAPPEARS). Study Design and Rationale Luca Testa, Giuseppe Biondi Zoccai, Fabrizio Tomai, Flavio Ribichini, Ciro Indolfi, Corrado Tamburino, Antonio Bartorelli, Anna Sonia Petronio, Francesco Bedogni and Marco De Carlo Background The Absorb Bioresorbable Vascular Scaffold System (Absorb BVS) is an everolimus-eluting bioresorbable vascular scaffold able to provide temporary scaffolding and antiproliferative drug delivery for the treatment of coronary artery disease. This temporary scaffolding could be the true feature to overcome the limitations of the conventional metallic stents. A growing body of evidence worldwide is supporting its implementation into daily practice as being associated with comparable results as the second-generation everolimuseluting stent. However, these pieces of evidence come from ‘studies in which the majority of the patients had low-risk stenoses’, whereas patients with more complex coronary artery disease could benefit the most from the Absorb BVS technology. Methods The aim of the IT-DISAPPEARS is to investigate the procedural and clinical performance of the Absorb BVS in patients with long (>24 mm), single-vessel coronary disease or with multivessel disease. At least 50 centers across the Italian territory will enroll 1000 patients with either stable or acute coronary syndromes. Follow-up will
Introduction In 1977, Andreas Gru¨ntzig performed the first ‘plain old balloon angioplasty’ (POBA). Coronary stents, which were first developed in the mid1980s,1 have replaced the POBA after the observed improvements in angiographic and clinical outcomes.2,3 They then became widely implemented after the publication of the landmark Belgian Netherlands Stent4 and Stent Restenosis Study5 trials, together with evidence indicating the benefit of using dual antiplatelet therapy (Dual Antiplatelet Therapy)6–8 and/or adequate stent deployment.9 By 1999, coronary stenting was performed in 84.2% of percutaneous coronary intervention (PCI) procedures.10 It was the attempt to minimize this in-stent neointimal hyperplasia, and thereby reduce rates of repeat revascularization,11–14 that led to the development of drug-eluting stents (DES). The dramatic reduction in restenosis rates seen with the use of DES drove the exponential growth of PCI.15–20 1558-2027 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
end up at 5 years. Primary endpoint will be the cumulative hierarchical incidence of major adverse cardiac events at 1 year, defined as: cardiac death, nonfatal target vessel myocardial infarction, or clinically driven target lesion revascularization. The efficacy as well as safety parameters will be evaluated along with a detailed evaluation of the dual antiplatelet therapy duration/interruption. Conclusion The IT-DISAPPEARS could provide the first evidence worldwide concerning the performance of Absorb BVS in patients with high-risk diffuse coronary disease. J Cardiovasc Med 2015, 16:253–258
Istituto Clinico S. Ambrogio, Milan, Italy (TL, BF), La Sapienza Univ, Roma, Italy (BZG), European Hospital, Rome (TF), University of Verona, Verona, Italy (RF), Magna Grecia Univ., Catanzaro, Italy (IC); Ferrarotto Hospital, Catania, Italy,(TC), Centro Cardiologico Monzino, Milan, Italy (BA); Pisa Univ, Pisa, Italy (PAS, DCM) Correspondence to Dr Luca Testa, MD, PhD, Department of Cardiology, Istituto Clinico S. Ambrogio, 20149 Milan, Italy E-mail: [email protected] Received 4 January 2014 Revised 21 August 2014 Accepted 26 August 2014
Even DES, however, have some short- and long-term limitations, given as follows: a still unclear duration of DAPT, which is strongly linked to the risk of stent thrombosis; the preclusion of surgical revascularization; the jailing of side branches; the impairment of noninvasive imaging of coronary arteries with multislice computed tomography and magnetic resonance; and the limited physiology restoration for the treated segment. The Absorb Bioresorbable Vascular Scaffold System (Absorb BVS; Abbott Vascular, Temecula, USA) is a bioresorbable poly (L-lactide) (PLLA) scaffold with a drug and bioresorbable polymer coating [formulation of everolimus in a bioresorbable poly (D,L-lactide) (PDLLA) coating]. The transient nature of the Absorb BVS reduces the potential for late inflammation and thrombosis, which may subsequently reduce the need for long-term DAPT, permit late expansive remodeling of tissue and the return of natural vasomotion, as well as provide compatibility with a broader range of diagnostic imaging technologies. DOI:10.2459/JCM.0000000000000219
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
254 Journal of Cardiovascular Medicine 2015, Vol 16 No 3
The Absorb BVS medical device is CE-marked since 14 December 2010. The Abbott Vascular ABSORB Clinical Program currently has one completed clinical trial (ABSORB Cohort A),21 three on clinical follow-up [ABSORB Cohort B,22 ABSORB EXTEND, and ABSORB II randomized controlled trial (RCT)], and two that are actively enrolling (ABSORB FIRST and ABSORB III). To date, the ABSORB Cohort A, ABSORB Cohort B, and ABSORB EXTEND clinical trials have provided short- and preliminary long-term data on the safety and performance of Absorb BVS.
The IT-DISAPPEARS trial is investigator-initiated, and the Societa` Italiana di Cardiologia Invasiva/Gruppo Italiano Studi Emodinamici (SICI-GISE) is the only sponsor of the trial. A scientific restricted grant is provided by Abbott Vascular to SICI-GISE. Such a grant has been and will be used for the study management and for the patients’ fee (200 Euros), while the BVS will be regularly purchased by the enrolling centers. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.
A common feature of these trials is that they enrolled a population in which the majority of the lesions were at relatively low risk.
The IT-DISAPPEARS is registered with ClinicalTrials.gov number NCT02004730.
The hypothesis of the IT-DISAPPEARS is that the potential benefit of the Absorb BVS technology could be maximized in patients with high-risk coronary lesions, that is, those lesions in which the rate of clinically meaningful restenosis and target lesion revascularization, target vessel revascularization (TVR), and major adverse events is higher.23
Methods Oversight
The IT-DISAPPEARS is initiated and managed by the Department of Cardiology of the Istituto Clinico S. Ambrogio in Milan and the Department of Cardiology of the Ospedale Cisanello/University of Pisa in Pisa under the auspices of the Italian Society of Interventional Cardiology. The latter has the property and the responsibility of the entire database. Single centers have unrestricted access to their own patients’ data. A Steering Committee, a Clinical Event Committee and a Data and Safety Monitoring Board (DSMB) will be established to conduct and monitor the study for its entire duration. The Steering Committee is the main policy- and decision-making committee of the study and has the final responsibility for the scientific conduct of the study. An independent Clinical Event Committee is constituted to adjudicate all endpoint-related events (Chairman Dr F. Tomai, Co-Chairman Dr A. Latib and Dr S. Geraci). Regular independent monitoring of the trial data is scheduled. An independent DSMB of acknowledged experts in related fields, not otherwise associated with the trial, will be established to act as a senior advisory board on policy matters. The DSMB will be established among colleagues of those centers that are not participating in the study. The committee watches over the ethics of the conduct of the study in accordance with the Declaration of Helsinki. No formal interim data analysis is anticipated. All trial data are de-identified and registered in a webbased dedicated trial database according to Good Clinical Practice standards.
Trial design
The IT-DISAPPEARS is a prospective registry to evaluate the efficacy and performance of the ABSORB everolimus-eluting bioresorbable vascular scaffold (Absorb BVS revision 1.1) in the treatment of multivessel coronary artery disease (at least two significant stenosis in two different coronary arteries) or long (>24 mm) singlevessel disease. The trial is conducted in accordance with the Clinical Investigational Plan, the Declaration of Helsinki and the applicable local legislations. The conduct of the trial has been approved by the local Ethics Committee at each site. Patient selection
Consecutive patients from the general all-comer interventional cardiology population will be screened for inclusion/exclusion criteria. Compliance with the Instructions for Use (IFU) of the Absorb scaffold is mandatory. The IT-DISAPPEARS will enroll a total of 1000 patients according to inclusion and exclusion criteria listed in Table 1. The trial has enrolled the first patient in December 2013. Informed consent
All participating patients will provide informed consent using the approved informed consent form. The elective PCI patients are completely informed and sign the informed consent form prior to the start of the procedure. In case of an emergency PCI, when there are physical and/or time limitations to provide full written informed consent, the informed consent procedure is altered. In such cases, patients are orally informed about the nature of the study by one of the investigators, witnessed by independent catheterization laboratory personnel. After the procedure, written consent form is obtained. The final eligibility for the trial is based on the preintervention angiography. General strategy
The study scaffolds/stents are inspected and used according to the IFU. The length and diameter of the device to
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
IT-DISAPPEARS trial rationale and study design Testa et al. 255
Table 1
Inclusion and exclusion criteria
Inclusion criteria
Exclusion criteria
Patient must be at least 18 years of age at the time of signing the informed consent form 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 Patient must have indication to percutaneous coronary intervention for multivessel disease (at least two significant stenoses in two different main vessels) and long (>24 mm) single-vessel disease following: stable angina with evidence of myocardial ischemia with stress echocardiography/myocardial SPECT/ exercise test, or unstable angina/non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction with de-novo culprit lesion A ‘hybrid BVS-other DES’ approach is acceptable under the following situations: In patients with two-vessel disease, the longest lesion must be treated with the BVS; In patients with three-vessel disease, 2 vessels must be treated with BVS; The use of a everolimus DES is recommended in case of hybrid treatment Known intolerance to any of the device components Contraindication to dual antiplatelet therapy (DAPT) Lesion in a saphenous vein graft Lesion to left internal mammary artery Unprotected left main stenosis Woman with childbearing potential Age
