Sirolimus-eluting Stents With Biodegradable Polymer Versus an Everolimus-eluting Stents

Coronary Artery Disease Clinical Trial

Official title:

A Randomized Comparison of a Sirolimus-eluting Stent With Biodegradable Polymer Versus an Everolimus-eluting Stent With a Durable Polymer for Percutaneous Coronary Revascularization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01443104
• Other study ID #: 065/11
• Status: Completed
• Phase: N/A
• Start date: February 2012
• Est. completion date: June 2018

Study information

• Verified date: October 2018
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Coronary artery stents have improved the safety and efficacy of percutaneous coronary intervention for coronary artery disease. Drug-eluting stents have been shown to decrease neointimal hyperplasia and to reduce the rate of restenosis and target-lesion revascularization as compared to bare-metal stents. Drug-eluting stents consist of a metallic platform and a therapeutic substance that is usually released from a polymer matrix. A previous study utilizing a bioresorbable polymer has demonstrated a favorable safety and efficacy profile in a large-scale clinical trial as compared to a first-generation druf-eluting stent (LEADERS trial).

The objective of the study is to compare the safety and efficacy of a sirolimus-eluting stent with a biodegradable polymer with an everolimus-eluting stent with a durable polymer in a prospective multicenter randomized controlled non-inferiority trial in patients undergoing percutaneous coronary intervention in routine clinical practice.

Description:

Background

Coronary artery stents have improved the safety and efficacy of percutaneous coronary interventions compared with balloon angioplasty alone (New Engl J Med 1994; 331:489-495). Notwithstanding, restenosis is still encountered in 20 to 30% of lesions after implantation of bare metal stents (JAMA 2000; 284:1828-36) and may require repeat revascularization procedures with a negative impact on quality of life and health care expenditures. Drug-eluting stents with local, controlled release of therapeutic agents have addressed this problem successfully (Circulation 2003; 107:3003-7). Current drug-eluting stents consist of a metallic stent platform and a therapeutic agent, which is either directly immobilized on the stent surface or released from a polymer matrix. Polymers currently utilized for drug-eluting stents are either biodegradable or non-biodegradable. While biodegradable polymers are released together with the drug and dissolve after a certain period of time, non-biodegradable polymers reside permanently on the stent surface.

First-generation drug-eluting stents utilized sirolimus and paclitaxel for prevention of restenosis. Both drugs are highly lipophilic and show rapid and strong uptake in arterial wall tissue. In addition, Sirolimus (Circulation 2001; 104:852-5) and paclitaxel (Circulation 1997; 96:636-45) have been shown to reduce smooth muscle cell proliferation and neointimal hyperplasia, the principal cause of restenosis after coronary stenting in experimental models. A polymer-encapsulated stent releasing Sirolimus has been compared with the respective bare metal stent in several randomized clinical trials, demonstrating a consistent reduction in angiographic and clinical restenosis (N Engl J Med 2002; 346:1773-80). Similarly, a polymer-based, paclitaxel-eluting stent consistently reduced restenosis and the need for repeated revascularization procedures compared with the respective bare metal stent (N Engl J Med 2004; 350:221-31). A meta-analysis of drug-eluting stent trials confirmed the reduction in restenosis and repeat revascularization procedures for polymer-based, drug-eluting stents (Lancet 2004; 364:583-91). Moreover, the rates of death and myocardial infarction were comparable to those with bare metal stents, attesting to the safety of these devices, which have been approved by the US Food and Drug Administration.

Newer generation drug-eluting stents with durable polymer coating utilize Limus analogues such as everolimus, zotarolimus or novolimus. Everolimus-eluting stents have been compared to first-generation drug-eluting stents in several randomized clinical trials. A pooled analysis of the four largest randomized trials to date comparing everolimus-eluting stents with paclitaxel-eluting stents demonstrated a lower rate of MACE (4.4% versus 7.6%), myocardial infarction (2.1% vs. 4.0%, p<0.001), ischemic TLR (2.3% vs. 4.7%, p<0.001), and definite stent thrombosis (0.4% vs. 1.2%, p<0.001) in favor of EES, whereas there was no difference with regard to overall and cardiac mortality (Stone GW. The XIENCE V - PROMUS Everolimus-Eluting Stent: New Insights from the SPIRIT/COMPARE Meta-analysis and other randomized trials. Presentation at Transcatheter Cardiovascular Therapeutics, September 22nd 2010). At the same time several trials comparing everolimus-eluting stents with sirolimus-eluting stents reported favorable performance of everolimus-eluting stents. In a randomized trial enrolling 2'774 patients everolimus-eluting stents were non-inferior compared with sirolimus-eluting stents at nine months with regard to MACE (4.9% vs. 5.2%, HR 0.94, 0.67-1.31) and TLR (1.4% vs. 1.7%, HR 0.87, 0.48-1.58) (N Engl J Med 2010;362(28):1663-74). Likewise, event rates at two years were similar for everolimus-eluting stents and sirolimus-eluting stents (3.7% versus 4.3%, p=0.85) in a randomized controlled trial comparing EES, SES, and BMS in large vessels (stent diameter >3.0 mm), whereas TVR was lower with both EES (3.7%) and SES (4.3%) as compared with bare-metal stents (10.3%, P=0.005 vs SES, P=0.002 vs EES) (N Engl J Med 2010;363(24):2310-9). A propensity-score matched comparison of EES and SES reported lower event rates of myocardial infarction (3.3% versus 5.0%, HR 0.62, 95% CI 0.42-0.92, P=0.017) in part due to a lower risk of stent thrombosis (definite or probable 2.5% versus 4.0%, HR 0.64, 95% CI 0.41-0.98, P=0.041), as well as a lower rate of target vessel revascularization (7.0% versus 9.6%, HR 0.75, 95% CI 0.57-0.99, P=0.039) for EES at three years while mortality was similar (Windecker S. Long-term comparison of Everolimus-eluting and Sirolimus-eluting Stents for coronary revascularization 1 (LESSON1) study. Presentation at the European Society of Cardiology meeting, Stockholm, Sweden, 31st August 2010. 2010).

A previous study utilizing a bioresorbable polymer has demonstrated a favorable safety and efficacy profile in a large-scale clinical trial as compared to a first-generation drug-eluting stent. Among 1,707 patients randomized to either a biolimus-eluting stent with a bioresorbable polymer or a sirolimus-eluting stent with a durable polymer no significant differences with regard to the primary endpoint of cardiac death, myocardial infarction or target-vessel revascularization were observed (9.2% versus 10.5%, HR 0.88, 95% CI 0.64-1.19;: p=0.39)(Lancet 2008;372:1163-73.)

Objective

The objective of the study is to compare the safety and efficacy of a sirolimus-eluting stent with a biodegradable polymer with an everolimus-eluting stent with a durable polymer in a prospective multicenter randomized controlled non-inferiority trial in patients undergoing percutaneous coronary intervention in routine clinical practice.

Methods

Design: Prospective, multi-center, randomized, non-inferiority trial. Patients will be randomized in a single-blind fashion (1:1 randomization) to either the Orsiro® Stent system (Sirolimus-eluting stent with a biodegradable polymer) with the Xience PRIME® stent system (Everolimus-eluting stent with a durable polymer).

Primary endpoint: Target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target-lesion revascularization (TLR).

Inclusion Criteria: "Real world, all comer" patients with symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes including NSTE-ACS and STE-ACS, and presence of one or more coronary artery stenoses >50% in a native coronary artery or a saphenous bypass graft which can be treated with a stent ranging in diameter from 2.25 to 4.0 mm and can be covered with one or multiple stents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2119
• Est. completion date: June 2018
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years

• Symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes including NSTE-ACS and STE-ACS

• Presence of one or more coronary artery stenoses >50% in a native coronary artery or a saphenous bypass graft which can be treated with a stent ranging in diameter from 2.25 to 4.0 mm and can be covered with one or multiple stents

• No limitation on the number of treated lesions, and vessels, and lesion length

Exclusion Criteria

• Pregnancy

• Known intolerance to aspirin, clopidogrel, heparin, stainless steel, Sirolimus, Everolimus or contrast material

• Inability to provide informed consent

• Currently participating in another trial before reaching first endpoint

• Planned surgery within 6 months of PCI unless dual antiplatelet therapy is maintained throughout the peri-surgical period

Related Conditions & MeSH terms

• Angina Pectoris
• Coronary Artery Disease
• Coronary Disease
• Infarction
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Device:
• Sirolimus-eluting stent with a bioresorbable polymer (Orsiro)
Percutaneous coronary intervention with implantation of a sirolimus-eluting stent with a bioresorbable polymer for coronary artery disease
• Everolimus-eluting stent with a durable polymer
Percutaneous coronary intervention with implantation of an everolimus-eluting stent with a durable polymer for coronary artery disease

Locations

Country	Name	City	State
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Universitätsklinik Basel	Basel
Switzerland	Department of Cardiology, Bern University Hospital	Bern
Switzerland	HFR Freiburg	Freiburg
Switzerland	Hôpitaux Universitaires de Genève	Genève
Switzerland	Service de cardiologie CHUV	Lausanne
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Stadtspital Triemli	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Biotronik AG, University of Bern

Country where clinical trial is conducted

Switzerland, 

References & Publications (5)

Franzone A, Pilgrim T, Heg D, Roffi M, Tüller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Räber L, Stortecky S, Wenaweser P, Jüni P, Windecker S. Clinical outcomes according to diabetic status in patients treated with biodegra — View Citation

Pilgrim T, Heg D, Roffi M, Tüller D, Muller O, Vuilliomenet A, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Fahrni T, Moschovitis A, Noble S, Eberli FR, Wenaweser P, Jüni P, Windecker S. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus — View Citation

Pilgrim T, Piccolo R, Heg D, Roffi M, Tüller D, Muller O, Moarof I, Siontis GCM, Cook S, Weilenmann D, Kaiser C, Cuculi F, Hunziker L, Eberli FR, Jüni P, Windecker S. Ultrathin-strut, biodegradable-polymer, sirolimus-eluting stents versus thin-strut, dura — View Citation

Pilgrim T, Piccolo R, Heg D, Roffi M, Tüller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Khattab AA, Taniwaki M, Rigamonti F, Nietlispach F, Blöchlinger S, Wenaweser P, Jüni P, Windecker S. Biodegradable polymer sirolimus-elut — View Citation

Zbinden R, Piccolo R, Heg D, Roffi M, Kurz DJ, Muller O, Vuilliomenet A, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Franzone A, Eberli F, Jüni P, Windecker S, Pilgrim T. Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Target lesion failure (TLF), defined as the composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) and emergent coronary artery bypass grafting (CABG)		12 months
Secondary	Number of patients with target lesion revascularization (TLR)		30 days
Secondary	Number of patients with target lesion revascularization (TLR)		1 year
Secondary	Number of patients with target lesion revascularization (TLR)		2 years
Secondary	Number of patients with target lesion revascularization (TLR)		5 years
Secondary	Clinically indicated and not clinically indicated target vessel revascularization (TVR)		30 days
Secondary	Clinically indicated and not clinically indicated target vessel revascularization (TVR)		1 year
Secondary	Clinically indicated and not clinically indicated target vessel revascularization (TVR)		2 years
Secondary	Clinically indicated and not clinically indicated target vessel revascularization (TVR)		5 years
Secondary	TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)		30 days
Secondary	TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)		2 years
Secondary	TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)		5 years
Secondary	All-cause mortality		30 days
Secondary	All-cause mortality		1 year
Secondary	All-cause mortality		2 years
Secondary	All-cause mortality		5 years
Secondary	Definite stent thrombosis		30 days
Secondary	Definite stent thrombosis		1 year
Secondary	Definite stent thrombosis		2 years
Secondary	Definite stent thrombosis		3 years
Secondary	Definite stent thrombosis		5 years
Secondary	Myocardial infarction (Q-wave and NQWMI)		30 days
Secondary	Myocardial infarction (Q-wave and NQWMI)		1 year
Secondary	Myocardial infarction (Q-wave and NQWMI)		2 years
Secondary	Myocardial infarction (Q-wave and NQWMI)		3 years
Secondary	Myocardial infarction (Q-wave and NQWMI)		5 years