Sirolimus-eluting vs Zotarolimus-eluting Stents for Chronic Total Coronary Occlusions

Coronary Artery Disease Clinical Trial

Official title:

A Randomized Comparison of Sirolimus-eluting Stent Implantation With Zotarolimus-eluting Stent Implantation for the Treatment of Chronic Total Coronary Occlusions. The PRISON III Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00428454
• Other study ID #: RDC-2006-02
• Status: Completed
• Phase: Phase 3
• First received: January 29, 2007
• Last updated: June 3, 2015
• Start date: January 2007
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: R&D Cardiologie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Primary intracoronary stent placement after successfully crossing chronic total coronary occlusions (CTO) decreases the high restenosis rate at long-term follow-up compared with conventional balloon angioplasty. Several studies have shown the efficacy of sirolimus-eluting stents in selected groups of patients. In the PRISON II study we demonstrated that sirolimus-eluting stents were superior to bare metal stents in CTO. In this prospective randomized trial, sirolimus-stent implantation will be compared with zotarolimus-eluting stent implantation for the treatment of chronic total coronary occlusions. A total of 300 patients will be clinically followed up for 1, 6, 12 months, 2, 3, 4, 5 year with angiographic follow-up at 8 months. Quantitative coronary analysis will be performed by an independent core laboratory. The primary end point is in-segment late luminal loss at 8 month angiographic follow-up.

Description:

Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) was traditionally limited by high restenosis rates. Coronary stenting using bare metal stents significantly decreases restenosis in CTO compared to balloon angioplasty alone, but restenosis rates still reach 32-55%. In 200 patients with CTO, randomized in the PRISON I study we demonstrated a restenosis rate of 22% after bare metal stent (BMS) implantation as compared with 33% after conventional balloon angioplasty. During the past few years, sirolimus (rapamycin), a cytostatic macrocyclic lactone with anti-inflammatory and antiproliferative properties, delivered from a polymer-encapsulated stent was shown to almost eliminate the risk of restenosis in selected groups of patients. The drug zotarolimus (ABT-578), a sirolimus analogue, is designed to inhibit the cellular process that leads to restenosis. In the PRISON II study we have randomized 200 patients with CTO to either BMS implantation or sirolimus-eluting stent implantation and we demonstrated a reduction of in-stent binary restenosis from 36% to 7% and in-segment binary restenosis rates from 41% to 11% in favour of the sirolimus eluting stent. However, no data are available on direct comparison of the clinical efficacy, safety, and angiographic outcome of particular drug-eluting stents in patients with CTO and there may be differences between various drug-eluting stents. The PRISON III study is designed to address this issue and provide information about two different drug-eluting stents. It is a prospective randomized, single blinded trial comparing the relative safety, clinical efficacy and angiographic outcomes of sirolimus and zotarolimus-eluting stents in patients undergoing successful recanalization of CTO.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 301
• Est. completion date: June 2015
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA

• the estimated duration of the occlusion is at least 2 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.

EXCLUSION CRITERIA

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Occlusion
• Coronary Stenosis
• Myocardial Ischemia

Intervention

Device:
• sirolimus-eluting stent, zotarolimus-eluting stent
PCI in chronically occluded coronary artery

Locations

Country	Name	City	State
Belgium	AZ Middelheim	Antwerpen
Netherlands	AMC	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	St Antonius Hospital	Nieuwegein

Sponsors (2)

Lead Sponsor	Collaborator
R&D Cardiologie	Cordis Corporation

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (9)

Fajadet J, Wijns W, Laarman GJ, Kuck KH, Ormiston J, Münzel T, Popma JJ, Fitzgerald PJ, Bonan R, Kuntz RE; ENDEAVOR II Investigators. Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation. 2006 Aug 22;114(8):798-806. Epub 2006 Aug 14. — View Citation

Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med. 1994 Aug 25;331(8):496-501. — View Citation

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. Epub 2006 Nov 28. — View Citation

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. — View Citation

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. — View Citation

Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994 Aug 25;331(8):489-95. — View Citation

Sirnes PA, Golf S, Myreng Y, Mølstad 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. — View Citation

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. Epub 2006 Aug 14. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-segment late luminal loss at 8 months as assessed by an independent angiographic core lab.		8 month	No
Secondary	In-stent late luminal loss		8 month	No
Secondary	In-stent and in-segment binary restenosis rate		8 month	No
Secondary	In-stent and in-segment MLD		8 month	No
Secondary	Percentage diameter stenosis		8 month	No
Secondary	A composite of major adverse cardiac events (MACE: death, myocardial infarction and clinically driven target lesion revascularization)		8 month	Yes
Secondary	Stent thrombosis (acute, <1day; subacute, 1 to 30 days; and late, >30 days)		30 days	Yes
Secondary	Target vessel failure up to 5 year of clinical follow-up.		5 years	Yes