Coronary Artery DiseaseNCT01443104
Sirolimus-eluting Stents With Biodegradable Polymer Versus an Everolimus-eluting Stents
A study testing Sirolimus-eluting stent with a bioresorbable polymer (Orsiro) and Everolimus-eluting stent with a durable polymer in people with Coronary Artery Disease and Angina Pectoris, run by Insel Gruppe AG, University Hospital Bern at 9 sites in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Angina Pectoris, Myocardial Infarction
- What is being tested?
- Sirolimus-eluting stent with a bioresorbable polymer (Orsiro) and Everolimus-eluting stent with a durable polymer
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,119 participants
- Where
- 9 sitesSwitzerland
- Study dates
- Feb 2012to Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Switzerland9 sites
Kantonsspital Aarau
Aarau, 5000
Universitätsklinik Basel
Basel, 4031
Department of Cardiology, Bern University Hospital
Bern, 3010
HFR Freiburg
Fribourg, 1708
Hôpitaux Universitaires de Genève
Geneva, 1211
Service de cardiologie CHUV
Lausanne, 1010
Luzerner Kantonsspital
Lucerne, 6004
Kantonsspital St. Gallen
Sankt Gallen, 9007
Stadtspital Triemli
Zurich, 8055
About this study
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
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.
Read the detailed 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.
- Being tested
- Sirolimus-eluting stent with a bioresorbable polymer (Orsiro), Everolimus-eluting stent with a durable polymer
- Keywords
- coronary artery disease, drug-eluting stents, polymers
- Medical subject headings
- Coronary Artery Disease, Angina Pectoris, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus-eluting stent with a bioresorbable polymer (Orsiro)Device
Percutaneous coronary intervention with implantation of a sirolimus-eluting stent with a bioresorbable polymer for coronary artery disease
Everolimus-eluting stent with a durable polymerDevice
Percutaneous coronary intervention with implantation of an everolimus-eluting stent with a durable polymer for coronary artery disease
| Study group | Role | What they receive |
|---|---|---|
| Orsiro Stent | Active comparator | Sirolimus-eluting Stent with a Biodegradable Polymer Receives: Device: Sirolimus-eluting stent with a bioresorbable polymer (Orsiro) |
| Xience Prime Stent | Active comparator | Everolimus-eluting Stent with a Durable Polymer Receives: Device: Everolimus-eluting stent with a durable polymer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 12 months
Secondary outcomes (25)
Number of patients with target lesion revascularization (TLR)
Measured: 30 days
Number of patients with target lesion revascularization (TLR)
Measured: 1 year
Number of patients with target lesion revascularization (TLR)
Measured: 2 years
Number of patients with target lesion revascularization (TLR)
Measured: 5 years
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Measured: 30 days
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Measured: 1 year
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Measured: 2 years
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Measured: 5 years
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Measured: 30 days
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Measured: 2 years
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Measured: 5 years
All-cause mortality
Measured: 30 days
All-cause mortality
Measured: 1 year
All-cause mortality
Measured: 2 years
All-cause mortality
Measured: 5 years
Definite stent thrombosis
Measured: 30 days
Definite stent thrombosis
Measured: 1 year
Definite stent thrombosis
Measured: 2 years
Definite stent thrombosis
Measured: 3 years
Definite stent thrombosis
Measured: 5 years
Myocardial infarction (Q-wave and NQWMI)
Measured: 30 days
Myocardial infarction (Q-wave and NQWMI)
Measured: 1 year
Myocardial infarction (Q-wave and NQWMI)
Measured: 2 years
Myocardial infarction (Q-wave and NQWMI)
Measured: 3 years
Myocardial infarction (Q-wave and NQWMI)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2011 (estimated)
- Study startFeb 2012
- Primary completionJun 2014
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Biotronik AG, University of Bern
- Responsible party
- Sponsor
- Investigators
- Stephan Windecker, Principal investigator, Department of Cardiology, Bern University Hospital, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01443104
- Sponsor's protocol ID
- 065/11
- Status last verified
- Oct 2018
- First submitted
- 21 Sep 2011
- Last updated
- 18 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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, Juni P, Windecker S, Pilgrim T. Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial. J Am Heart Assoc. 2016 Mar 15;5(3):e003255. doi: 10.1161/JAHA.116.003255.
PubMed 26979080Franzone A, Pilgrim T, Heg D, Roffi M, Tuller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Raber L, Stortecky S, Wenaweser P, Juni P, Windecker S. Clinical outcomes according to diabetic status in patients treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: prespecified subgroup analysis of the BIOSCIENCE trial. Circ Cardiovasc Interv. 2015 Jun;8(6):e002319. doi: 10.1161/CIRCINTERVENTIONS.114.002319.
PubMed 26043895Pilgrim T, Piccolo R, Heg D, Roffi M, Tuller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Khattab AA, Taniwaki M, Rigamonti F, Nietlispach F, Blochlinger S, Wenaweser P, Juni P, Windecker S. Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction. EuroIntervention. 2016 Dec 10;12(11):e1343-e1354. doi: 10.4244/EIJY15M12_09.
PubMed 26690319Pilgrim T, Heg D, Roffi M, Tuller D, Muller O, Vuilliomenet A, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Fahrni T, Moschovitis A, Noble S, Eberli FR, Wenaweser P, Juni P, Windecker S. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial. Lancet. 2014 Dec 13;384(9960):2111-22. doi: 10.1016/S0140-6736(14)61038-2. Epub 2014 Sep 1.
PubMed 25189359Pilgrim T, Piccolo R, Heg D, Roffi M, Tuller D, Muller O, Moarof I, Siontis GCM, Cook S, Weilenmann D, Kaiser C, Cuculi F, Hunziker L, Eberli FR, Juni P, Windecker S. Ultrathin-strut, biodegradable-polymer, sirolimus-eluting stents versus thin-strut, durable-polymer, everolimus-eluting stents for percutaneous coronary revascularisation: 5-year outcomes of the BIOSCIENCE randomised trial. Lancet. 2018 Sep 1;392(10149):737-746. doi: 10.1016/S0140-6736(18)31715-X. Epub 2018 Aug 28.
PubMed 30170848Haner JD, Rohla M, Losdat S, Iglesias JF, Muller O, Eeckhout E, Kurz D, Weilenmann D, Kaiser C, Tapponnier M, Roffi M, Heg D, Windecker S, Pilgrim T. Ultrathin-strut vs thin-strut drug-eluting stents for multi and single-stent lesions: A lesion-level subgroup analysis of 2 randomized trials. Am Heart J. 2023 Sep;263:73-84. doi: 10.1016/j.ahj.2023.05.004. Epub 2023 May 14.
PubMed 37192697Iglesias JF, Muller O, Losdat S, Roffi M, Kurz DJ, Weilenmann D, Kaiser C, Heg D, Windecker S, Pilgrim T. Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial. Catheter Cardiovasc Interv. 2023 Mar;101(4):687-700. doi: 10.1002/ccd.30600. Epub 2023 Feb 19.
PubMed 36807456Iglesias JF, Heg D, Roffi M, Degrauwe S, Tuller D, Muller O, Brinkert M, Cook S, Weilenmann D, Kaiser C, Cuculi F, Valgimigli M, Juni P, Windecker S, Pilgrim T. Five-Year Outcomes With Biodegradable-Polymer Sirolimus-Eluting Stents Versus Durable-Polymer Everolimus-Eluting Stents in Patients With Acute Coronary Syndrome: A Subgroup Analysis of the BIOSCIENCE Trial. Cardiovasc Revasc Med. 2022 Jan;34:3-10. doi: 10.1016/j.carrev.2021.02.008. Epub 2021 Feb 25.
PubMed 33653633Iglesias JF, Heg D, Roffi M, Tuller D, Lanz J, Rigamonti F, Muller O, Moarof I, Cook S, Weilenmann D, Kaiser C, Cuculi F, Valgimigli M, Juni P, Windecker S, Pilgrim T. Five-Year Outcomes in Patients With Diabetes Mellitus Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents. J Am Heart Assoc. 2019 Nov 19;8(22):e013607. doi: 10.1161/JAHA.119.013607. Epub 2019 Nov 7.
PubMed 31696762Iglesias JF, Heg D, Roffi M, Tuller D, Noble S, Muller O, Moarof I, Cook S, Weilenmann D, Kaiser C, Cuculi F, Haner J, Juni P, Windecker S, Pilgrim T. Long-Term Effect of Ultrathin-Strut Versus Thin-Strut Drug-Eluting Stents in Patients With Small Vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Subgroup Analysis of the BIOSCIENCE Randomized Trial. Circ Cardiovasc Interv. 2019 Aug;12(8):e008024. doi: 10.1161/CIRCINTERVENTIONS.119.008024. Epub 2019 Aug 6.
PubMed 31525083Koskinas KC, Siontis GC, Piccolo R, Franzone A, Haynes A, Rat-Wirtzler J, Silber S, Serruys PW, Pilgrim T, Raber L, Heg D, Juni P, Windecker S. Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients. Circ Cardiovasc Interv. 2016 Feb;9(2):e003255. doi: 10.1161/CIRCINTERVENTIONS.115.003255.
PubMed 26823484Campos CM, Costa F, Garcia-Garcia HM, Bourantas C, Suwannasom P, Valgimigli M, Morel MA, Windecker S, Serruys PW. Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials. Circ Cardiovasc Interv. 2015 Apr;8(4):e002279. doi: 10.1161/CIRCINTERVENTIONS.114.002279.
PubMed 25825008Pilgrim T, Roffi M, Tuller D, Muller O, Vuilliomenet A, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Heg D, Juni P, Windecker S. Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: rationale and design of the BIOSCIENCE trial. Am Heart J. 2014 Sep;168(3):256-61. doi: 10.1016/j.ahj.2014.06.004. Epub 2014 Jun 6.
PubMed 25173535
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01443104
- Acronym / sponsor ID
- 065/11
- Keywords
- coronary artery disease, drug-eluting stents, polymers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,119 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Biotronik AG, University of Bern
- Study start
- Feb 2012 (actual)
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 29 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Orsiro Stent | Active comparator | Device: Sirolimus-eluting stent with a bioresorbable polymer (Orsiro)Sirolimus-eluting Stent with a Biodegradable Polymer |
| Xience Prime Stent | Active comparator | Device: Everolimus-eluting stent with a durable polymerEverolimus-eluting Stent with a Durable Polymer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Device | Orsiro Stent |
| Everolimus-eluting stent with a durable polymerPercutaneous coronary intervention with implantation of an everolimus-eluting stent with a durable polymer for coronary artery disease | Device | Xience Prime Stent |
Primary outcome
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)
Time frame: 12 months
25 secondary outcomes
Number of patients with target lesion revascularization (TLR)
Time frame: 30 days
Number of patients with target lesion revascularization (TLR)
Time frame: 1 year
Number of patients with target lesion revascularization (TLR)
Time frame: 2 years
Number of patients with target lesion revascularization (TLR)
Time frame: 5 years
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Time frame: 30 days
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Time frame: 1 year
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Time frame: 2 years
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
Time frame: 5 years
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Time frame: 30 days
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Time frame: 2 years
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI)
Time frame: 5 years
All-cause mortality
Time frame: 30 days
All-cause mortality
Time frame: 1 year
All-cause mortality
Time frame: 2 years
All-cause mortality
Time frame: 5 years
Definite stent thrombosis
Time frame: 30 days
Definite stent thrombosis
Time frame: 1 year
Definite stent thrombosis
Time frame: 2 years
Definite stent thrombosis
Time frame: 3 years
Definite stent thrombosis
Time frame: 5 years
Myocardial infarction (Q-wave and NQWMI)
Time frame: 30 days
Myocardial infarction (Q-wave and NQWMI)
Time frame: 1 year
Myocardial infarction (Q-wave and NQWMI)
Time frame: 2 years
Myocardial infarction (Q-wave and NQWMI)
Time frame: 3 years
Myocardial infarction (Q-wave and NQWMI)
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2018.
- Results publication: PubMed 26979080Zbinden 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, Juni P, Windecker S, Pilgrim T. Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial. J Am Heart Assoc. 2016 Mar 15;5(3):e003255. doi: 10.1161/JAHA.116.003255.
- Results publication: PubMed 26043895Franzone A, Pilgrim T, Heg D, Roffi M, Tuller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Raber L, Stortecky S, Wenaweser P, Juni P, Windecker S. Clinical outcomes according to diabetic status in patients treated with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents: prespecified subgroup analysis of the BIOSCIENCE trial. Circ Cardiovasc Interv. 2015 Jun;8(6):e002319. doi: 10.1161/CIRCINTERVENTIONS.114.002319.
- Results publication: PubMed 26690319Pilgrim T, Piccolo R, Heg D, Roffi M, Tuller D, Vuilliomenet A, Muller O, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Khattab AA, Taniwaki M, Rigamonti F, Nietlispach F, Blochlinger S, Wenaweser P, Juni P, Windecker S. Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction. EuroIntervention. 2016 Dec 10;12(11):e1343-e1354. doi: 10.4244/EIJY15M12_09.
- Results publication: PubMed 25189359Pilgrim T, Heg D, Roffi M, Tuller D, Muller O, Vuilliomenet A, Cook S, Weilenmann D, Kaiser C, Jamshidi P, Fahrni T, Moschovitis A, Noble S, Eberli FR, Wenaweser P, Juni P, Windecker S. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial. Lancet. 2014 Dec 13;384(9960):2111-22. doi: 10.1016/S0140-6736(14)61038-2. Epub 2014 Sep 1.
- Results publication: PubMed 30170848Pilgrim T, Piccolo R, Heg D, Roffi M, Tuller D, Muller O, Moarof I, Siontis GCM, Cook S, Weilenmann D, Kaiser C, Cuculi F, Hunziker L, Eberli FR, Juni P, Windecker S. Ultrathin-strut, biodegradable-polymer, sirolimus-eluting stents versus thin-strut, durable-polymer, everolimus-eluting stents for percutaneous coronary revascularisation: 5-year outcomes of the BIOSCIENCE randomised trial. Lancet. 2018 Sep 1;392(10149):737-746. doi: 10.1016/S0140-6736(18)31715-X. Epub 2018 Aug 28.
- Derived from this study: PubMed 37192697Haner JD, Rohla M, Losdat S, Iglesias JF, Muller O, Eeckhout E, Kurz D, Weilenmann D, Kaiser C, Tapponnier M, Roffi M, Heg D, Windecker S, Pilgrim T. Ultrathin-strut vs thin-strut drug-eluting stents for multi and single-stent lesions: A lesion-level subgroup analysis of 2 randomized trials. Am Heart J. 2023 Sep;263:73-84. doi: 10.1016/j.ahj.2023.05.004. Epub 2023 May 14.
- Derived from this study: PubMed 36807456Iglesias JF, Muller O, Losdat S, Roffi M, Kurz DJ, Weilenmann D, Kaiser C, Heg D, Windecker S, Pilgrim T. Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial. Catheter Cardiovasc Interv. 2023 Mar;101(4):687-700. doi: 10.1002/ccd.30600. Epub 2023 Feb 19.
- Derived from this study: PubMed 33653633Iglesias JF, Heg D, Roffi M, Degrauwe S, Tuller D, Muller O, Brinkert M, Cook S, Weilenmann D, Kaiser C, Cuculi F, Valgimigli M, Juni P, Windecker S, Pilgrim T. Five-Year Outcomes With Biodegradable-Polymer Sirolimus-Eluting Stents Versus Durable-Polymer Everolimus-Eluting Stents in Patients With Acute Coronary Syndrome: A Subgroup Analysis of the BIOSCIENCE Trial. Cardiovasc Revasc Med. 2022 Jan;34:3-10. doi: 10.1016/j.carrev.2021.02.008. Epub 2021 Feb 25.
- Derived from this study: PubMed 31696762Iglesias JF, Heg D, Roffi M, Tuller D, Lanz J, Rigamonti F, Muller O, Moarof I, Cook S, Weilenmann D, Kaiser C, Cuculi F, Valgimigli M, Juni P, Windecker S, Pilgrim T. Five-Year Outcomes in Patients With Diabetes Mellitus Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents. J Am Heart Assoc. 2019 Nov 19;8(22):e013607. doi: 10.1161/JAHA.119.013607. Epub 2019 Nov 7.
- Derived from this study: PubMed 31525083Iglesias JF, Heg D, Roffi M, Tuller D, Noble S, Muller O, Moarof I, Cook S, Weilenmann D, Kaiser C, Cuculi F, Haner J, Juni P, Windecker S, Pilgrim T. Long-Term Effect of Ultrathin-Strut Versus Thin-Strut Drug-Eluting Stents in Patients With Small Vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Subgroup Analysis of the BIOSCIENCE Randomized Trial. Circ Cardiovasc Interv. 2019 Aug;12(8):e008024. doi: 10.1161/CIRCINTERVENTIONS.119.008024. Epub 2019 Aug 6.
- Derived from this study: PubMed 26823484Koskinas KC, Siontis GC, Piccolo R, Franzone A, Haynes A, Rat-Wirtzler J, Silber S, Serruys PW, Pilgrim T, Raber L, Heg D, Juni P, Windecker S. Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients. Circ Cardiovasc Interv. 2016 Feb;9(2):e003255. doi: 10.1161/CIRCINTERVENTIONS.115.003255.
- Derived from this study: PubMed 25825008Campos CM, Costa F, Garcia-Garcia HM, Bourantas C, Suwannasom P, Valgimigli M, Morel MA, Windecker S, Serruys PW. Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials. Circ Cardiovasc Interv. 2015 Apr;8(4):e002279. doi: 10.1161/CIRCINTERVENTIONS.114.002279.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Windecker principal investigator
Department of Cardiology, Bern University Hospital, Switzerland
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sirolimus-eluting stent with a bioresorbable polymer (Orsiro) and Everolimus-eluting stent with a durable polymer in people with Coronary Artery Disease and Angina Pectoris, run by Insel Gruppe AG, University Hospital Bern at 9 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01443104, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2018.