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

Coronary Artery Disease Clinical Trial

— PRISON-IV  

Official title:

Hybrid Sirolimus-eluting Stent With Bioresorbable Polymer Versus Everolimus-eluting Stent With Durable Polymer for Total Coronary Occlusions in Native Coronary Arteries (PRISON-IV)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01516723
• Other study ID #: RDC-2011-02
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 15, 2011
• Last updated: March 27, 2017
• Start date: February 2012
• Est. completion date: May 2020

Study information

• Verified date: March 2017
• Source: R&D Cardiologie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

A total of 330 patients are randomized to either hybrid sirolimus-eluting stent or everolimus-eluting stent after successful recanalization of TCO. Clinical follow-up at 1, 6, 12 months, 2, 3, 4, 5 year with angiographic follow-up at 9 months. In 60 patients a optical coherence tomography is performed during the 9 months follow-up angiography. Quantitative coronary and optical coherence tomography analysis is performed by two independent core laboratory. The primary end point is in-segment late luminal loss at 9 month angiographic follow-up. Secondary angiographic end points include the following; in-stent luminal loss, acute recoil, acute gain, net luminal gain, late loss index, minimal lumen diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9 months angiographic follow-up. Secondary clinical endpoints include a composite of major adverse cardiac events (death, MI and clinically driven target lesion revascularization); clinically driven target vessel revascularisation (TVR), target vessel failure (cardiac death, MI, clinically driven TVR) and stent thrombosis up to 5 year clinical follow-up. Tertiary optical coherence tomography end points at 9 months follow-up are the following: Percentage of uncovered stent struts, percentage of malapposed stent struts, tissue strut thickness, absolute and percentage of intimal hyperplasia.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 330
• Est. completion date: May 2020
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• 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.

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.

Related Conditions & MeSH terms

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

Intervention

Device:
• Hybrid sirolimus- and everolimus-eluting stents (ORSIRO, XIENCE PRIME)
Recanalization of totally occluded coronary arteries

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
R&D Cardiologie	Biotronik SE & Co. KG

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (15)

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, Jüni 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. — 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

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. doi: 10.4244/. — 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, 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. — 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

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

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, Jüni 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. — 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

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. — View Citation

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. — View Citation

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. Epub 2004 Jan 26. — View Citation

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. — View Citation

Wöhrle 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-segment late luminal loss at 9 months as assessed by an independent angiographic core lab.		9 month
Secondary	In-stent late luminal loss		9 month
Secondary	In-stent and in-segment binary restenosis rate		9 month
Secondary	In-stent and in-segment minimal lumen diameter		9 month
Secondary	Percentage diameter stenosis		9 month
Secondary	A composite of major adverse cardiac events (MACE: death, myocardial infarction and clinically driven target lesion revascularization)		9 month
Secondary	Stent thrombosis (acute, <1day; subacute, 1 to 30 days; and late, >30 days)		30 days
Secondary	Target vessel failure (cardiac death, MI, clinically driven target vessel revascularisation) up to 5 year of clinical follow-up.		5 years
Secondary	% of uncovered stent struts, % of malapposed stent struts, tissue strut thickness (µm), absolute volume (mm³) and % of intimal hyperplasia	Assessed by optical coherence tomography	9 month