To compare in diabetic patients eligible for percutaneous coronary intervention (PCI) with minimal exclusion criteria, the efficacy and safety of Abluminus/Abluminus DES+ sirolimus-eluting stents (SES) versus XIENCE Everolimus-Eluting Stents (EES).…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Glucose metabolism disorders (incl diabetes mellitus)
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Primary:
o Ischemia-driven Target Lesion Revascularization (idTLR) at 1-year Follow-Up
(powered for non-inferiority and sequentially superiority).
o Target lesion failure (TLF - composite of cardiovascular death, target vessel
myocardial infarction [MI], or ischemia driven target lesion
revascularization) at 1-year FU, powered for non-inferiority
Secondary outcome
-- Secondary:
1) Safety composite endpoint of the occurrence of cardiovascular death and
target-vessel myocardial infarction (MI) at 1 year (non-inferiority).
2) In case the co-primary TLR endpoint (TLR for non-inferiority) will be
demonstrated at 1 year, then the occurrence of idTLR at 2-year FU will
be evaluated (efficacy endpoint - superiority).
3) In case the co-primary TLF endpoint (TLF for non-inferiority) will be
demonstrated at 1 year, then the occurrence of the composite of cardiovascular
death, target vessel MI and idTLR (TLF) at 1-year FU will be evaluated (safety
endpoint - superiority).
4) Bleeding BARC 2 or greater
- Others:
* Composite of cardiovascular death, target vessel MI and idTLR (TLF) at 2
years.
* Occurrence of cardiovascular death and target-vessel myocardial infarction
(MI) at 2 years.
* All-cause mortality up to 2 years from procedure.
* Stroke up to 2 years from procedure.
* Stent thrombosis (defined for grade and timing according to the Academic
Research Consortium2).
* Technical success.
* Clinical procedural success.
* Occurrence of idTLR at 2-year FU.
* Target vessel revascularization (TVR) up to 2 years.
Background summary
Diabetes mellitus (DM) is a growing global public health problem. Some 415
million people worldwide or one in eleven adults are estimated to have DM. If
the current trend in diabetes prevalence continues, by 2040 some 642 million
people, or one adult in ten, will have diabetes.
Patients with DM are more affected by coronary artery disease and when treated
by coronary angioplasty with stent implantation they remain at higher risk for
in-stent restenosis and adverse cardiovascular events even in the drug-eluting
stent (DES) era.
The presence of DM (particularly insulin-treated DM) has been a consistent,
independent predictor of in-stent restenosis in most stent trials and
registries. First-generation drug-eluting stents (DESs) reduced the need for
repeat revascularization with a similar safety profile when compared with
bare-metal stents.
Data from several direct randomized comparisons, registries, and meta-analyses
of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in
diabetics have been reported. In all of these studies have been significantly
underpowered to define whether there are true differences in clinical safety or
efficacy between SES and PES in diabetic patients.
Furthermore, PCI, using the second-generation everolimus-eluting stent (EES),
has been shown to result in better long-term outcomes than when
first-generation DES are used in all-comer populations.
Although sirolimus and everolimus-eluting stents have been suggested to be less
efficacious than PES in diabetic patients, the data have been conflicting.
The benefits of EES compared to PES in reducing clinical and angiographic
restenosis were present in most subgroups in the SPIRIT trials (although
underpowered for subgroup analysis). However, among 337 patients with diabetes
randomized in SPIRIT II and SPIRIT III trials, EES compared to PES resulted in
non-significant differences in the 1-year proportions of TLR (despite a
significant reduction in late loss), whereas both late loss and TLR were
markedly reduced with EES in 886 patients without diabetes. Similarly, in the
SPIRIT IV randomized trial, EES compared with PES provided similar clinical
outcomes in diabetic patients with no difference in terms of TLF between the
two groups.
In this study, the included patients will present diabetes mellitus and are
scheduled to undergo a coronary angioplasty for one or more narrowing(s) in the
coronary arteries. Once included, the patients will receive either
Abluminus/Abluminus DES+ sirolimus-eluting stents (SES) or Everolimus-Eluting
Stents (EES) and will be followed for two years.
The purpose of the study is to compare in diabetic patients the efficacy and
safety of these two drug-eluting stents used for coronary artery narrowing
treatment.
Study objective
To compare in diabetic patients eligible for percutaneous coronary intervention
(PCI) with minimal exclusion criteria, the efficacy and safety of
Abluminus/Abluminus DES+ sirolimus-eluting stents (SES) versus XIENCE
Everolimus-Eluting Stents (EES). At least 40% of patients are expected to be
affected by multivessel coronary artery disease and 30% with the acute coronary
syndrome.
Study design
Prospective, multicenter, multinational, randomized, open label, 2-arm parallel
groups
Intervention
The included patients will undergo a Percutaneous coronary intervention (PCI)
with either Abluminus/Abluminus DES+ sirolimus-eluting stents (SES) or
Everolimus-Eluting Stents (EES).
Study burden and risks
Implantation of one of the study devices as it has been specially designed for
diabetic patients may result in improved cardiovascular function and improved
further quality of life in patients (Lower chance of restenosis in the long
term, lower chance of hospitalisation due to cardiac disease in the long term,
lower chance of chest pain). These benefits can however not been guaranteed.
Generally, all patients will receive a higher degree of telephone and clinical
follow-up than he/she would outside of the
study environment and have a dedicated clinical study team following his/her
progress.
It is hoped that through this study, information gained on the safety and
efficacy of the devices used will help in the
management of future patients with similar conditions
Potential adverse events which may be associated with the implantation of a
coronary stent in a native coronary artery include those risks associated with
percutaneous transluminal coronary angioplasty as well as additional risks
related to the use of the stent.
As with any treatment of narrowing of one or more coronary artery lesions, the
major complications are:
•Death: less than 1%
•Stroke: 0.5%
•Heart Attack: 2-5%
•Bleeding (major and minor): 2-5%
•The risk of a blockage of the stent(s), called stent thrombosis and the
potential risk of heart attack or death due to
this blockage is less than 5% within 1 year after implantation.
The doctors performing angioplasties use X-rays to direct the stent to the
correct position. No additional radiation will
be used in the study and patients' exposure to the radiation will be part of
the normal care and should carry no extra
risks. High doses of x-ray have the potential to cause skin damage, however, we
do not anticipate this angioplasty
will exceed the accepted threshold.
5600 Mariner St. STE 200
Tampa FL 33609-3417
US
5600 Mariner St. STE 200
Tampa FL 33609-3417
US
Listed location countries
Age
Inclusion criteria
Inclusion criteria: Clinical Inclusion Criteria 1. Patient understands the
trial requirements and the treatment procedures and provides written informed
consent; 2. Age >= 18 years (>= 19 years of age for South Korea and >= 21 years of
age for Singapore); 3. Diabetic patients: either: a. Patient with a previous
documented diagnosis of diabetes mellitus (Type 1 or Type 2) and currently
undergoing pharmacological treatment (oral hypoglycemic agents or insulin) b.
Newly diagnosed diabetes: either: i. Fasting plasma glucose (FPG) >=126 mg/dL
(7.0 mmol/L). Fasting is defined as no caloric intake for >=8 hours or ii.
Two-hour plasma glucose >=200 mg/dL (11.1 mmol/L) following a 75g oral glucose
tolerance test or iii. HbA1c level >= 7% (53 mmol/mol) Patients who are newly
diagnosed are included even if they are not on pharmacological treatment (oral
hypoglycemic agents or insulin) 4. Symptomatic coronary artery disease
including chronic stable angina, silent ischemia, and non-ST-segment elevation
acute coronary syndrome (NSTE-ACS) 5. Patient is eligible for percutaneous
coronary intervention (PCI); Previous PCI (with balloon angioplasty or
stenting) is allowed if performed >12 months before index procedure; 6.
Patient is willing and able to comply with all protocol-required follow-up
evaluations. Angiographic Inclusion Criteria (visual estimate) 7.Presence of >=1
de novo coronary artery stenosis >50% in a native coronary artery which can
be treated with a stent ranging in diameter from 2.25 to 4.0 mm and can be
covered with 1 or multiple stents; and 8. No limitation to the number of
treated lesions, number of vessels, or lesion length if the patient is judged
eligible for PCI by the treating physician according to the local standard of
care.
Exclusion criteria
Exclusion criteria: Clinical Exclusion Criteria: 1. Patient lacking capacity
(i.e. patient suffering from dementia and others) to provide informed consent
2. Patients in cardiogenic shock as defined in appendix A; 3. Patient has known
allergy to the study stent system or protocol-required concomitant medications
(e.g. aspirin, clopidogrel, prasugrel, ticagrelor, heparin, stainless steel,
cobalt, chromium, sirolimus, everolimus, radiographic contrast material) that
cannot be adequately pre-medicated; 4. Planned surgery (cardiac and
non-cardiac) within 6 months after the index procedure unless the
dual-antiplatelet therapy (DAPT) can be maintained throughout the peri-surgical
period; 5.Patients undergoing primary percutaneous coronary intervention for
ST-segment elevation myocardial infarction (STEMI) 6. Patient is pregnant,
nursing, or is a woman of child-bearing potential who is not surgically
sterile, < 2 years postmenopausal, or does not consistently use effective
methods of contraception; 7. Patient has any other serious medical illness
(e.g., cancer, end-stage congestive heart failure) that may reduce life
expectancy to less than 12 months; 8. Acute or chronic renal dysfunction (serum
creatinine >3.0 mg/dl); 9. Currently participating in another
investigational drug or device study. Angiographic Exclusion Criteria: 10.
In-stent restenotic lesions; 11. Lesions involving venous or arterial bypass
grafts.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | NCT04236609 |
| CCMO | NL72858.018.20 |