The primary objective is to establish the non-inferiority of the Synergy stent relative to the Xience stent for prevention of MACE. The effect measure is the difference in the rate of MACE in patients randomized to treatment with the Synergy ( index…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Vascular therapeutic procedures
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is MACE rate, including death from any cause, MI, or
ischemia-driven target vessel revascularization (TVR) at 2 years after the
procedure.
Secondary outcome
• The individual events of the primary endpoint
• Procedure success (attainment of <30% residual stenosis of the target lesion
and no in-hospital DoCE).
• Device-oriented Composite Endpoints at 1 month and 6 months and annually to 3
years and its individual components. Device-oriented Composite Endpoint (DoCE)
is defined as cardiac death, MI not clearly attributable to a non- intervention
vessel, and clinically-indicated target lesion revascularization.
• Stent thrombosis according to ARC definition at all time points.
• The composite of BARC 3 or 5 bleeding at 24 months according to BARC
definition
• The individual bleeding events (BARC 1, 2, 3, 4 and 5) according to the BARC
definition
Background summary
Patients with unprotected left main coronary artery (uLMCA) lesions benefit
from revascularisation. Over the years coronary artery bypass graft (CABG)
surgery has been the preferred strategy. With improved percutaneous coronary
intervention (PCI) techniques this procedure has become extremely safe with
good long term outcomes in patients with non-complex disease. uLMCA has been a
contra indication for PCI for many years. With the introduction of stents for a
predictable acute outcome uLMCA has become feasible, but was still limited by
the frequently needed repeat procedures due to in-stent restenosis. This has
been improved with the use of drug-eluting stents (DES) and uLMCA PCI has been
accepted in the ESC guidelines for several patients groups. DES technology has
continuous been improved and several studies has demonstrated superiority of
new designs over the first generation DES.
In the previous studies using the first generation drug-eluting stent, a
significant association was observed between discontinuation of dual antiplatet
therapy and the occurrence of thrombotic events in the first 6 or 12 months.
Based on these findings, the current ESC guidelines therefore recommends 6-12
months after drug-eluting stent implantation. However, the recent randomized
trials using 2nd generation drug-eluting stent (everolimus-eluting or
zotarolimus eluting) demonstrated no benefits favouring prolonged dual
antiplatelet therapy while many shortcomings have been found with prolonged
DAPT therapy including bleeding and cost issues. In the PRODIGY study
(Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intima
Hyperplasia Study), the primary outcome (all- cause mortality, MI, or stroke)
was similar between 6 or 24 month DAPT therapy. More recently, the OPTIMIZE
trial (Optimized Duration of Clopidogrel Therapy Following Treatment With the
Zotarolimus-Eluting Stent in Real-World Clinical Practice) showed that in
patients with stable coronary artery disease or low-risk ACS treated with
zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was
non-inferior to 12 months for net clinical adverse and cerebral events, without
significantly increasing the risk of stent thrombosis. These trials suggest
that the short DAPT therapy (3 months) could be safe after implantation of 2nd
generation drug-eluting stent.
Study objective
The primary objective is to establish the non-inferiority of the Synergy stent
relative to the Xience stent for prevention of MACE. The effect measure is the
difference in the rate of MACE in patients randomized to treatment with the
Synergy ( index) stent (r1) to that in patients randomized to treatment with
the Xience (control) stent (r0). The null hypothesis is that the risk
difference (r1-r0) is larger than or equal to the specified non-inferiority
margin of 7.5%. The alternative hypothesis is that the difference in the MACE
rate is less than 7.5%. The null-hypothesis of inferiority of the Synergy stent
to the XIENCE stent will be rejected if the upper bound of 95% confidence
interval of risk difference (r1-r0) falls below 7.5%.
Study design
This is a prospective, randomized, multicenter study in patients with an
indication for coronary artery revascularisation who have been accepted for
percutaneous coronary intervention (PCI) of the left main coronary artery.
Patients who are scheduled to undergo standard PCI of the left main coronary
artery will be randomized in a 1:1 fashion to the Synergy stent arm or to
XIENCE stent arm. Dual antiplatelet therapy (DAPT) will be stopped at t=4
months in the Synergy arm whereas in the control arm DAPT will be continued for
12 months.
A subgroup of 100 patients will have control angiography with Optical Coherence
Tomography (OCT) at t=3 months after treatment.
Total clinical follow-up will be 5 years.
Intervention
Patients who are scheduled to undergo standard PCI of the left main coronary
artery will be randomized in a 1:1 fashion to the Synergy stent arm or to
XIENCE stent arm. Dual antiplatelet therapy (DAPT) will be stopped at t=4
months in the Synergy arm whereas in the control arm DAPT will be continued for
12 months.
Study burden and risks
Because this study follows normal clinical practice, there is no presumption
that there are additional disadvantages or risks for participation. The risks
of the procedures that are part of standard care are explained.
For sub-study group:
After 3 months to undergo two additional procedures, this will expose the
patient to more radiation than when a patient would not participate in this
study. This additional risk is assessed by an expert who has nothing to do with
the investigation. This has calculated that the risk is equivalent to almost 38
months of background radiation. This represents an additional risk of 1 in 2900
for fatal cancer.
Beardmore Street 1
Clydebank G81 4SA
GB
Beardmore Street 1
Clydebank G81 4SA
GB
Listed location countries
Age
Inclusion criteria
1. Patient has an indication for coronary artery revascularisation of the left main artery in accordance with the ESC guidelines
2. Patient has been discussed with the cardiac surgeon prior to PCI procedure
3. Patient is accepted for PCI
4. Patient is at least 18 years of age.
5. The patient understands and accepts the meaning and the aims of the study and is willing to provide written informed consent
6. The patient is willing to comply with specified follow-up evaluation and can be contacted by telephone.
Exclusion criteria
1. Not able to receive anti-platelet treatment due to contraindications
2. Known allergy to acetylsalicylic acid, clopidogrel, prasugrel or ticagrelor
3. Cardiogenic shock
4. STEMI within the last 5 days
5. Planned surgery within 12 months after stent introduction
6. History of bleeding diathesis or active major bleedings
7. Major surgery within previous 15 days
8. Current participation in another trial which has not yet reached its primary endpoint
9. Life expectancy < 12 months
10. Hypersensitivity or contraindication to everolimus or structurally-related compounds, cobalt, chromium, nickel, tungsten, acrylic, platinum and fluoropolymers
11. Female patient with child bearing potential not taking adequate contraceptives or currently breastfeeding
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 | NL51314.078.14 |