A randomized, prospective, intercontinental evaluation of a bioresorbable polymer sirolimus-eluting coronary stent system: the CENTURY II (Clinical Evaluation of New Terumo Drug-Eluting Coronary Stent System in the Treatment of Patients with Coronary Artery Disease) trial

Shigeru Saito, Mariano Valdes-Chavarri, Gert Richardt, Raul Moreno, Andrés Iniguez Romo, Emanuele Barbato, Didier Carrie, Kenji Ando, Bela Merkely, Ran Kornowski, Hélène Eltchaninoff, Stefan James, William Wijns, CENTURY II Investigators, Shigeru Saito, Mariano Valdes-Chavarri, Gert Richardt, Raul Moreno, Andrés Iniguez Romo, Emanuele Barbato, Didier Carrie, Kenji Ando, Bela Merkely, Ran Kornowski, Hélène Eltchaninoff, Stefan James, William Wijns, CENTURY II Investigators

Abstract

Aim: The aim of this study was to establish safety and efficacy of a new sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES). Sirolimus-eluting stent with bioresorbable polymer was compared with everolimus-eluting, permanent polymer, Xience stent (PP-EES) in the frame of a CENTURY II clinical trial designed to make global clinical data compliant with regulatory requirements in Europe and Japan.

Methods and results: The CENTURY II is a prospective, multicentre, randomized (1 : 1), single blind, controlled, non-inferiority clinical trial conducted at 58 study sites in Japan, Europe, and Korea. A total of 1123 patients requiring a percutaneous coronary intervention (PCI) procedure, with implantation of drug-eluting stent (DES), were enrolled [total population (TP)]. Randomization of patients was stratified for the subset of patients matching requirements for DES in Japan (Cohort JR, n = 722). Baseline patient demographic and angiographic characteristics were similar in both study arms, with minimal differences between the TP and Cohort JR. The primary endpoint, freedom from target lesion failure (TLF) at 9 months-TLF [composite of cardiac death, target-vessel-related myocardial infarction (MI) and target lesion revascularization]-was 95.6% with BP-SES and 95.1% with PP-EES (Pnon-inferiority<0.0001). Composite of cardiac death and MI rate was 2.9 and 3.8% (P = 0.40) and target vessel revascularization was 4.5% with BP-SES and 4.2% with PP-EES (P = 0.77). The stent thrombosis rate was 0.9% in both arms. In Cohort JR, freedom from TLF was 95.9 and 94.6% (Pnon-inferiority < 0.0005) with BP-SES and PP-EES, respectively.

Conclusion: The new bioresorbable polymer sirolimus-eluting stent showed safety and efficacy profiles similar to durable polymer everolimus-eluting stent at 9-month follow-up.

Study registration number: UMIN000006940.

Keywords: Bioresorbable polymer; Drug-eluting stent; Everolimus; Randomized trial; Sirolimus.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Figures

Figure 1
Figure 1
Study flowchart. *Japanese requirement (JR): patients who met criteria matching approved indication for drug-eluting stent in Japan; **1101 patients analysed per protocol for total population−22 major protocol deviations (details in Supplementary material online, Appendix); ***715 patients analysed per protocol for cohort JR−9 major protocol deviations.
Figure 2
Figure 2
Century II Cumulative event rates for target lesion failure composite.
Figure 3
Figure 3
Subgroup analysis outcome: relative risk with 95% CI of target lesion failure composite (no. of events/no. of subjects, P-values).

References

    1. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315–1323.
    1. Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Mahaffey KW, Cutlip DE, Fitzgerald PJ, Sood P, Su X, Lansky AJ. SPIRIT III Investigators. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomised trial. JAMA. 2008;299:1903–1913.
    1. Jeremias A, Kirtane A. Balancing efficacy and safety of drug-eluting stents in patients undergoing percutaneous coronary intervention. Ann Intern Med. 2008;148:234–238.
    1. Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabaté M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, Petronio AS, Nordmann AJ, Diem P, Meier B, Zwahlen M, Reichenbach S, Trelle S, Windecker S, Jüni P. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet. 2007;370:937–948.
    1. Camenzind E, Steg PG, Wijns W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation. 2007;115:1440–1455.
    1. Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007;356:998–1008.
    1. Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L SCAAR Study Group. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med. 2007;356:1009–1019.
    1. Van Beusekom HM, Saia F, Zindler JD, Lemos PA, Swager-Ten Hoor SL, van Leeuwen MA, de Feijter PJ, Serruys PW, van der Giessen WJ. Drug-eluting stents show delayed healing: paclitaxel more pronounced than sirolimus. Eur Heart J. 2007;28:974–979.
    1. Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol. 2007;27:1500–1510.
    1. Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007;115:2435–2441.
    1. Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation. 2004;109:701–705.
    1. Gada H, Kirtane AJ, Newman W, Sanz M, Hermiller JB, Mahaffey KW, Cutlip DE, Sudhir K, Hou L, Koo K, Stone GW. 5-Year Results of a Randomized Comparison of XIENCE V Everolimus-Eluting and TAXUS Paclitaxel-Eluting Stents: Final Results From the SPIRIT III Trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) JACC Cardiovasc Interv. 2013;6:1263–1266.
    1. Serruys PW, Ruygrok P, Neuzner J, Piek JJ, Seth A, Schofer JJ, Richardt G, Wiemer M, Carrié D, Thuesen L, Boone E, Miquel-Herbert K, Daemen J. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent: the SPIRIT II trial. EuroIntervention. 2006;2:286–294.
    1. Stone GW, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R, Doostzadeh J, Cao S, Simonton CA, Sudhir K, Lansky AJ, Cutlip DE, Kereiakes DJ SPIRIT IV Investigators. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med. 2010;362:1663–1674.
    1. Smits PC, Hofma S, Togni M, et al. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. Lancet. 2013;381:651–660.
    1. Kolh P, Wijns W, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, Taggart D Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI) Guidelines on myocardial revascularization. Eur Heart J. 2010;31:2501–2555.
    1. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736–2747.
    1. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115:2344–2351.
    1. Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG CONSORT Group. Reporting of non-inferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012;308:2594–2604.
    1. He Y, Maehara A, Mintz GS, Bharaj H, Castellanos C, Kesanakurthy S, Wu X, Guo N, Choi SY, Leon MB, Stone GW, Mehran R, Rabbani LE, Moses JW. Intravascular ultrasound assessment of cobalt chromium versus stainless steel drug-eluting stent expansion. Am J Cardiol. 2010;105:1272–1275.
    1. Farb A, Boam AB. Stent thrombosis redux: the FDA perspective. N Engl J Med. 2007;356:984–987.
    1. Daemen J, Simoons ML, Wijns W, Bagust A, Bos G, Bowen JM, Braunwald E, Camenzind E, Chevalier B, Dimario C, Fajadet J, Gitt A, Guagliumi G, Hillege HL, James S, Jüni P, Kastrati A, Kloth S, Kristensen SD, Krucoff M, Legrand V, Pfisterer M, Rothman M, Serruys PW, Silber S, Steg PG, Tariah I, Wallentin L, Windecker SW, Aimonetti A, Allocco D, Baczynska A, Bagust A, Berenger M, Bos G, Boam A, Bowen JM, Braunwald E, Calle JP, Camenzind E, Campo G, Carlier S, Chevalier B, Daemen J, de Schepper J, Di Bisceglie G, Dimario C, Dobbels H, Fajadet J, Farb A, Ghislain JC, Gitt A, Guagliumi G, Hellbardt S, Hillege HL, Ten Hoedt R, Isaia C, James S, de Jong P, Jüni P, Kastrati A, Klasen E, Kloth S, Kristensen SD, Krucoff M, Legrand V, Lekehal M, Lenarz L, Ni Mhullain F, Nagai H, Patteet A, Paunovic D, Pfisterer M, Potgieter A, Purdy I, Raveau-Landon C, Rothman M, Serruys PW, Silber S, Simoons ML, Steg PG, Tariah I, Ternstrom S, Van Wuytswinkel J, Waliszewski M, Wallentin L, Wijns W, Windecker SW ESC Forum on Drug Eluting Stents European Heart House. Eur Heart J. 2009;30:152–161. Nice, 27–28 September 2007.
    1. Serruys PW, Silber S, Garg S, van Geuns RJ, Richardt G, Buszman PE, Kelbaek H, van Boven AJ, Hofma SH, Linke A, Klauss V, Wijns W, Macaya C, Garot P, DiMario C, Manoharan G, Kornowski R, Ischinger T, Bartorelli A, Ronden J, Bressers M, Gobbens P, Negoita M, van Leeuwen F, Windecker S. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med. 2010;363:136–146.
    1. Natsuaki M, Kozuma K, Morimoto T, Kadota K, Muramatsu T, Nakagawa Y, Akasaka T, Igarashi K, Tanabe K, Morino Y, Ishikawa T, Nishikawa H, Awata M, Abe M, Okada H, Takatsu Y, Ogata N, Kimura K, Urasawa K, Tarutani Y, Shiode N, Kimura T NEXT Investigators. Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent: a randomized, controlled, non-inferiority trial. J Am Coll Cardiol. 2013;62:181–190.
    1. Serruys PW, Farooq V, Kalesan B, de Vries T, Buszman P, Linke A, Ischinger T, Klauss V, Eberli F, Wijns W, Morice MC, Di Mario C, Corti R, Antoni D, Sohn HY, Eerdmans P, Rademaker-Havinga T, van Es GA, Meier B, Jüni P, Windecker S. Improved Safety and Reduction in Stent Thrombosis Associated With Biodegradable Polymer-Based Biolimus-Eluting Stents Versus Durable Polymer-Based Sirolimus-Eluting Stents in Patients With Coronary Artery Disease. Final 5-Year Report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) Randomized, Noninferiority Trial. JACC Cardiovasc Interv. 2013;6:777–789.
    1. Stefanini GG, Byrne RA, Serruys PW, de Waha A, Meier B, Massberg S, Jüni P, Schömig A, Windecker S, Kastrati A. Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials. Eur Heart J. 2012;33:1214–1222.
    1. Palmerini T, Biondi-Zoccai G, Della Riva D, Mariani A, Sabaté M, Smits PC, Kaiser C, D'Ascenzo F, Frati G, Mancone M, Genereux P, Stone GW. Clinical outcomes with bioabsorbable polymer-versus durable polymer-based drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol. 2014;63:299–307.
    1. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48:193–202.
    1. Mauri L, Orav EJ, Candia SC, Cutlip DE, Kuntz RE. Robustness of late lumen loss in discriminating drug-eluting stents across variable observational and randomized trials. Circulation. 2005;112:2833–2839.
    1. Uchida T, Ikeno F, Ikeda K, Suzuki Y, Todaka K, Yokoi H, Thompson G, Krucoff M, Saito S Harmonization by Doing Program Working Group. Global cardiovascular device innovation: Japan-USA synergies: Harmonization by Doing (HBD) program, a consortium of regulatory agencies, medical device industry, and academic institutions. Circ J. 2013;77:1714–1718.
    1. Guidance for industry non-inferiority clinical trials. Silver Spring (MD): Center for drug evaluation and research and Rockville (MD): Center for biologics evaluation and research, US Food and Drug Administration; 2010. Available at downloads/Drugs/Guidance Compliance Regulatory Information/Guidances/UCM202140.pdf.

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