Next genera*on DES in bifurca*on PCI Mark Spence Consultant Cardiologist Royal Victoria Hospital, Belfast The CELTIC Bifurca0on Study (Demonstrate equivalence with next genera*on SYNERGY plaKorm and Xience stent in culoMe sten*ng for bifurca*on lesions) 12.2014 CELTIC BIFURCATION
n = 170 pts
01.2016 09.2016 Enrollment & Follow-­‐Up 9m 01.2018 2 Y Popula*on: 170 pa*ents; Medina 1:1:1. 2 stent strategy, Synergy vs Xience Primary Outcome: 9 month composite death, Myocardial Infarc*on, Target Vessel Failure, Stent Thrombosis (angio FU) Principal inves*gator: Prof. David Foley -­‐ Beaumont Hospital, Dublin Co-­‐PI: Dr. Simon Walsh -­‐ Belfast Health & Social Care Trust Study Coordina0on, Management Independent Corelab Analysis Organiza0on of CEC 15 PARTICIPATING SITES Principle Inves5gators : Dr. Simon Walsh Cardiology Department, Belfast Health & Social Care Trust, Belfast, Northern Ireland Prof. David Foley Beaumont Hospital, Dublin, Rep of Ireland Study Inves5gators: Dr. Colm HanraCy Prof. Keith Oldroyd Golden Jubilee Na*onal Hospital, Glasgow City Hospital, Belfast Belfast Dr Jonathan Hill Prof. David Foley Beaumont Hospital, Dublin Dr. Tom Johnson King's College London, London Bristol Royal Infirmary, Bristol Dr Niall Mulvihill Dr Elliot Smith London Chest Hospital, London Dr. Nick Cruden St Vincent Private Hospital, Dublin Edinburgh Royal Infirmary, Edinburgh Dr Rod Stables Liverpool Heat and Chest Hospital, Liverpool Trial Hypothesis Inves*gator ini*ated trial, sponsored by Boston Scien*fic Corpora*on via CERC We hypothesize that modern genera*on DES facilitate good clinical outcomes using a planned 2-­‐stent bifurca*on treatment. •  We an*cipate that bifurca*on culoMe sten*ng with modern DES plaKorms will demonstrate outcomes that are beMer than earlier results from published randomized controlled trials. •  This study will examine outcomes for pa*ents treated by planned culoMe sten*ng and compare outcomes between 2 different stent plaKorms, the Synergy II and the Xience Xpedi*on DES plaKorms. •  The primary outcome measures: clinical and angiographic follow-­‐up parameters assessed at a 9-­‐month *me point. Background •  Conceived and designed while EBC2 study was enrolling Background The EBC TWO Trial Hypothesis “Large true coronary bifurca*on lesions (side branch ≥2.5mm) with significant os*al side branch disease (≥5mm length), are best treated with culoMe sten*ng rather than a provisional T technique, with respect to target vessel revascularisa*on, myocardial infarc*on and death at 12 months.” D Hildick-­‐Smith EuroPCR 2015 EBC 2 RESULTS EuroPCR 2015 Main vessel: Stent N (%) Stent length (mm) Stent diameter (mm) Side branch: Stent N(%) Stent length (mm) Stent diameter (mm) Total stent length (mm) Total number of stents Final kissing balloon infla0on successful Procedural success Procedure 0me (min) Fluoroscopy 0me (min) Diamentor Cost (€) Provisional T (N=103) CuloQe (N=97) 103 (100%) 23.4 ± 4.8 3.06±0.32 16 (16%) 19.87±6.75 2.61±0.29 33.57±17.0 1.6±0.8 97 (94%) 100 (97.09%) 67.81±25.61) 20.05±10.05) 18262±32363 96 (99%) 22.9 ± 5.1 3.03±0.33 94 (97%) 20.67±5.49 2.72±0.25 51.82±20.25 2.5±0.7 93 (96%) 95 (98%) 82.51±38.86) 26.57±17.13) 21291±34547.9 ns 0.08 <0.0001 <0.0001 ns ns 0.0018 0.0011 ns 2257 3263 <0.0001 D Hildick-­‐Smith p ns ns EBC2 PRIMARY ENDPOINT Provisional T (n=103) CuloQe (n=97) 8 (8%) 10 (10%) Death 2 (2%) 1 (1%) Myocardial infarc0on NSTEMI STEMI <48H 5 (5%) 5 0 4 10 (10%) 9 1 10 TVR 3 (3%) 1 (1%) 1 (1%) 1 0 3 (3%) 2 1 Death, MI, TVR at 12 months Stent thrombosis Definite / Probable Possible D Hildick Smith. EuroPCR 2015 The EBC TWO Trial EuroPCR 12 M Outcome : D: eath, MI and TVR at 12 EBC TWO
Statistics Tables
months p=0,5253 1.00
Survival Distribution Function
0.75
0.50
0.25
0.00
0
2
4
6
8
Follow-up time (months)
STRATA:
group=A. Simple Strategy
group=B. Complex Strategy
10
12
D Hildick Smith Censored group=A. Simple Strategy
Censored group=B. Complex Strategy
CELTIC context •  NORDIC/BBC pooled: MACE + TVR at 9 months –  17.3% for complex vs 10.1% for simple •  EBC2 : MACE + TVR at 12 months –  10% for culoMe vs 8% for simple •  Periprocedural MI big factor for 2 stent strategy •  Role for improvement –  Technique, stent plaKorm, drug and polymer The CELTIC Bifurca0on Study (Demonstrate equivalence with next genera*on SYNERGY plaKorm and Xience stent in culoMe sten*ng for bifurca*on lesions)
Study Aims •  Hypothesis genera*ng •  Non-­‐inferiority (synergy 2 vs xience expedi*on) •  Evaluate op*mal culoMe outcomes with modern DES in true 1,1,1 bifurca*on lesions •  If event rates substan*ally lower than in EBC2 poten*ally provide ra*onale for a defini*ve conserva*ve vs culoMe EBC3 study using best in class DES Inclusion Criteria •  Subject will be included if all of the following criteria are met: 1. Male or female pa*ent >18 years old 2. Females of childbearing poten*al with a nega*ve pregnancy test 3. Coronary artery disease requiring revasculariza*on that is amenable to PCI 4. Medina 1,1,1 bifurca*on lesion with >70% lesion in both the main vessel and the side branch by visual assessment 5. Main branch and side branch ≥ 2.5mm in diameter by visual assessment 6. Both vessels require sten*ng in the opinion of the operator Exclusion Criteria Subject will not be included if any one of the following condi0ons exists: 1. Acute myocardial infarc*on with ongoing ST-­‐eleva*on 2. Cardiogenic shock 3. Lesion involves the lev main coronary artery 4. Lesion involves bypass grav 5. Plan to treat >1 other coronary vessel at the *me of inclusion 6. Chronic total occlusion of any target vessel 7. Lev ventricular ejec*on frac*on <20% 8. Requirement for ongoing haemodialysis 9. Life-­‐expectancy limited to <12 months due to co-­‐morbid condi*on 10. Known allergy to Aspirin 11. Known allergy to Clopidorel and Prasugrel and Ticagrelor 12. Known allergy to stent drug elutant 13. Known allergy to any other component of either the Synergy II or Xience Xpedi*on stents systems 14. Ongoing par*cipa*on in another inves*ga*onal device or drug study 15. Inability to provide informed consent Follow-­‐up •  Total dura*on for each subject: 24 months •  All enrolled subjects will be evaluated at 6 months, 9 months, and 2 years •  An office visit is required for the 9 month follow-­‐up. •  All other protocol required follow-­‐up assessments :
telephone interview or office visit as per local prac*ce and subjects’ mobility •  All subjects will undergo angiographic follow-­‐up during the 9-­‐month follow-­‐up visit. •  Es0mated dura0on of enrollment: 12 months •  Total es0mated dura0on of Study: 43 months (study ini*a*on: 4 months; recruitment: 12 months; follow up: 24 months; close-­‐out: 3 months) CuloMe steps SB & MB pre-­‐dilated Start with side branch stent ideally Stent according to vessel distal diameter POT (mandatory) sized to MB Rewire main vessel (distal strut) Dilate and stent main vessel POT (mandatory) sized to MB Rewire side branch Stent from just before carina to beyond distal lesion NC infla*ons sized to daughter vessel diameter (mandatory) High pressure individual (e.g. 20 atm; encouraged) –  Kissing infla*ons (NC) to nominal pressure (mandatory) –  Final single post dil of stents prox to bifurca*on (discre0onary) –  IVUS / OCT encouraged –
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Primary Endpoint(s) At 9 months follow up composite of: Death Myocardial Infarc*on CVA Target Vessel Failure (Composite of Target Vessel Revasculariza*on and Target Vessel inadequacy) •  Definite or Probable stent thrombosis (ARC criteria) •  Binary angiographic restenosis •
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Secondary Endpoints Predefined Secondary Procedural Endpoints •  Technical success (deployment of stents in both branches with <20% residual stenosis and kissing balloon infla*on at end of procedure) •  Total procedure *me •  Total radia*on dose •  Total contrast dose •  Need to use secondary equipment or manoeuvres to complete the case (extra support guidewires, anchor balloons or mother & daughter catheter) •  Evidence of longitudinal stent compression at index implanta*on •  Evidence of stent fracture at angiographic follow-­‐up Clinical Endpoints at 24 months Composite of: • Death • Myocardial Infarc*on • CVA • Target Vessel Failure (Composite of Target Vessel Revasculariza*on and Target Vessel Inadequacy) • Definite or Probable stent thrombosis (ARC criteria) Enrollment Recruitment per month
Recruitment per site
Power Calcula*on On the basis Nordic and pooled Nordic/BBC1 and allowing for improved clinical outcomes with modern genera*on DES combined primary endpoint that includes death, myocardial infarc*on, target vessel revasculariza*on, target vessel failure, stent thrombosis (definite or probable) or binary angiographic restenosis at 9 months will be an*cipated to be 10%. • We expect Synergy stent will offer no worse than equivalent performance to the Xience stent. • Therefore, on the basis of a non-­‐inferiority power calcula*on for a binary outcome study (allowing for a 20% drop-­‐out rate for follow-­‐up angiography) 85 pa*ents will be required per group. This sets a significance level (𝛂) of 5% with a power (1-­‐β) of 90% and a non-­‐inferiority limit of 15%. This allows for an upper limit of a one-­‐sided 95% confidence interval (or equivalently a 90% two-­‐sided confidence interval).