The study objective is to assess the safety and efficacy of the Svelte Drug-Eluting Coronary Stent Integrated Delivery System (IDS) compared to the Resolute IntegrityTM Drug-Eluting Stent in patients with single, de novo coronary artery lesions.
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint is angiographic Target Vessel Failure (TVF) at
6-months post-procedure; the primary efficacy endpoint is angiographic in-stent
Late lumen Loss (LL) at 6-months post-procedure.
Secondary outcome
Safety:
•Clinically-driven Target Lesion Revascularization (TLR) at 1 and 6-months and
yearly through 5-years post-procedure;
•Composite of cardiac death, MI attributed to the target vessel and clinically
driven TLR at 1 and 6-months post-procedure and yearly up to 5-years;
•Composite of all-cause mortality, any MI and any revascularization, TVR or
revascularization of non-target vessels at 5-years post-procedure;
•Stent thrombosis at 1 and 6-months and yearly for 5-years post-procedure;
•Acute success rates:
-Device Success: Attainment of < 30% final residual stenosis of the
target lesion;
-Direct Stenting Success: Attainment of < 30% final residual stenosis of
the target lesion without pre-dilatation;
-Lesion Success: Attainment of < 30% final residual stenosis of the
target lesion using any stent with or without other interventional devices;
-Procedure Success: Lesion success and no in-hospital MACE.
Efficacy:
•In-stent and in-segment angiographic binary restenosis at 6-months
post-procedure;
•In-stent and in-segment Minimum Lumen Diameter (MLD) at 6-months
post-procedure;
•In-segment Late lumen Loss (LL) at 6-months post-procedure;
•Neointimal hyperplasia (% lumen volume) at 6-months post-procedure measured by
optical coherence tomography (OCT) in patients treated with the Svelte
Drug-Eluting Coronary Stent Integrated Delivery System (IDS); and
•Strut coverage (% of struts malapposed, protruding non-covered, protruding
covered, non-protruding covered) at 6-months post-procedure measured by OCT in
patients treated with the Svelte Drug-Eluting Coronary Stent Integrated
Delivery System (IDS).
Background summary
Coronary artery stenting has evolved substantially since the first use of
stents as an adjunct to balloon angioplasty in the early 1990s. The performance
of coronary stents has improved considerably, with stenting now the primary
mode of revascularization in percutaneous coronary interventions (PCI).
Percutaneous transluminal coronary angioplasty (PTCA) has been widely used to
treat patients with symptomatic coronary artery disease (CAD). The major
limitations of PTCA (abrupt closure, PTCA-induced intimal dissection and
restenosis) have been addressed through the development of coronary stents.
Steady improvements in stent design and adjunctive medical therapies over the
preceding two decades have resulted in marked improvement in the safety and
efficacy of PCIs. Estimates for in-hospital adverse events (death, myocardial
infarction, stent thrombosis) are less than 1% in a recent U.S. multicenter
registry.
Conventional PCI practice usually includes pre-dilatation of the target lesion
prior to stent placement. This convention is dictated, in part, by the
characteristics of first generation stents, which were higher profile, stiff
devices which could not reliably be delivered to lesions. Additionally, these
stents were hand-crimped onto balloon catheters, resulting in tenuous
securement of the stents to their delivery systems. These features made
pre-dilatation of the target lesion virtually mandatory to allow stent
delivery. However current generation stents and stent delivery systems
increasingly allow for stent placement without pre-dilatation, a strategy known
as *direct stenting*.
Direct stenting is currently employed in approximately 30-40% of PCI procedures
and has been compared to conventional stenting (using pre-dilatation) in
numerous observational studies and randomized trials using bare metal stents.
In select lesions (lower degrees of lesion calcification with minimal vessel
tortuosity), high rates of technical and procedural success have been observed.
Additionally, significant reductions in procedure time, radiation exposure,
contrast administration, and cost have been realized with comparable 6 -
12-month clinical outcomes.
While PCI with stenting for CAD is associated with high rates of clinical
success and low procedural morbidity, the risks of radiation exposure, contrast
use and access site bleeding, as well as overall procedure costs in general,
are not negligible. Clinical risks are incrementally higher in patients with
advanced age multi-vessel disease requiring staged procedures, chronic kidney
disease and peripheral arterial disease making minimization of these risks of
paramount importance.
A direct stenting strategy offers the possibility to further reduce the risk of
adverse
events in high-risk PCI patients, decreasing contrast requirements and
radiation dose to the operator and patient while providing the added benefit of
reducing procedural time and cost.
The Svelte Medical Systems Drug-Eluting Coronary Stent Integrated Delivery
System (IDS) is a balloon-expandable, thin-strut cobalt-chromium (CoCr)
coronary stent eluting sirolimus from a fully bio-erodible drug carrier mounted
on a low-profile, fixed-wire balloon catheter. The system has a 0.014* lesion
entry profile, is compatible with 5 French (minimum ID .056*) or larger guiding
catheters and is indicated for direct stenting.
Fixed-wire systems were introduced in the early days of PCI to provide lower
profile options in the event of abrupt vessel closure and treatment of more
complex lesions. As stents evolved throughout the 1990s, conventional PTCA
balloons became mostly relegated to pre-and post-dilate lesions, which drove
the market toward the use of guidewire-based devices. The need to re-cross
lesions for further treatment (i.e. for post-dilatation or secondary stenting)
additionally limited use of the fixed-wire platform. Reports of wire fractures
and difficulties with balloon deflation further dampened enthusiasm for these
early fixed-wire systems. These early limitations of fixed-wire technology,
along with the development of lower profile guidewire-based systems, resulted
in the abandonment of the fixed-wire balloon catheter. However in an era where
more challenging lesions are being treated and even greater value is being
placed on the clinical and procedural benefits associated with direct stenting,
the Svelte IDS represents an important advance in the improvement of PCI.
Advanced fixed-wire and balloon technologies coupled with a low-profile, highly
flexible stent, make the Svelte IDS the first material improvement in stent
delivery technology in more than a decade.
The current study is proposed in order to collect information about the safety
and performance of the Svelte IDS in the treatment of stenotic lesions in de
novo native coronary arteries. A large body of published data now exists to
demonstrate the superiority of drug-eluting stents (DES), and especially
sirolimus-eluting stents, over bare metal stents. However, in spite of the
clinical efficacy of DES, there are ongoing concerns regarding the long-term
biocompatibility of durable polymers, including polymers used on currently
commercialized DES. It is believed that these polymers may, in the long term,
incite inflammation, which could lead to late *catch-up* (restenosis) or late
stent thrombosis. Due to the concern with durable polymers, there is renewed
interest in developing DES with bio-erodible, non-inflammatory coatings.
The pharmacokinetics of the Svelte IDS have been carefully designed to mimic
drug release of the Cypher (Cordis/ Johnson & Johnson) and Xience (Abbott)
DES. The Svelte drug carrier is designed to erode in 9-12 months, leaving
behind only a thin-strutted cobalt chromium stent. The potential exists to
reduce lingering or late inflammation that may be caused by commercially
available durable polymers. This clinical trial is designed to assess the
safety and longer-term efficacy of the Svelte IDS, as described in greater
detail below.
The Svelte IDS represents a new, very low profile, highly deliverable coronary
stent platform allowing for direct stenting in the majority of coronary artery
lesions. In addition to the well-known benefits of direct stenting procedural
efficiencies realized with the Svelte IDS may provide substantial cost savings
as well as reductions in procedure time, radiation exposure (for patient and
operator), and bleeding complications. Use of the sirolimus-eluting version of
the Svelte IDS may further provide substantial reductions in long-term
restenosis and target lesion revascularization compared to the bare-metal stent
version of the system. The highly biocompatible and fully bio-erodible Svelte
drug carrier may also improve long-term safety and offer the potential to
reduce the need for long-term dual anti-platelet therapy. The safety and
efficacy of the Svelte IDS with bioerodible drug carrier will be assessed in
this study.
Study objective
The study objective is to assess the safety and efficacy of the Svelte
Drug-Eluting Coronary Stent Integrated Delivery System (IDS) compared to the
Resolute IntegrityTM Drug-Eluting Stent in patients with single, de novo
coronary artery lesions.
Study design
A prospective, randomized, active-control, multi-center clinical trial
comparing the safety and efficacy of the Svelte Drug-Eluting Coronary Stent
Integrated Delivery System (IDS) to that of the commercially available Resolute
IntegrityTM Drug-Eluting Stent. One hundred fifty-nine (159) patients (2:1
randomization Svelte IDS: Resolute IntegrityTM to establish non-inferiority in
the primary efficacy endpoint of in-stent late lumen loss) will be treated in
up to twenty (20) centers in Europe and Brazil, with clinical and angiographic
follow-up at 6-months to assess the primary endpoints of angiographic Target
Vessel Failure (TVF) and Late Lumen Loss (LL), as well as secondary safety and
efficacy endpoints. Additional clinical follow-up will take place at 1-month
and annually through 5-years.
Intervention
Angiography and coronary angioplasty.
Study burden and risks
Svelte has conducted risk analysis for the Svelte Drug-Eluting Coronary Stent
Integrated Delivery System (IDS) and concluded that from a technology,
construction, material, application, and design perspective intolerable risks
were either not inherent to the design of the device or were successfully
mitigated.
The bare-metal version of the Svelte IDS has obtained the CE Mark and is
commercially available in select accounts in Brazil and Europe, utilizing
either a radial and femoral approach.
2.1 Potential or Anticipated Adverse Events
Adverse events may be associated with the use of a coronary stent in native
coronary arteries:
• Abrupt vessel closure
• Access site pain, hematoma or hemorrhage
• Acute myocardial infarction
• Allergic reaction to anticoagulants or antiplatelet therapy, contrast medium,
or stent material
• Aneurysm, pseudoaneurysm, or arteriovenous fistula (AVF)
• Angina
• Arrhythmias, including VF and VT
• Cardiac tamponade
• Cardiogenic shock
• Death
• Emboli, distal (air, tissue or thrombotic emboli)
• Emergency surgery, coronary artery bypass or peripheral vascular
• Hemorrhage, requiring transfusion
• Hypotension/hypertension
• Infection, local and/or systemic
• Ischemia, myocardial
• Peripheral ischemia/peripheral nerve injury
• Pulmonary edema
• Renal failure
• Respiratory failure
• Restenosis of stented segment
• Vessel Spasm
• Stent embolization, misplacement, migration
• Stent thrombosis/occlusion (acute and subacute)
• Stroke/cerebrovascular accident/transient ischemic attack (TIA)
• Total occlusion of coronary artery
• Vessel trauma, dissection, perforation, rupture or injury, including coronary
Sirolimus, when prescribed as an oral medication, may interact with the
drugs/foods listed below. Medications that are strong inhibitors of CYP3A4
might reduce Sirolimus metabolism in vivo. Hence, co-administration of strong
inhibitors of CYP3A4 may increase the blood concentrations of Sirolimus.
• Antibiotics (ciprofloxacin, ofloxacin)
• Glucocorticoids
• HMGCoA reductase inhibitors (simvastatin, lovastatin)
• Cisapride (theoretical potential interaction)
• Sildenafil (Viagra®) (theoretical potential interaction)
• Antihistaminics (terfenadine, astemizole)
Central Avenue 675
New Providence NJ 07974
US
Central Avenue 675
New Providence NJ 07974
US
Listed location countries
Age
Inclusion criteria
1.Patient is >=18 years old;
2.Patient is eligible for percutaneous coronary intervention (PCI);
3.Patient is an acceptable candidate for emergent coronary artery bypass graft (CABG) surgery;
4.Patient has clinical evidence of ischemic heart disease, stable or unstable angina, silent ischemia, or a positive functional study;
5.Female subjects of childbearing potential must have a negative pregnancy test within 7-days before the trial procedure;
6.Patient or subject*s legal representative has been informed of the nature of the trial and agrees to its provisions and has provided written informed consent as approved by the Hospital Research Ethics Committee (HREC) of the respective investigational site; and
7.Patient agrees to comply with specified follow-up evaluations and to return to the same investigational site where the procedure was performed.
8.Patient has either a single target lesion, or two lesions (target and non-target) located in separate coronary arteries;
9.If a non-target lesion is treated, it must be treated first and only with commercially available PTCA balloons and/or stents. Post PCI of the non-target vessel, all of the following conditions must be met:
a.Residual diameter stenosis < 30%;
b.Absence of any angiographic complications;
c.Absence of ischemic symptoms; and
d.Absence of significant new arrhythmia or ECG monitoring changes suggestive of ischemia.
10.Reference vessel >= 2.5 mm and <= 3.5 mm in diameter by visual estimate;
11.Target lesion < 20 mm in length by visual estimate (the intention is to cover the entire lesion with one stent of adequate length); and
12.Target lesion stenosis >= 50% and < 100% by visual estimate.
Exclusion criteria
1.Patient is currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints
Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials;
2.The patient requires a staged procedure of the target vessel within 6-months or a staged procedure of a non-target vessel within 30-days post-procedure;
3.The target lesion requires treatment with a device other than PTCA prior to stent placement (such as, but not limited to, directional coronary atherectomy, excimer laser, rotational atherectomy, etc.);
4.Any DES deployment anywhere in the target vessel within the past 9-months;
5.Any BMS deployment anywhere in the target vessel within the past 6-months;
6.Any previous stent placement within 10 mm (proximal or distal) of the target lesion;
7.Myocardial infarction within 72-hours of the index procedure, with the exception of:
a.Patients who have had a STEMI and PCI to the culprit lesion may be included if they have a suitable lesion in another vessel, and have been clinically and hemodynamically stable for 72-hours;
b.Patients who have had a non-STEMI may be included if their troponin levels are within the laboratory normal range within 24-hours pre-procedure.
8.Co-morbid condition(s) that could limit the patient*s ability to participate in the trial or to comply with follow-up requirements, or impact the scientific integrity of the trial;
9.Concurrent medical condition with a life expectancy of less than 12-months;
10.Documented left ventricular ejection fraction (LVEF) <= 30%;
11.Unstable angina pectoris from an extra-cardiac cause (Braunwald Class A I-III);
12.Known allergies to the following: Acetylsalicylic acid (ASA), Clopidogrel bisulfate, Ticlopidine, Prasugrel, Rapamycin, Zotarolimus, PEAIII AcBz, Heparin/ Bivalirudin, or contrast agent (that cannot be adequately premedicated);
13.Platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3 or a WBC < 3.000 cells/mm3 or hemoglobin < 100g/l;
14.Acute or chronic renal dysfunction (serum creatinine > 170µmol/L);
15.History of a stroke or transient ischemic attack (TIA) within the prior 6-months;
16.Active peptic ulcer or upper gastrointestinal (GI) bleeding within the prior 6-months;
17.History of bleeding diathesis or coagulopathy or will refuse blood transfusions; and
18.Patients requiring ongoing anticoagulation with warfarin or dabigatran.
19.Total occlusion (TIMI 0 or 1);
20.Target vessel has angiographic evidence of thrombus
21.Target vessel is excessively tortuous or has heavy calcification;
22.Significant (> 50%) stenosis proximal or distal to the target lesion that might require revascularization or impede run off;
23.Target lesion is located in or supplied by an arterial or venous bypass graft;
24.Ostial target lesion (within 5.0 mm of vessel origin) or any location within the left main coronary artery;
25.Target lesion involves a side branch > 2.0 mm in diameter; and
26.Unprotected Left Main coronary disease (stenosis > 50%).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42184.078.12 |