The primary purpose of the study is Optical Frequency Domain Imaging (OFDI) investigation of strut coverage of the sirolimus-eluting stent with biodegradable polymer at 1, 2 and 3 months after stent implantation This study is the pilot study to…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is OFDI assessed percent stent strut coverage at 3 months
post procedure.
Hypothesis: <20% uncovered struts at 3 months post procedure
NOTE: the Primary endpoint will be assessed for all single stent lesions.
Secondary outcome
1. Number (%) of stent strut coverage at 1 and 2 months
2. Number (%) of stented lesions which have >10 % uncovered stent struts at 1,
2 or 3 months
3. Number (%) of stented lesions which have >20% uncovered struts at 1, 2 or 3
months
4. Percentage of acquired malapposed struts at 1, 2 and 3 months
5. Amount of in-stent intimal hyperplasia (mm3) at 1, 2 and 3 months
6. Amount of in-segment intimal hyperplasia (mm3) at 1, 2 an d 3 months
7. Neo-intimal thickness (µm) at 3 months
8. In-stent late-lumen loss at 3 months by QCA
9. In-segment late lumen loss at 3 months by QCA
10. Target Lesion Revascularization (TLR) at 1, 3, and 12 months post-procedure;
11. Target Vessel Revascularization (TVR) at 1, 3 and 12 months post-procedure;
12. Target Lesion Failure (TLF), composite endpoint of Cardiac Death, target
vessel related Myocardial infarction (MI) and Clinically Indicated TLR at 1, 3
and 12 months post-procedure;
13. Major Cardiac Adverse Events (MACE) defined as cardiac death, MI (Q wave
and non-Q wave), emergent coronary artery bypass surgery, or target vessel
revascularization (TVR) at 1, 3 and 12 months post-procedure.
14. Stent thrombosis at 1, 3 and 12 months post-procedure;
NOTE: all secondary endpoints will be assessed for single stent lesions and
overlapping stent lesions.
Background summary
Stent thrombosis is a rare, but serious event as it is linked to myocardial
infarction, sudden death and heart failure. It occurs in 0.7-1.0% of the PCI
procedures within 1 year and has an annual incidence rate of 0.1 to 0.7%
thereafter, depending on the type of stent is used. Therefore, prevention of
stent thrombosis in the early (<30 days after PCI), late (>30 < 360 days) and
very late (>360 days) phase is of important clinical relevance.
Currently dual antiplatelet therapy (DAPT) is given for at least of 9-12 months
after coronary drug-eluting stent implantation in order to lower the risk for
early and late stent thrombosis, though this merely based on non-randomised
observations and expert opinion. Furthermore, DAPT therapy is not a 100%
protective therapy, as stent thrombosis still occurs under DAPT regimen. And
whether extended DAPT beyond one year after DES implantation is beneficial
remains to be determined, but is very likely to be associated with a higher
bleeding risk for the patient.
Stent related factors to stent thrombosis are the amount of uncovered stent
struts and the extend of malapposed stent struts to the vessel wall. Both are
highly related to the type of stent used, in which the polymer (in combination
with the drug) causes incomplete healing of the vessel wall, chronic
inflammation or hypersensitivity reaction and eventually incomplete
re-endothelialization or incomplete coverage and embedment of the stent in the
vessel wall. Usage of more biocompatible durable polymers or biodegradable
polymers have the potential to overcome the above mentioned triggers for stent
related factors of stent thrombosis. This has recently been proven in
comparative stent studies, like COMPARE I, SPIRIT IV and LEADERS, in which the
more biocompatible or biodegradable polymer coated drug-eluting stents had a
significantly lower amount of stent thrombosis compared to the first generation
drug-eluting stents or were at least equivalent to the proven biocompatible
durable fluoropolymer of the thin-strut Cobalt-Chromium everolimus-eluting
stent (COMPARE II, RESOLUTE AC).
OCT or OFDI are new intravascular imaging modalities with a much higher
resolution compared to intravascular ultrasound (IVUS). These new techniques
have been used to investigate the amount of coverage and the amount of
malaposition of the stent struts.
Though there are no universal accepted criteria for the relationship between
stent coverage or malapposition and stent thrombosis, recent studies with the
newer generation drug-eluting stents have shown that stent coverage is >90% and
malapposition is < 3 % of the total investigated stent struts by OCT at 6 to 13
months post implantation.
Purpose of this pilot study is to investigate the absolute stent coverage at 1,
2 and 3 months after stent implantation of a new thin strut Cobalt-Chromium
sirolimus-eluting stent with an abluminal biodegradable polymer, which resolves
in 3 month time. After 3 months, when the polymer is dissolved and the drug is
released, an inert bare metal stent resides. This will pave the way for a large
scale randomized trial, showing that a 3 month DAPT regimen will be as safe as
6 to 9 months DAPT and potentially will result in less bleedings.
OFDI Analysis
In the last decade the powerful imaging technique - optical frequency domain
imaging - has gained popularity and is frequently used to study pattern of
vessel healing after DES implantation and also to assess potential underlying
mechanisms for adverse events, particularly those causing stent thrombosis. It
has been hypothesized that delayed healing and insufficient strut coverage are
predisposing factors for stent thrombosis development.
In a systematic review of strut coverage of different DES, assessed by optical
coherence tomography at 6 months, the first generation sirolimus eluting Cypher
stent and paclitaxel eluting Taxus stent showed respectively 10.86% and 5.49%
of uncovered struts. At 9 months Cypher stent had 8.12% uncovered struts while
Xience everolimus eluting stent had 3.12%, similar to TCD-10023 stent at 6
months (3.8%). The overall frequency of malapposed struts in TCD-10023 stent
was 1.66% at 6 months being among the lowest reported.1 The result obtained in
RESOLUTE all-comer trials assessing DES coated with zotarolimus (Endeavor
Resolute) and everolimus (Xience) eluting stents, showed coverage rate of 92.6%
and 94.2% respectively.2 This study tested strut coverage at 13 months
post-stent implantation in two stents having similar design to TCD-10023 stent,
except that both have permanent polymers indicating that TCD-10023 has strong
tendency towards good strut coverage as even at 6-months percentage of covered
struts was higher.
Guagliumi et al. studied the impact of stent alloys on human vascular response
to everolimus by comparing two DES with different platforms (cobalt chromium -
Xience DES and platinum chromium-Promus Element), with similar coating and drug
formulation. They found that at 6 months both stents had similar behaviour
towards the vessel wall with low rate of strut malapposition (1.51% in platinum
chromium and 1.80% in cobalt-chromium). Those findings are also very similar to
1.66% in TCD-10023 DES. At the same time the percentage of uncovered struts was
higher than in TCD-10023 (8.5% and 5.9% in platinum-and cobalt-chromium
respectively).
All those findings indicate excellent results of the TCD-10023 stent, which
considering the design concept will allow us to investigate the safety profile
within 3 months after implantation and potentially to investigate shorter DAPT
regimens and therefore less bleeding risk after stent implantation without
compromising safety.
Study objective
The primary purpose of the study is Optical Frequency Domain Imaging (OFDI)
investigation of strut coverage of the sirolimus-eluting stent with
biodegradable polymer at 1, 2 and 3 months after stent implantation
This study is the pilot study to assess feasibility of shorter DAPT after PCI
with this new stent.
Study design
Prospective, single arm, multicenter, open label study with adaptive design.
All patients will undergo angiographic follow-up at 3 months, OFDI imaging
after baseline and at 1, 2 and 3 months, and clinical follow-up out to 1 year.
Intervention
All eligible patients will be treated with the study stent: sirolimus eluting
coronary stent TCD-10023 with biodegredable polymer. No comparator arm.
Study burden and risks
Nature and extend of the burden:
Before and after stent implantation a blood test (approximately 15 ml for
analysis of cardiac enzymes) and ECG will be performed according to the
standard procedure of the hospital. An OFDI-evaluation of the treated lesions
will be performed after stent implantation. Dual antiplatelet therapy (DAPT)
will be prescribed for a period of at least 6 months according to hospital
routine practice. The patients will be asked to visit the hospital at 3 months
for an evaluation of patient's general well-being and a routine physical
examination, and for angiographic and OFDI evaluation of all treated lesions.
At 12 months patients will receive phone call from the research personnel to
ask about their general well-being and health condition.
Possible risks associated with participation:
The potential risks of the stent implantation in this study are not different
from the potential risks associated with the standard procedure of stent
placement and they may include the following:
* Major bleeding from the groin site depends on whether blood thinning drugs
are used (4 in 100 patients)
* Death (less than 7 in 1,000 patients)
* Emergency bypass surgery (15 in 10,000 patients )
* Heart attack (4 in 1,000 patients)
* Stroke (2 in 1000 patients) risk may vary depending on whether blood thinning
drugs are used.
* There is also no guarantee that the stent will keep the vessel open and
reduce subsequent re-narrowing of the artery
Although very unlikely, there may be unforeseeable risks that are not known at
this time. The results of the stent placement can not be guaranteed 100%. If
the procedure is not successful, repeat intervention(s) and/or coronary by-pass
surgery may be necessary.
Any coronary angiogram involves the use of radiation as part of the special
X-Ray procedure. The dose of radiation received from one coronary angiogram is
equivalent to two years natural background radiation.
The risks for the angiogram are:
* Death (1 in 10,000 patients)
* Emergency angioplasty +/- stent (1 in 1,000 patients)
* Emergency bypass surgery (1 in 10,000 patients)
* Heart Attack (5 in 10,000 patients)
* Stroke (7 in 10,000 patients)
* Bleeding (4 in 100 patients)
The risks related to the use of the OFDI catheter are not different to those of
a balloon dilatation and/or stenting procedure alone. It is important to inform
you however that extra catheters will be introduced into your coronary
arteries. This implies a small risk of harming the vessel; patients may feel
some chest pain (caused by cramp of the coronary artery). Damage to or movement
of the stent are possible. Upon occurrence of these complaints these can
quickly be relieved by using medication. Exceptionally implantation of another
stent or bypass surgery may be necessary.
Benefits associated with participation:
Patients will not have any immediate benefit from participating in this
clinical investigation except that the treating physician will follow up on the
patients' medical condition on a regular base so every sign of illness can be
detected in time. The results of this study will be used for scientific
purposes which will result in increased knowledge on the best treatment
procedures and medications for the medical conditions patients are suffering.
Interleuvenlaan 40
Leuven 3001
BE
Interleuvenlaan 40
Leuven 3001
BE
Listed location countries
Age
Inclusion criteria
1. Patient is at least 18 years old;
2. Patients is a suitable candidate for PCI;
3. Patient has multi-vessel disease with >=2 de-novo lesions in native coronary arteries suitable for treatment with TCD-10023 DES;
4. Target lesions are suitable for OFDI examination;
5. Patient requires staged procedure between 3-5 weeks after baseline procedure, according to investigator*s judgement;
6. Target vessel reference diameter is between 2.5 - 4.0 mm (visual assessment);
7. Patient has provided written informed consent;
8. Patient is affiliated to social security or equivalent system (France only).
Exclusion criteria
1. Patient has known allergy to sirolimus, cobalt, chromium, nickel, or contrast agent (that cannot be adequately premedicated);
2. Patient is not a suitable candidate for use of DAPT because of active or recent bleedings or for use of vitamin K antagonist, like warfarin, dabigatran, rivaroxaban or acenocoumarol;
3. Patient is presenting with STEMI at baseline procedure;
4. Patient has Killip class > 1 at admission;
5. Patient is in cardiogenic shock;
6. Patient is a female of childbearing potential;
7. Patient has life expectancy of less then 1 year;
8. Patient is expected to undergo major surgery within 3 months;
9. Patient has Left Main disease >= 50%;
10. Target lesion at bifurcation requiring 2 stents technique;
11. Target lesions are severely calcified;
12. Target lesion is aorta-ostially located (within 3 mm of vessel origin);
13. Patient has renal failure defined as estimated Glomerular Filtration Rate (eGFR) <50 mL/min/1.73m²;
14. Target lesions require preparation other than balloon pre-dilatation;
15. Patient is currently participating in an investigational drug or device study 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 become commercially available since then, are not considered investigational trials;
16. In the Investigator*s opinion patient has (a) co-morbid condition(s) that could limit the patient*s ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study;
17. Patient is under judicial protection (France only).
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 |
|---|---|
| ClinicalTrials.gov | NCT01844843 |
| CCMO | NL44520.101.13 |