The primary objective is to demonstrate the safety and efficacy of the BuMA DES in patients with functionally significant ischemia requiring percutaneous coronary intervention (PCI) with implantation of drug eluting stents for the treatment of…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Target lesion failure at 12 months.
Target lesion failure (TLF) is defined as the composite of cardiac death,
target vessel-related myocardial infarction (TV-MI), and clinically-driven
target lesion revascularization (TLR).
Secondary outcome
All secondary endpoints will be compared in the BuMA DES group versus the DP
EES group. All endpoints will be evaluated in-hospital and at 30 days, 6
months, 12 months, and 2, 3, 4, and 5 years unless specified otherwise.
Powered Secondary Endpoint
Long-term Safety and Efficacy, defined as target lesion failure (TLF) between
12 months and 5 years by landmark analysis. TLF is defined as the composite of
cardiac death, target vessel-related myocardial infarction (TV-MI), and
clinically-driven target lesion revascularization (TLR).
Secondary Safety Endpoints
1. Major adverse cardiac events (MACE), defined as a composite of all-cause
death, myocardial infarction, and target vessel revascularization
2. Mortality, classified as cardiac or non-cardiac, and reported cumulatively
and individually
3. Myocardial infarction (MI), defined according to the modified Third
Universal Definition
4. Stent thrombosis, definite or probable (ARC-defined), classified as early,
late, or very late
5. Bleeding complications (BARC definitions), evaluated as components and as a
composite of BARC Type 3 and 5 bleeding
Secondary Efficacy Endpoints
1. Lesion success, defined as attainment of <30% residual stenosis, as measured
by quantitative coronary angiography (QCA) using any percutaneous method
[evaluated post-procedure]
2. Device success, defined as attainment of <30% residual stenosis of the
target lesion measured by QCA using the assigned device [evaluated
post-procedure]
3. Procedure success, defined as lesion success without the occurrence of
in-hospital MACE [evaluated in-hospital]
4. Clinically-driven target lesion revascularization (TLR) [evaluated
in-hospital and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years]
5. Clinically-driven target vessel revascularization (TVR) [evaluated
in-hospital and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years]
6. Target vessel failure (TVF), defined as cardiac death, target vessel-related
MI, or clinically-driven target vessel revascularization [evaluated in-hospital
and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years]
7. Target Lesion Failure (TLF), defined as cardiac death, target vessel-related
MI, or clinically-driven target lesion revascularization [evaluated in-hospital
and at 30 days, 6 months, and 2, 3, 4, and 5 years]
Background summary
Percutaneous coronary intervention (PCI) with drug eluting stents (DES) is a
mainstay of treatment for
patients with coronary artery disease (CAD), including stable angina, silent
ischemia, and acute coronary
syndromes (ACS).1, 3-5 Compared with bare metal stents (BMS), DES reduce
restenosis and the
consequent need for repeat revascularization via the inhibition of neointimal
hyperplasia.6 However, even
with the use of DES repeat intervention is required in >10% of all patients
within 1 year,7 and DES use
has been associated with a small incremental risk of late (>30 days to 1 year
post-implantation) and very
late (>1 year post-implantation) stent thrombosis. Although rare, stent
thrombosis is a devastating
complication, usually associated with myocardial infarction or death.8 Extended
duration dual antiplatelet
therapy (DAPT) is required after DES implantation, with an attendant risk of
bleeding complications;2
however, the risk of stent thrombosis persists following DAPT discontinuation.9
DES are also associated with delayed vascular healing, as evidenced by
histologic data from autopsy
studies of stent thrombosis that reveal persistent fibrin deposition and poor
re-endothelialization.10, 11
While the mechanisms by which DES cause a prolongation of arterial healing are
incompletely
understood, the permanent presence of a non-erodable polymer drug release
matrix is thought to be a
contributor to both late stent thrombosis and late restenosis.12 The polymer
has also been implicated in
localized hypersensitivity reactions and adverse late vessel wall
remodeling.13, 14 Although secondgeneration
DES with more biocompatible polymers and reduced strut dimensions have improved
the
extent of endothelialization, concerns regarding late stent thrombosis and
delayed vascular healing
remain,15 and a persistent inflammatory response continues to be observed.16, 17
To address the issue of permanent polymer as a contributor to inflammation,
stent thrombosis, and
restenosis, DES using erodible polymers for drug delivery have been developed.
Long-term follow-up
has demonstrated that this technology is capable of reducing (but not
eliminating) the occurrence of very
late stent thrombosis; however, major adverse cardiac event rates are
comparable to those observed
with durable polymer DES.18, 19 In addition, limitations remain in the
implementation of erodible polymers
in currently available DES. The polymer composition required for biodegradation
conflicts with the optimal
adhesive and mechanical properties of balloon-expandable coronary stent
coatings, creating the
potential for cracking and delamination upon stent placement and over time as
the polymer degrades;
these effects may impair re-endothelialization and serve as a substrate for the
observed thrombosis and
inflammation.20, 21 Furthermore, optimization of the timeframes for drug
elution and polymer resorption
have the potential to improve early vascular healing and thereby reduce
long-term adverse events.22
For these reasons, the development of new-generation DES that incorporate
erodible polymers to
prevent restenosis, while improving the speed and completeness of
re-endothelialization and restoration
of normal vascular function, is desirable to improve the outcomes of patients
undergoing PCI for the
treatment of CAD.
Study objective
The primary objective is to demonstrate the safety and efficacy of the BuMA DES
in patients with functionally significant ischemia requiring percutaneous
coronary intervention (PCI) with implantation of drug eluting stents for the
treatment of stable coronary artery disease or acute coronary syndromes without
ST-segment elevation (unstable angina [UA] and non-ST-segment elevation
myocardial infarction [NSTEMI]) by randomized comparison with
commercially-available durable polymer everolimus-eluting stent systems.
Study design
This prospective, multicenter study will enroll up to 1632 subjects at up to
130 investigational sites in North America, Japan, and Europe. Patients
presenting with symptomatic ischemic heart disease (including chronic stable
angina with evidence of ischemia, unstable angina, or non-ST segment elevation
myocardial infarction) who require elective or urgent percutaneous coronary
intervention (PCI) to treat up to 3 native coronary artery lesions in up to 2
major coronary arteries, in vessel diameters of >=2.25 mm to <=3.50 mm and lesion
lengths <=31 mm, and who meet all eligibility criteria will be enrolled in the
study and randomized 2:1 (stratified by presentation [acute coronary syndrome
vs. non-ACS], diabetes status [with vs. without medically-treated diabetes
mellitus], and study site) to the following treatment groups:
Intervention: Coronary revascularization with the BuMA SupremeTM Biodegradable
Drug Coated Coronary Stent System (BuMA DES).
Control: Coronary revascularization with commercially-available durable polymer
everolimus-eluting stent systems (DP EES).
Subjects will have clinical follow-up in-hospital and at 30 days, 6 months, 12
months, and 2, 3, 4, and 5 years. Follow-up at 30 days and 12 months will be
clinic visits, while the 6-month follow-up and annual follow-up at 2-5 years
will be via telephone contact (or optional clinic visit). Subjects in whom no
study stent is implanted will be followed to 12 months only.
Intervention
Intervention: Coronary revascularization with the BuMA SupremeTM Biodegradable
Drug Coated Coronary Stent System (BuMA DES).
Control: Coronary revascularization with commercially-available durable polymer
everolimus-eluting stent systems (DP EES).
Study burden and risks
Refer to Section 9.0 of the PIONEER III Trial Clinical Investigation Plan v4.0
and Section 6.0 of the ICF for full details of the risk for human subjects.
Enrollment in the trial involves exposure to some risks. The risks of trial
participation are not expected to be materially different from those
encountered by an individual undergoing PCI with DES outside the context of the
trial (§8.9). The use of the BuMA DES may pose additional potential risks of an
unknown nature or frequency.
The clinical investigation plan is specifically designed to manage and minimize
risks through careful subject selection, thorough training of investigators,
adherence to pre-determined time points to assess subject clinical status, and
regular clinical monitoring visits by Sponsor-appointed monitoring personnel.
In addition, an independent Data Safety Monitoring Committee will meet
regularly throughout the trial to monitor the safety of subjects.
2nd Floor, TEDA BioPharm Res, Building B #5 4th St, TEDA
Tianjin 300457
CN
2nd Floor, TEDA BioPharm Res, Building B #5 4th St, TEDA
Tianjin 300457
CN
Listed location countries
Age
Inclusion criteria
Potential subjects must meet ALL of the following criteria to be eligible for
inclusion in
the study:
General Inclusion Criteria
1. The patient is a male or non-pregnant female >=20 years of age and not
greater than 99 years of age
2. The patient has symptomatic ischemic heart disease, including chronic stable
angina (and/or objective evidence of myocardial ischemia on functional study or
invasive fractional flow reserve [FFR] measurement) or acute coronary
syndromes (UA or NSTEMI), that requires elective or urgent percutaneous
coronary intervention (PCI).
3. The patient is an acceptable candidate for percutaneous coronary intervention
(PCI) with drug-eluting stents, and for emergent coronary bypass graft (CABG)
surgery
4. The patient is willing to comply with specified follow-up evaluations
5. The patient or legally authorized representative has been informed of the
nature
of the study, agrees to its provisions, and has been provided written informed
consent approved by the appropriate Institutional Review Board (IRB) or Ethics
Committee (EC), Angiographic Inclusion Criteria
1. Target vessel(s) must be major coronary artery or branch vessels with a
visually estimated reference diameter of >=2.25 mm to <=3.50 mm. Treatment is
limited to a maximum of 2 target vessels per subject, a maximum of 2 target
lesions per epicardial vessel, and a maximum of 3 target lesions per subject.
2. Target lesion(s) must be de novo or previously unstented restenotic native
coronary artery lesions (no in-stent restenotic lesions permitted)
3. Target lesion(s) must have a visually estimated diameter stenosis of >50% and
<100%
4. Target lesion(s) must measure 31 mm or less in length by visual estimation,
and must be treatable with a single study stent
5. In subjects in whom treatment of 2 target lesions in a single epicardial
vessel is planned, there must be adequate separation between lesions to ensure
a gap of >=10 mm between study stents
Exclusion criteria
Potential subjects will be excluded if ANY of the following conditions apply:
General Exclusion Criteria
1. Pregnant or nursing patients and those who plan pregnancy in the period up to
1 year following index procedure. Female patients of childbearing potential
must have a negative pregnancy test done within 7 days prior to index
procedure per site standard test.
2. Patients with a history of bleeding diathesis or coagulopathy,
contraindications
to anti-platelet and/or anticoagulant therapy, or who will refuse transfusion
3. Patients who are receiving or will require chronic anticoagulation therapy
for
any reason
4. Known hypersensitivity or contraindication to aspirin, heparin/bivalirudin,
ADP
receptor antagonists (clopidogrel, prasugrel, ticagrelor, ticlopidine), cobalt
chromium, 316L stainless steel or platinum, sirolimus or its analogues, and/or
contrast sensitivity that cannot be adequately pre-medicated
5. ST-segment elevation myocardial infarction (STEMI) at index presentation or
within 7 days prior to randomization
6. Known LVEF <30% or cardiogenic shock requiring pressors or mechanical
circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist
device, other temporary cardiac support blood pump)
7. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR)
<30
mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation or
Cockcroft-Gault formula) or dialysis at the time of screening
8. Target vessel percutaneous coronary intervention with stent placement in the
previous 3 months
9. Planned elective surgery that would require discontinuation of DAPT within 6
months of the index procedure
10. Past or pending heart or any other organ transplant, or on the waiting list
for
any organ transplant
11. Patients who are receiving immunosuppressant therapy, or who have known
immunosuppressive or severe autoimmune disease that will require chronic
immunosuppressive therapy. NOTE: Corticosteroid use is permitted.
12. Known other medical illness or known history of substance abuse that may
cause non-compliance with the protocol or prescribed medications, confound data
interpretation, or is associated with a life expectancy of less than 1 year
13. Current participation in another investigational drug or device study,
Angiographic Exclusion Criteria
1. Target lesion contains a total occlusion (TIMI 0 flow)
2. Target lesion is in an unprotected left main coronary artery location
3. Target lesion is located within an arterial or saphenous vein graft or graft
anastomosis, or in a native artery location that requires traversal of an
arterial or saphenous vein graft to access
4. Target lesion involves a previously stented segment (in-stent restenosis) or
is
<=10 mm from a previously implanted stent
5. Target lesion involves a bifurcation in which 2-vessel stenting is planned
6. Index procedure treatment plan for the target lesion includes stent
overlapping
7. Index procedure treatment plan for the target vessel includes treatment of 2
target lesions that would result in 2 study stents placed <10 mm apart
8. Index procedure treatment plan for the target vessel includes vessel
preparation other than balloon pre-dilatation (e.g., cutting balloon,
atherectomy, thrombectomy, excimer laser angioplasty, brachytherapy)
9. Treatment plan includes repeat intervention (staged procedure)
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 | NCT03168776 |
| CCMO | NL63692.101.17 |