Outcome of CHAllenging lesioNs and Patients Treated With Polymer Free Drug-CoatEd Stent (CHANCE)

Outcome of CHAllenging lesioNs and Patients Treated With Polymer Free Drug-CoatEd Stent ("Biofreedom"): the CHANCE a Multicenter Study

Length of DAT (Dual Antiplatelet therapy) represents one of the most challenging choices for interventional cardiologist.

Prolonged DAT reduces risk of subsequent MI (Myocardial Infarction) with an increase in major bleedings, consequently with a neutral effect on survival [1].

Recently a Polymer-free Drug-Coated coronary stent has been tested in a randomized controlled trial with only one month of DAT due to its peculiar features, with an increased efficacy compared to BMS (Bare Metal Stent) and with a not negligible risk of ST at one year (about 2%)[2,3].

The RCT despite its promising design (inclusion of high risk patients like those with previous bleeding or with severe renal disease) showed a major limitation, that is:

1. patients who are often offered a Biofreedom in real life, that is those with active cancer or needing major surgery or on OAT (Oral Anticoagulation)
2. and patients with bifurcation and multivessel disease, that is those with an increased risk of ST [4]
3. STEMI patients [5] were underrepresented (less than 30%). Consequently we performed this multicenter study to evaluate safety and efficacy of Biofreedom in real life patients.

POCE (a composite end point of death, myocardial infarction, target lesion revascularization) and DOCE (cardiac death, MI-TLR and TLR) will be the primary end points, while its single components will be the secondary ones along stent thrombosis and with bleedings (Barc classification).

At least 12 months The Leaders FREE (2) reported an incidence of MACE of 9.4% at one year in overall patients. If there is a true difference in favour of the experimental treatment of 1.2%, then 870 patients are required to be 80% sure that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference when compared to non selected patients of more than 2% [5]

All patients implanting Biofreedom with these prespecified analysis:

1. Clinical

   • Diabetic patients (both insulin and not insulin depenent)
   • Requiring oral anticoagulation
   • On active cancer (that is requiring chemio or radio-therapy and or surgery)
   • Requiring surgery
   • STEMI

2. Interventional

   • Bifurcation (both provisional both 2 stents)
   • Multivessel
   • Ostial

Study Overview

• Status: Completed
• Conditions: Coronary Disease; STEMI; Drug Eluting Stent
• Intervention / Treatment: Device: Biofreedom

Detailed Description

Our interest is to test the performance of these stents in real life patients

• Study Type: Observational
• Enrollment (Actual): 1000

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All patients implanting Biofreedom with these prespecified analysis:

1. Clinical

   • Diabetic patients (both insulin and not insulin depenent)
   • Requiring oral anticoagulation
   • On active cancer (that is requiring chemio or radio-therapy and or surgery)
   • Requiring surgery
   • STEMI

2. Interventional

   • Bifurcation (both provisional both 2 stents)
   • Multivessel
   • Ostial

Description

Inclusion Criteria:

1. Clinical

   • Diabetic patients (both insulin and not insulin depenent)
   • Requiring oral anticoagulation
   • On active cancer (that is requiring chemio or radio-therapy and or surgery)
   • Requiring surgery
   • STEMI

2. Interventional

   • Bifurcation (both provisional both 2 stents)
   • Multivessel
   • Ostial

Exclusion

1. clinical less than 18 years old or more than 80
2. interventional last remaing vessel

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Real life patients; Patients who are often offered a Biofreedom in real life, that is those with active cancer or needing major surgery or on OAT (Oral Anticoagulation)	Device: Biofreedom; Use of Biofreedom in real life patients
Difficult coronary lesions; Patients with bifurcation and multivessel disease, that is those with an increased risk of ST	Device: Biofreedom; Use of Biofreedom in real life patients
STEMI; Patients with STEMI	Device: Biofreedom; Use of Biofreedom in real life patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of POCE (primary patient-oriented endpoint)	Incidence of POCE (a composite and mutual exclusive end point of death, myocardial infarction, target lesion revascularization)	At least 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Death	Incidence of Death	At least 6 months
Incidence of Myocardial Infarction	Incidence of Myocardial Infarction	At least 6 months
Incidence of TLR	Incidence of target lesion revascularization	At least 6 months
Incidence of Cardiac Death	Incidence of Cardiac Death	At least 6 months
Incidence of MI-TLR	Incidence of Myocardia Infarction TLR	At least 6 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Investigators: Principal Investigator: Fabrizio D'Ascenzo, Città della Salute e della Scienza di Torino

Publications and helpful links

General Publications

• Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014 Dec 4;371(23):2155-66. doi: 10.1056/NEJMoa1409312. Epub 2014 Nov 16.
• Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrie D, Naber C, Lipiecki J, Richardt G, Iniguez A, Brunel P, Valdes-Chavarri M, Garot P, Talwar S, Berland J, Abdellaoui M, Eberli F, Oldroyd K, Zambahari R, Gregson J, Greene S, Stoll HP, Morice MC; LEADERS FREE Investigators. Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk. N Engl J Med. 2015 Nov 19;373(21):2038-47. doi: 10.1056/NEJMoa1503943. Epub 2015 Oct 14.
• Garot P, Morice MC, Tresukosol D, Pocock SJ, Meredith IT, Abizaid A, Carrie D, Naber C, Iniguez A, Talwar S, Menown IBA, Christiansen EH, Gregson J, Copt S, Hovasse T, Lurz P, Maillard L, Krackhardt F, Ong P, Byrne J, Redwood S, Windhovel U, Greene S, Stoll HP, Urban P; LEADERS FREE Investigators. 2-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents. J Am Coll Cardiol. 2017 Jan 17;69(2):162-171. doi: 10.1016/j.jacc.2016.10.009. Epub 2016 Oct 30.
• D'Ascenzo F, Bollati M, Clementi F, Castagno D, Lagerqvist B, de la Torre Hernandez JM, ten Berg JM, Brodie BR, Urban P, Jensen LO, Sardi G, Waksman R, Lasala JM, Schulz S, Stone GW, Airoldi F, Colombo A, Lemesle G, Applegate RJ, Buonamici P, Kirtane AJ, Undas A, Sheiban I, Gaita F, Sangiorgi G, Modena MG, Frati G, Biondi-Zoccai G. Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses. Int J Cardiol. 2013 Jul 31;167(2):575-84. doi: 10.1016/j.ijcard.2012.01.080. Epub 2012 Feb 22.
• Naber CK, Urban P, Ong PJ, Valdes-Chavarri M, Abizaid AA, Pocock SJ, Fabbiocchi F, Dubois C, Copt S, Greene S, Morice MC; LEADERS FREE Investigators. Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a Leaders Free ACS sub-study. Eur Heart J. 2017 Apr 1;38(13):961-969. doi: 10.1093/eurheartj/ehw203.
• Blackwelder WC. "Proving the null hypothesis" in clinical trials. Control Clin Trials. 1982 Dec;3(4):345-53. doi: 10.1016/0197-2456(82)90024-1.
• Gallone G, D'Ascenzo F, Boccuzzi G, Cortese B, Di Biasi M, Omede P, Capodanno D, Cerrato E, Vicinelli P, Infantino V, Poli A, Ugo F, Conrotto F, Grigis G, Varbella F, Latini RA, D'Urbano M, Montabone A, Senatore G, Ferrara E, D'Amico M, De Ferrari GM, Ielasi A. Real-world reasons and outcomes for 1-month versus longer dual antiplatelet therapy strategies with a polymer-free BIOLIMUS A9-coated stent. Catheter Cardiovasc Interv. 2020 Sep 1;96(3):E248-E256. doi: 10.1002/ccd.28757. Epub 2020 Feb 3.
• D'Ascenzo F, Gallone G, Boccuzzi G, Cortese B, Di Biasi M, Capodanno D, Vicinelli P, Infantino V, Poli A, Grigis G, Varbella F, De Ferrari GM, Ielasi A; Collaborators. Dual antiplatelet therapy strategies and clinical outcomes in patients treated with polymer-free biolimus A9-coated stents. EuroIntervention. 2020 Feb 7;15(15):e1358-e1365. doi: 10.4244/EIJ-D-19-00450.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): January 31, 2018
• Study Completion (ACTUAL): May 1, 2018

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (ACTUAL): August 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease
• Other Study ID Numbers: CHANCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes