First-in-man experience with the DES Orsiro in the treatment of patients with single de novo...
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Transcript of First-in-man experience with the DES Orsiro in the treatment of patients with single de novo...
First-in-man experience with the DES Orsiro in the treatment of patients with single de novo coronary
artery lesions (BIOFLOW-I)
Martial Hamon, MD, FESCUniversity Hospital of Caen
Normandy, France
ClinicalTrials.gov Identifier: NCT01214148
Speaker’s name: Martial Hamon
I have the following potential conflicts of interest to report: Research contracts Consulting for BIOTRONIK AG Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s)
I do not have any potential conflict of interest
Potential conflicts of interest
Background
• Early generations of DES have reduced restenosis, but have been associated with an increased risk of late events
• Efforts to resolve these problems have been made including improvements in stent platforms, polymer carriers as well as drug selection
• A hybrid combination of active and passive coatings on a DES aim to optimize effectiveness of results and also mediate the threat of late events
• The aim of the BIOFLOW-I study was to evaluate the safety and efficacy of the Orsiro Hybrid Drug Eluting Stent with a bioabsorbable polymer, in patients with a single de novo lesion in a native coronary artery
The device: Orsiro Hybrid Drug Eluting Stent
• PROBIO® passive coating encapsulates the stent and minimizes interaction between the metal stent and the surrounding tissue
• BIOlute® active coating contains a highly biocompatible polymer which delivers a Limus drug via a biodegradable matrix
• PRO-Kinetic Energy Stent System brings good deliverability for reaching complex lesions
BIOlute® achieves acontrolled drug release
The BIOlute® polymer matrix gently degrades into CO2 and H2O
Only a PROBIO® sealed stent is left in the arterial wall
Quick facts
Passive coating PROBIO® amorphous silicon carbide coating
Active coating BIOlute® bioabsorbable PLLA eluting Sirolimus
Drug dose 1.4 µg/mm2
Stent material Cobalt chromium L-605
Strut thickness 60 µm (3.00 mm stent)
Approval status CE approved
Investigational centers & core lab
Principal investigatorRodica Niculescu, MD, PhD, FESCSpitalul Clinic de Urgenţă Bucureşti, Romania
15 Subjects enrolled 100% Angio & IVUS FUP @ 4month100% Angio & IVUS FUP @ 9month
Angiography CorelabRon Waksman MDMedStar Health Research Institute, Washington DC, USA
Principal investigatorDan Deleanu, MD, FESCInstitutul de Urgenţă pentru Boli Cardiovasculare, Romania
15 Subjects enrolled100% Angio FUP @ 4month100% Angio FUP @ 9month
IVUS CorelabNeil J. Weissman MDMedStar Health Research Institute, Washington DC, USA
BIOFLOW-I trial design
Clinical endpoint assessment
Angiographic & IVUS endpoint assessment
30 d 4 mo 9 mo 12 mo 2 yr 3 yr
• Design: Prospective, multi-centre, first in man trial • Patient Number: 30• Patents with angiographic follow-up: 30• Patients with IVUS follow-up: 15• Follow-up rate: 100%• Enrollment time: Between 02 – 23 July 2009
Study endpoints
Primary Endpoint• In-stent late lumen loss at 9 months by QCA
Secondary Endpoints • In-stent and in-segment binary restenosis rate at 4 and 9 months post procedure• Clinically driven target lesion revascularization (TLR) at 1, 4 and 9 months and at 1,
2 and 3 years post-procedure• Composite of cardiac death, MI attributed to the target vessel and clinically driven
target lesion revascularization at 1, 4 and 9 month post-procedure, and yearly up to 3 years
• Stent thrombosis at 1, 4 and 9 months, and at 1, 2 and 3 years post-procedure.Definitions• Lesion Treatment Success is defined as the attainment of <30% residual stenosis
by offline QCA using any percutaneous method• Device Success defined as achievement of a final residual diameter stenosis of
<30% by offline QCA, using the assigned device only
Patient eligibility
Inclusion Criteria• Patient is ≥18 years old• Clinical evidence of ischemic heart disease
and / or a positive functional study. Documented stable angina pectoris, or documented silent ischemia
• Single de novo lesion with ≥50% and <90% stenosis in 1 coronary artery
Exclusion Criteria• Documented left ventricular ejection
fraction (LVEF) ≤ 30%• ACS (NSTE-MI or STEMI)• Three-vessel coronary artery disease• Evidence of myocardial infarction
within 72 hours prior to the index procedure
• Total occlusion (TIMI 0 or 1)• Target lesion is located in or supplied
by an arterial or venous bypass graft• Target lesion involves a side branch
>2.0mm in diameter• Unprotected Left main coronary
artery disease (stenosis >50%)
Baseline clinical characteristics
N=30
Age, years 58.10 yrs ± 9.80
Male sex 60.0% 18/30
Hyperlipidemia 93.3% 28/30
History of MI 73.3% 22/30
Hypertension 66.6% 20/30
Smoker 53.3% 16/30
Diabetes 23.3% 7/30
CHF 20.0% 6/30
Baseline lesion characteristics
Pre-Procedure N=30
RVD (mm) 2.75 ± 0.34
MLD (mm) 0.95 ± 0.29
% Diameter stenosis 65.52 ± 9.47
Mean Lesion length (mm) 11.71 ± 4.40
Procedural N=30
Stent length per lesion (mm) 19.93 ± 5.33
Stent diameter per lesion (mm) 3.08 ± 0.37
Direct stenting 20.0%
Device success* 100.0%* Defined as In-Stent < 30% residual stenosis by offline QCA
Angiographic follow-up results4-month FUP 9-month FUP
RVD (mm) 2.81 ± 0.28 2.81 ± 0.30
Minimal Lumen Diameter In-stent (mm) 2.50 ± 0.36 2.56 ± 0.38
In-segment (mm) 2.20 ± 0.35 2.21 ± 0.31
Diameter Stenosis In-stent (%) 15.19 ± 4.55 13.60 ± 4.27
In-segment (%) 23.66 ± 9.80 23.55 ± 8.06
Late Loss In-stent (mm) 0.12 ± 0.19 0.05 ± 0.22
In-segment (mm) 0.06 ± 0.23 0.05 ± 0.26
Binary Restenosis In-stent (mm) 0% 0%
In-segment (mm) 0% 0%
Cumulative frequency of Diameter Stenosis
Cumulative Frequency of Minimum Lumen Diameter
Cumulative Frequency of In-Stent Late Lumen Loss
Mean In-Stent LLL:4 Months 0.12 ± 0.219 Months 0.05 ± 0.22
9-month clinical results N %Death 0 0.0
Stent thrombosis 0 0.0
MI 0 0.0
TLR (clinically driven) 2 6.7
MACE 2 6.7
Clinical outcomes at 9 months
BIOFLOW-I results in perspective
Overview of in stent late lumen loss in FIM trials
* Randomized trial. Only number of patients in device arm displayed
1 Serruys et al. A randomized comparison of a durable polymer Everolimus-eluting stent with a bare metal coronary stent: The SPIRIT first trial; Eurointervention2 Ormiston et al. Six-month results of the NEVO Res-Elution I (NEVO RES-I) trial: a randomized, multicenter comparison of the NEVO sirolimus-eluting coronary stent with the TAXUS Liberte paclitaxel-eluting stent in de novo native coronary artery lesions; Circ.Cardiovasc.Interv.3 Sousa et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study; Circulation4 Meredith et al. The next-generation Endeavor Resolute stent: 4-month clinical and angiographic results from the Endeavor Resolute first-in-man trial; EuroIntervention5 Meredith et al. Clinical and angiographic results with the next-generation resolute stent system: a prospective, multicenter, first-in-human trial; JACC.Cardiovasc.Interv.
FIM SR3
4 mn=15
NevoNevo Res-I2*
6 mn=186
XienceVSPIRIT First1
6 m n=28
Endeavor Resolute OrsiroBIOFLOW-I9 mn=30
FIM FR3
4 mn=15
FIM4
4 mn=30
FIM5
9 mn=92
Cypher
± 0.21
± 0.31
± 0.30
± 0.26
± 0.27
± 0.22
(mm)
0.10
0.13
0.09
-0.01
0.12
0.22
0.05
BIOFLOW-I Case report Pre-procedural angiography
Medical history & risk factors• Male, 53 yrs• MI (April-2009), smoker,
hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009RCA midLesion length 16 mm
Source: BIOFLOW-i case, patient ROM001-009
BIOFLOW-I Case report Post-procedural angiography
Medical history & risk factors• Male, 53 yrs• MI (April-2009), smoker,
hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009RCA midLesion length 16 mmPost-dilatationStent size 3.5 x 18 mmMax pressure 21 atm
Source: BIOFLOW-i case, patient ROM001-009
BIOFLOW-I Case report Four-month follow-up angiography
Medical history & risk factors• Male, 53 yrs• MI (April-2009), smoker,
hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009RCA midLesion length 16 mmPost-dilatationStent size 3.5 x 18 mmMax pressure 21 atm
Source: BIOFLOW-i case, patient ROM001-009
BIOFLOW-I Case report Nine-month follow-up angiography
Medical history & risk factors• Male, 53 yrs• MI (April-2009), smoker,
hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009RCA midLesion length 16 mmPost-dilatationStent size 3.5 x 18 mmMax pressure 21 atm
Source: BIOFLOW-i case, patient ROM001-009
Study design
– A prospective, multi-centre, single treatment clinical trial
– Endpoint: LLL 9 months, N=30
– A prospective, multi-center, non-inferiority, randomized study, Orsiro vs. Xience Prime
– Endpoint: LLL at 9 months, N=440
– A prospective, multi-centre, single treatment clinical study
– Endpoint: LLL at 9 months, N=120
– A prospective, multi-centre, single treatment clinical registry
– Endpoint: TLF at 9 months, with long term follow-up, N=1000+
– Comparative, non-inferiority trial evaluating safety and efficacy
– Study to evaluate safety and efficacy in a complex patient population
– Post marketing surveillance to demonstrate long term outcomes
– First-in-man study evaluating safety and efficacy, data submitted during CE approval (TÜV)
Clinical strategy
Study design
Clinical strategy
BIOFLOW Clinical Program for Orsiro Hybrid Drug Eluting Stent
Conclusions
• In this FIM study with a primary angiographic endpoint, the Orsiro Hybrid DES showed excellent results in terms of late lumen loss in the overall patient population
• This mixed population of patients is atypical for a FIM study, with its high rate of diabetic patients and complex lesions
• At 9 months follow-up, no late catch-up was seen in the LLL values and a narrow standard deviation suggests that these study results are quite robust
• A larger randomized, comparative study is currently running to prove the safety and effectiveness of this promising device