Hybrid Sirolimus-eluting Versus Everolimus-eluting Stents for Total Coronary Occlusions

NCT01516723 | Unknown Phase 3 DMC

• 1 other identifier: RDC-2011-02
• Study Type: interventional
• Target: 330
• Locations: 2 countries
• Sites: 4

Brief Summary

Percutaneous recanalization of total coronary occlusions (TCO) was historically hampered by high rates of restenosis and reocclusion. In the PRISON II and III trial we showed landmark reduction in restenosis with sirolimus-eluting stents (Cypher, Cordis Corporation) compared to conventional bare metal stents in TCO. In the PRISON III trial, we observed similar favourable results with second-generation zotarolimus-eluting stent (Resolute, Medtronic Inc.). Another drugs-eluting stent mounted with everolimus (Xience Prime, Abbott) also demonstrated favourable results in TCO. Recently, drug-eluting stents (DES) with bioresorbable polymer coatings were developed, to address safety concerns regarding the observation of very late stent thrombosis, due to hypersensitivity reactions, and chronic inflammation, on the durable polymer coating of DES. However, none of these DES with bioresorbable polymers were evaluated in patients with TCO. The PRISON IV trial is a prospective, randomized, single-blinded, multi-center trial, designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (ORSIRO, Biotronik Inc.) compared to everolimus-eluting stents with durable polymers (Xience Prime, Abbott) in patients with successfully recanalized TCOs.

Conditions

Coronary Artery Disease; Coronary Disease; Coronary Stenosis

Keywords

drug-eluting stent; chronic total occlusion; hybrid sirolimus-eluting stent; everolimus-eluting stent

Outcome Measures

Primary Outcomes (1)

• In-segment late luminal loss at 9 months as assessed by an independent angiographic core lab.

  9 month

Secondary Outcomes (8)

• In-stent late luminal loss

  9 month

• In-stent and in-segment binary restenosis rate

  9 month

• In-stent and in-segment minimal lumen diameter

  9 month

• Percentage diameter stenosis

  9 month

• A composite of major adverse cardiac events (MACE: death, myocardial infarction and clinically driven target lesion revascularization)

  9 month

Study Arms (2)

Hybrid sirolimus-eluting stents

EXPERIMENTAL

ORSIRO, Biotronik Inc.

Device: Hybrid sirolimus- and everolimus-eluting stents (ORSIRO, XIENCE PRIME)

Everolimus-eluting stents

ACTIVE COMPARATOR

XIENCE PRIME, Abbott

Device: Hybrid sirolimus- and everolimus-eluting stents (ORSIRO, XIENCE PRIME)

Interventions

Hybrid sirolimus- and everolimus-eluting stents (ORSIRO, XIENCE PRIME) DEVICE

Recanalization of totally occluded coronary arteries

Also known as: Hybrid sirolimus-eluting stents (ORSIRO, Biotronik), Everolimus-eluting stents (XIENCE PRIME, Abbott)

Everolimus-eluting stents; Hybrid sirolimus-eluting stents

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• the estimated duration of the occlusion is at least 4 weeks.
• signs of ischemia related to the occluded coronary artery.
• successful recanalization of the occluded artery is achieved.
• reference diameter is \> 2.5 mm.
• written informed consent obtained.

You may not qualify if:

• primary or rescue PCI for acute myocardial infarction
• the lesion could not be crossed.
• lesions with complex anatomy making successful stent deployment unlikely.
• the guide wire is not in the true lumen distal to the occlusion.
• Sirolimus or zotarolimus allergy
• venous or arterial bypass grafts
• pregnant or nursing women.
• participation in an other trial.
• factors making long-term follow-up difficult or unlikely.
• life expectancy \< 1 year.
• contraindications for ASA or Clopidogrel or heparin.
• use of coumadins that could not be stopped before the procedure.

Sponsors & Collaborators

• R&D Cardiologie: lead
• Biotronik SE & Co. KG: collaborator

Study Sites (4)

AZ Middelheim

Antwerp, Antwerpen, 2020, Belgium

Location

AMC

Amsterdam, Amsterdam, 1105AZ, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Eindhoven, 5602ZA, Netherlands

Location

St Antonius Hospital

Nieuwegein, 3435CM, Netherlands

Location

Related Publications (16)

• Rahel BM, Suttorp MJ, Laarman GJ, Kiemeneij F, Bal ET, Rensing BJ, Ernst SM, ten Berg JM, Kelder JC, Plokker HW. Primary stenting of occluded native coronary arteries: final results of the Primary Stenting of Occluded Native Coronary Arteries (PRISON) study. Am Heart J. 2004 May;147(5):e22. doi: 10.1016/j.ahj.2003.11.023.

  PMID: 15131557 BACKGROUND

• Suttorp MJ, Mast EG, Plokker HW, Kelder JC, Ernst SM, Bal ET. Primary coronary stenting after successful balloon angioplasty of chronic total occlusions: a single-center experience. Am Heart J. 1998 Feb;135(2 Pt 1):318-22. doi: 10.1016/s0002-8703(98)70099-7.

  PMID: 9489982 BACKGROUND

• 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 Oct 2;349(14):1315-23. doi: 10.1056/NEJMoa035071.

  PMID: 14523139 BACKGROUND

• Sirnes PA, Golf S, Myreng Y, Molstad P, Emanuelsson H, Albertsson P, Brekke M, Mangschau A, Endresen K, Kjekshus J. Stenting in Chronic Coronary Occlusion (SICCO): a randomized, controlled trial of adding stent implantation after successful angioplasty. J Am Coll Cardiol. 1996 Nov 15;28(6):1444-51. doi: 10.1016/s0735-1097(96)00349-x.

  PMID: 8917256 BACKGROUND

• Suttorp MJ, Laarman GJ, Rahel BM, Kelder JC, Bosschaert MA, Kiemeneij F, Ten Berg JM, Bal ET, Rensing BJ, Eefting FD, Mast EG. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions. Circulation. 2006 Aug 29;114(9):921-8. doi: 10.1161/CIRCULATIONAHA.106.613588. Epub 2006 Aug 14.

  PMID: 16908768 BACKGROUND

• Kandzari DE, Leon MB, Popma JJ, Fitzgerald PJ, O'Shaughnessy C, Ball MW, Turco M, Applegate RJ, Gurbel PA, Midei MG, Badre SS, Mauri L, Thompson KP, LeNarz LA, Kuntz RE; ENDEAVOR III Investigators. Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial. J Am Coll Cardiol. 2006 Dec 19;48(12):2440-7. doi: 10.1016/j.jacc.2006.08.035. Epub 2006 Nov 28.

  PMID: 17174180 BACKGROUND

• Wohrle J, Rottbauer W, Imhof A. Everolimus-eluting stents for treatment of chronic total coronary occlusions. Clin Res Cardiol. 2012 Jan;101(1):23-8. doi: 10.1007/s00392-011-0359-3. Epub 2011 Sep 22.

  PMID: 21938564 BACKGROUND

• Rahel BM, Laarman GJ, Kelder JC, Ten Berg JM, Suttorp MJ. Three-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomized comparison of bare-metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (Primary Stenting of Totally Occluded Native Coronary Arteries [PRISON] II study). Am Heart J. 2009 Jan;157(1):149-55. doi: 10.1016/j.ahj.2008.08.025. Epub 2008 Nov 6.

  PMID: 19081412 BACKGROUND

• Van den Branden BJ, Rahel BM, Laarman GJ, Slagboom T, Kelder JC, Ten Berg JM, Suttorp MJ. Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study). EuroIntervention. 2012 Feb;7(10):1189-96. doi: 10.4244/EIJV7I10A190.

  PMID: 22030323 BACKGROUND

• 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 Feb 17;109(6):701-5. doi: 10.1161/01.CIR.0000116202.41966.D4. Epub 2004 Jan 26.

  PMID: 14744976 BACKGROUND

• Virmani R, Liistro F, Stankovic G, Di Mario C, Montorfano M, Farb A, Kolodgie FD, Colombo A. Mechanism of late in-stent restenosis after implantation of a paclitaxel derivate-eluting polymer stent system in humans. Circulation. 2002 Nov 19;106(21):2649-51. doi: 10.1161/01.cir.0000041632.02514.14.

  PMID: 12438288 BACKGROUND

• Cook S, Ladich E, Nakazawa G, Eshtehardi P, Neidhart M, Vogel R, Togni M, Wenaweser P, Billinger M, Seiler C, Gay S, Meier B, Pichler WJ, Juni P, Virmani R, Windecker S. Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation. 2009 Aug 4;120(5):391-9. doi: 10.1161/CIRCULATIONAHA.109.854398. Epub 2009 Jul 20.

  PMID: 19620501 BACKGROUND

• Stefanini GG, Kalesan B, Serruys PW, Heg D, 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, van Es GA, Meier B, Windecker S, Juni P. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. 2011 Dec 3;378(9807):1940-8. doi: 10.1016/S0140-6736(11)61672-3. Epub 2011 Nov 8.

  PMID: 22075451 BACKGROUND

• Ughi GJ, Adriaenssens T, Onsea K, Kayaert P, Dubois C, Sinnaeve P, Coosemans M, Desmet W, D'hooge J. Automatic segmentation of in-vivo intra-coronary optical coherence tomography images to assess stent strut apposition and coverage. Int J Cardiovasc Imaging. 2012 Feb;28(2):229-41. doi: 10.1007/s10554-011-9824-3. Epub 2011 Feb 24.

  PMID: 21347593 BACKGROUND

• Moreno R, Garcia E, Teles RC, Almeida MS, Carvalho HC, Sabate M, Martin-Reyes R, Rumoroso JR, Galeote G, Goicolea FJ, Moreu J, Mainar V, Mauri J, Ferreira R, Valdes M, Perez de Prado A, Martin-Yuste V, Jimenez-Valero S, Sanchez-Recalde A, Calvo L, Lopez de Sa E, Macaya C, Lopez-Sendon JL. A randomised comparison between everolimus-eluting stent and sirolimus-eluting stent in chronic coronary total occlusions. Rationale and design of the CIBELES (non-acute Coronary occlusion treated by EveroLimus-Eluting Stent) trial. EuroIntervention. 2010 May;6(1):112-6.

  PMID: 20542806 BACKGROUND

• Teeuwen K, Adriaenssens T, Van den Branden BJ, Henriques JP, Van der Schaaf RJ, Koolen JJ, Vermeersch PH, Bosschaert MA, Tijssen JG, Suttorp MJ. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study. Trials. 2012 Dec 15;13:240. doi: 10.1186/1745-6215-13-240.

  PMID: 23241457 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Coronary Disease; Coronary Stenosis

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Maarten J. Suttorp, MD, PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: January 25, 2012
• Study Start: February 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2020
• Last Updated: March 28, 2017

Record last verified: 2017-03

Locations

BE (1); NL (3)