Ignite Creation Date:
2024-05-06 @ 2:25 AM
Last Modification Date:
2024-10-26 @ 11:18 AM
Study NCT ID:
NCT02049229
Status:
UNKNOWN
Last Update Posted:
2015-06-02
First Post:
2014-01-28
Brief Title:
Comparison of Titanium-Nitride-Oxide Coated Bio-Active-Stent Optimax to the Drug Everolimus -Eluting Stent Synergy in Acute Coronary Syndrome
Sponsor:
The Hospital District of Satakunta
Organization:
The Hospital District of Satakunta
Study Overview
Official Title:
Comparison of Titanium-Nitride-Oxide Coated Bio-Active-Stent Optimax to the Drug Everolimus -Eluting Stent Synergy in Acute Coronary Syndrome
Status:
UNKNOWN
Status Verified Date:
2015-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TIDES-ACS
Brief Summary:
The purpose of the prospective randomized and a multicenter trial is to compare clinical outcome in patients presenting with ACS treated with PCI using Optimax-BAS versus Synergy-EES
Second objective is to explore whether the Optimax-BAS use is superior compared with Synergy-EES use with respect of hard end points cardiac death MI and major bleeding
Second objective is to explore whether the Optimax-BAS use is superior compared with Synergy-EES use with respect of hard end points cardiac death MI and major bleeding
Detailed Description:
Coronary artery disease CAD is the most frequent cause of death accounting for approximately 13 of all deaths In western countries the incidence of ST-segment elevation myocardial infarction STEMI is around 77100 000year whereas in patients with non-ST-segment elevation acute coronary syndrome NSTE-ACS the incidence is 132100 000year Thus the incidence of STEMI is decreasing while there is a concomitant increase in the incidence of NSTE-ACS NSTE-ACS and STEMI are usually considered to be different entities but recent reports suggested that the prognosis of either subgroup of MI is similar despite different management strategies In STEMI primary percutaneous coronary intervention PCI is the recommended reperfusion therapy over fibrinolysis if performed by an experienced team within 2 hours of first medical contact Treatment of patients with NSTE-ACS is based on their risk of acute thrombotic complications A clear benefit from early angiography 48 h and PCI has been reported in the high-risk patients However deferral of interventions does not improve outcome In addition routine stenting is recommended on the basis of the predictability of the results and its safety Consensus has emerged that early PCI use results in favourable outcomes especially in high-risk patients The ESC guidelines for NSTE-ACS were updated in 20113 and for STEMI in 2012 Currently PCI is the preferred reperfusion strategy in patients with both acute STEMI and NSTE-ACS
Drug-eluting stents DES have been shown to reduce in-stent restenosis after PCI compared to bare metal stents BMS Over the previous decade the appearance of first-generation drug-eluting stents Taxus Cypher in scene has revolutionized the practice of coronary intervention resulting in a reduction of restenosis rates by one-half to two-thirds at 5 years follow-up amounting to roughly 10-15 need for target vessel revascularization following DES at long-term However early randomized first-generation-DES trials excluded patients with acute myocardial infarction MI even though invasive approach is currently the preferred method for treatment of acute MI Later randomized trials and meta-analyses of the clinical trials on the use of DES for treatment of acute STEMI demonstrated that the use of DES is safe and improves clinical outcomes mainly by decreasing the risk of re-intervention compared with BMS However accumulating evidence from meta-analyses and registries has questioned the long-term safety of first-generation DES raising concerns about a higher risk of late - and very late - stent thrombosis ST a potentially life-threatening complication
A further step forward was taken with the design of second-generation DES In SPIRIT I-III trials everolimus-eluting stent EES showed promising mid-term clinical outcome in selected patient groups resulting in FDA approval Newer second generation DES are now available in every day practice in interventional cardiology In this context Xience-V-EES significantly reduced late lumen loss as assessed by angiography as compared with the paclitaxel-eluting stents Taxus with non-inferior rates of a composite outcome of safety and efficacy Subsequent randomized trials demonstrated that as compared with first-generation DES Xience-V-EES was able to reduce both the restenosis and ST rates in overall elective patient population In Examination trial Xience-V-EES showed reduced rates of repeat revascularization and ST in STEMI patients when compared with traditional BMS On the other hand novel Promus-Element-EES has showed to be non-inferior when compared with Xience-V-EES in recent all comers-trial The Promus-Element stent uses the identical drug coating formulation and drug dose density as the Xience-V- stent
Although DES delivering antiproliferative drugs from adurable polymer have significantly reduced restenosis compared with BMS with no apparent increase in the risk of adverse events durable polymers have been associated with a hypersensitivity reaction delayed healing and incomplete endothelialization that may contribute to an increased risk of late 30 days to 1 year and very late beyond 1 year stent thrombosis compared with BMS A number of stent technologies are being developed in an attempt to modify the proposed mediators of late thrombotic events including bioabsorbable polymers nonpolymeric stent surfaces and bioabsorbable stents Synergy-EES is a novel Promus-Element stent platform that deliveres everolimus from an ultrathin bioabsorbable polymer applied to the abluminal surface In the randomized EVOLVE trial the SYNERGY stent was noninferior to the PROMUS Element stent for the primary angiographic endpoint of in-stent late loss at 6 months Clinical event rates were low and comparable with no stent thrombosis observed These results support the safety and efficacy of the abluminal bioabsorbable polymer SYNERGY EES for the treatment of patients with de novo coronary artery lesions
The safety of titanium-nitride-oxide-coated bioactive stents Titan-2-BAS has been established in several reports from real-life unselected populations Interestingly prospective studies demonstrated an even better outcome with Titan-2-BAS as compared with paclitaxel-eluting stents Taxus in high-risk patients with complex coronary lesions and in patients presenting with acute myocardial infarction MI The recent BASE-ACS trial demonstrated that in patients undergoing early PCI for acute coronary syndrome ACS the insertion of Titan-2-BAS was non-inferior to Xience-V-EES concerning the occurrence of the primary composite endpoint of MACE at 12 months follow-up The relative risk ratio of MACE for Titan-2-BAS was 107 a 06-percentage-point absolute risk difference as compared with Xience-V-EES a difference that met the chief aim of the trial for non-inferiority of Titan-2-BAS in reducing MACE in this patient category Moreover albeit not adequately powered to address the individual components of safety and efficacy non-fatal MI occurred significantly less frequently and ARC-definite ST trended to be lower in the Titan-2-BAS group as compared with the Xience-V-EES group On the other hand stent coating with compounds like titanium-nitride-oxide seem to decrease acute surface thrombogenicity and reduce in-stent restenosis when compared with conventional stainless steel stents Optimax stent is a novel next generation BAS in which a thicker layer of titanium-nitride-oxide coating is inserted over the stent struts The rationale of this is to obtain more efficient and rapid vascular healing at the site of the stent implantation
After the initial enthusiasm for DES based on their impressive reduction in restenosis there was increasing concern about an increased risk for late ST Consequently the recommendation for the duration of dual antiplatelet therapy with aspirin and clopidogrel DAPT was incrementally extended from initially 3 months for Cypher-DES and 6 months for Taxus-DES to recently at least 12 months for all DES Not commonly cardiologists recommend indefinite DAPT if the patient has no bleeding complications during the first 12 months The need for long-term DAPT is costly and remains the Achilles heel of DES namely increase risk of bleeding complication Newer generation of stents have shown impressively low ST rates and therefore the excessive bleeding risk of DAPT is being reconsidered Current guidelines recommend that oral thienopyridine clopidogrel prasugrel or ticagrelol must be continued for up to 12 months after STEMI with a strict minimum of 1 month for patient receiving BMS and 6 months for patients receiving DES
Because early discontinuation of DAPT is recognized as the most potent predictor of DES thrombosis discussion with the patient regarding the need for and duration of DAPT and the ability to comply with and tolerate DAPT is mandatory before DES implantation When the patient is unable to tolerate or comply with DAPT as well as when surgery is anticipated within 12 months of DES implantation or when the individual bleeding risk is high BMS implantation should be preferred In the attempt to increase biocompatibility of BMS therefore reducing the risk of ST as well as of restenosis without use of polymer-eluted drugs various coatings have been used Among them diamond-like carbon-coated stent and above-mentioned titanium nitric oxide-coated stent have shown promising results making therefore a point for DAPT duration shorter than the 3 months commonly recommended for BMS
The purpose of the prospective randomized and a multicenter trial is to compare clinical outcome in patients presenting with ACS treated with PCI using Optimax-BAS versus Synergy-EES Second objective is to explore whether the Optimax-BAS use is superior compared with Synergy-EES use with respect of hard end points cardiac death MI and major bleeding
Long-term 12 months follow-up of patients presenting with ACS both STEMI and NSTE-ACS receiving either Optimax-BAS or Synergy-EES will result in comparable clinical outcome non-inferiority MACE including cardiac death MI and repeat revascularization Secondly the strategy of Optimax-BAS use is superior to Synergy-EES use during the 18 months of follow-up in hard end points superiority cardiac death MI and major bleeding
Drug-eluting stents DES have been shown to reduce in-stent restenosis after PCI compared to bare metal stents BMS Over the previous decade the appearance of first-generation drug-eluting stents Taxus Cypher in scene has revolutionized the practice of coronary intervention resulting in a reduction of restenosis rates by one-half to two-thirds at 5 years follow-up amounting to roughly 10-15 need for target vessel revascularization following DES at long-term However early randomized first-generation-DES trials excluded patients with acute myocardial infarction MI even though invasive approach is currently the preferred method for treatment of acute MI Later randomized trials and meta-analyses of the clinical trials on the use of DES for treatment of acute STEMI demonstrated that the use of DES is safe and improves clinical outcomes mainly by decreasing the risk of re-intervention compared with BMS However accumulating evidence from meta-analyses and registries has questioned the long-term safety of first-generation DES raising concerns about a higher risk of late - and very late - stent thrombosis ST a potentially life-threatening complication
A further step forward was taken with the design of second-generation DES In SPIRIT I-III trials everolimus-eluting stent EES showed promising mid-term clinical outcome in selected patient groups resulting in FDA approval Newer second generation DES are now available in every day practice in interventional cardiology In this context Xience-V-EES significantly reduced late lumen loss as assessed by angiography as compared with the paclitaxel-eluting stents Taxus with non-inferior rates of a composite outcome of safety and efficacy Subsequent randomized trials demonstrated that as compared with first-generation DES Xience-V-EES was able to reduce both the restenosis and ST rates in overall elective patient population In Examination trial Xience-V-EES showed reduced rates of repeat revascularization and ST in STEMI patients when compared with traditional BMS On the other hand novel Promus-Element-EES has showed to be non-inferior when compared with Xience-V-EES in recent all comers-trial The Promus-Element stent uses the identical drug coating formulation and drug dose density as the Xience-V- stent
Although DES delivering antiproliferative drugs from adurable polymer have significantly reduced restenosis compared with BMS with no apparent increase in the risk of adverse events durable polymers have been associated with a hypersensitivity reaction delayed healing and incomplete endothelialization that may contribute to an increased risk of late 30 days to 1 year and very late beyond 1 year stent thrombosis compared with BMS A number of stent technologies are being developed in an attempt to modify the proposed mediators of late thrombotic events including bioabsorbable polymers nonpolymeric stent surfaces and bioabsorbable stents Synergy-EES is a novel Promus-Element stent platform that deliveres everolimus from an ultrathin bioabsorbable polymer applied to the abluminal surface In the randomized EVOLVE trial the SYNERGY stent was noninferior to the PROMUS Element stent for the primary angiographic endpoint of in-stent late loss at 6 months Clinical event rates were low and comparable with no stent thrombosis observed These results support the safety and efficacy of the abluminal bioabsorbable polymer SYNERGY EES for the treatment of patients with de novo coronary artery lesions
The safety of titanium-nitride-oxide-coated bioactive stents Titan-2-BAS has been established in several reports from real-life unselected populations Interestingly prospective studies demonstrated an even better outcome with Titan-2-BAS as compared with paclitaxel-eluting stents Taxus in high-risk patients with complex coronary lesions and in patients presenting with acute myocardial infarction MI The recent BASE-ACS trial demonstrated that in patients undergoing early PCI for acute coronary syndrome ACS the insertion of Titan-2-BAS was non-inferior to Xience-V-EES concerning the occurrence of the primary composite endpoint of MACE at 12 months follow-up The relative risk ratio of MACE for Titan-2-BAS was 107 a 06-percentage-point absolute risk difference as compared with Xience-V-EES a difference that met the chief aim of the trial for non-inferiority of Titan-2-BAS in reducing MACE in this patient category Moreover albeit not adequately powered to address the individual components of safety and efficacy non-fatal MI occurred significantly less frequently and ARC-definite ST trended to be lower in the Titan-2-BAS group as compared with the Xience-V-EES group On the other hand stent coating with compounds like titanium-nitride-oxide seem to decrease acute surface thrombogenicity and reduce in-stent restenosis when compared with conventional stainless steel stents Optimax stent is a novel next generation BAS in which a thicker layer of titanium-nitride-oxide coating is inserted over the stent struts The rationale of this is to obtain more efficient and rapid vascular healing at the site of the stent implantation
After the initial enthusiasm for DES based on their impressive reduction in restenosis there was increasing concern about an increased risk for late ST Consequently the recommendation for the duration of dual antiplatelet therapy with aspirin and clopidogrel DAPT was incrementally extended from initially 3 months for Cypher-DES and 6 months for Taxus-DES to recently at least 12 months for all DES Not commonly cardiologists recommend indefinite DAPT if the patient has no bleeding complications during the first 12 months The need for long-term DAPT is costly and remains the Achilles heel of DES namely increase risk of bleeding complication Newer generation of stents have shown impressively low ST rates and therefore the excessive bleeding risk of DAPT is being reconsidered Current guidelines recommend that oral thienopyridine clopidogrel prasugrel or ticagrelol must be continued for up to 12 months after STEMI with a strict minimum of 1 month for patient receiving BMS and 6 months for patients receiving DES
Because early discontinuation of DAPT is recognized as the most potent predictor of DES thrombosis discussion with the patient regarding the need for and duration of DAPT and the ability to comply with and tolerate DAPT is mandatory before DES implantation When the patient is unable to tolerate or comply with DAPT as well as when surgery is anticipated within 12 months of DES implantation or when the individual bleeding risk is high BMS implantation should be preferred In the attempt to increase biocompatibility of BMS therefore reducing the risk of ST as well as of restenosis without use of polymer-eluted drugs various coatings have been used Among them diamond-like carbon-coated stent and above-mentioned titanium nitric oxide-coated stent have shown promising results making therefore a point for DAPT duration shorter than the 3 months commonly recommended for BMS
The purpose of the prospective randomized and a multicenter trial is to compare clinical outcome in patients presenting with ACS treated with PCI using Optimax-BAS versus Synergy-EES Second objective is to explore whether the Optimax-BAS use is superior compared with Synergy-EES use with respect of hard end points cardiac death MI and major bleeding
Long-term 12 months follow-up of patients presenting with ACS both STEMI and NSTE-ACS receiving either Optimax-BAS or Synergy-EES will result in comparable clinical outcome non-inferiority MACE including cardiac death MI and repeat revascularization Secondly the strategy of Optimax-BAS use is superior to Synergy-EES use during the 18 months of follow-up in hard end points superiority cardiac death MI and major bleeding
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None