The study aims to assess the safety and efficacy of the Freesolve scaffold in de novo coronary artery lesions compared to the Xience coronary stent system during standarfd clinical use. This is in the context of the MDR and the legal obligation to…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Target Lesion Failure (TLF) at 12 months, a composite of Cardiac Death, Target
Vessel Q-wave or non-Q wave MI, and clinically driven Target Lesion
Revascularization (TLR).
see also CIP section 7.7
Secondary outcome
* Safety Objective: Cardiac death at 1, 6, 12, 24, 36, 48 and 60 months; target
vessel MI (TV-MI) at 6, 12, 24, 36, 48 and 60 months; definite/probable
scaffold thrombosis at 1, 6, 12, 24, 36, 48 and 60 months;
*Performance Objective: clinically driven TLR at 1, 6, 12, 24, 36, 48 and 60
months; procedure success.
* A powered secondary endpoint analysis in the diabetic population will be
performed to support a diabetic indication for Freesolve.
* A powered secondary endpoint analysis evaluating cumulative TLF rates between
1- and 5-years post-procedure will be performed.
* TLF, composite of Cardiac Death, Target Vessel Q-wave or non-Q wave MI, and
clinically driven TLR at 1, 6, 12, 24, 36, 48 and 60 months.
* TVF, a composite of Cardiac Death, Target Vessel Q-wave or non-Q wave MI, and
clinically driven Target Vessel Revascularization (TVR) at 1, 6, 12, 24, 36, 48
and 60 months.
* Cardiac death at 1, 6, 12, 24, 36, 48 and 60 months.
* Cardiovascular death at 1, 6, 12, 24, 36, 48 and 60 months.
* All-cause mortality at 1, 6, 12, 24, 36, 48 and 60 months.
* Target vessel MI in accordance to protocol defined peri-procedural MI and 3rd
universal definitions for non-periprocedural MI at 1, 6, 12, 24, 36, 48 and 60
months.
* Any MI (including non-target vessel territory) at 1, 6, 12, 24, 36, 48 and 60
months.
* Clinically driven TLR at 1, 6, 12, 24, 36, 48 and 60 months.
* Clinically driven TVR at 1, 6, 12, 24, 36, 48 and 60 months.
* Definite or probable scaffold thrombosis rate at 1, 6, 12, 24, 36, 48 and 60
months (according to ARC-2 definition).
* Procedure success defined as achievement of < 30% final residual diameter
stenosis (by Quantitative Coronary Angiography (QCA) or visual estimation of
the target lesion, without the occurrence of cardiac death, Q-wave or
non-Q-wave MI, or repeat revascularization of the target lesion during the
hospital stay.
* Device Success defined as a final residual diameter stenosis of <30% by QCA
or visual estimation using the assigned device only with:
- successful delivery of the device to the target lesion site in the coronary
artery and
- appropriate device deployment and
- successful removal of the delivery system
see also CIP section 7.8
Background summary
Standard of care treatment of coronary artery disease with drug-eluting stents
(DES:Drug Eluting Stents) delivers good clinical outcomes with low target
lesion failure (TLF) and stent thrombosis rates. Nevertheless, the use of DES
presents some limitations, mainly due to the permanent presence of foreign
material (metal) in the vessel wall. In particular, there is a long-term risk
of stent failure, thrombosis, chronic inflammation due to the metal or polymer
components and neoatherosclerosis. Moreover the metal cage can impair the
vessel geometry, access and flow into side branches and can inhibit normal
vasomotor function, which may hinder compensatory positive re-modelling and
limits use of imaging and future treatment options. Bioresorbable scaffolds
(BRS) were developed to overcome these problems, enabling vessel restoration
and reducing long term risks. BRS are meant to provide a temporary drug eluting
scaffold, which supports the vessel after implantation, limiting acute recoil
and negative re-modelling, and enables a natural biologic reconstruction of the
arterial wall and restoration of the vascular function once the scaffold is
resorbed.
The ability of scaffolds to meet these expectations, however, have been partly
questioned by suboptimal results of the Absorb Bioresorbable Vascular Scaffold
(BVS) (Abbott Vascular, Santa Clara, CA) showing higher incidence of scaffold
thrombosis and target vessel-related myocardial infarction. Notably, while
Absorb BVS consists solely of a poly-L-lactic acid (PLLA) polymer which resorbs
over a period of more than 24 months, other scaffolds have different materials
and designs. In particular, the Magmaris (here after referred to also as DREAMS
2G= 2nd generation) consists of a magnesium (Mg) alloy which resorbs in
approximately 12 months. Data from clinical trials thus far have demonstrated
the clinical safety and performance of Magmaris and have not shown the same
safety concerns as Absorb. DREAMS 2G gained CE-Mark in 2016 and since then is
marketed as Magmaris.
Despite these positive results, iterative improvement of Magmaris to enhance
performance and usability led to the development of the 3rd generation
scaffold, DREAMS 3G (here after referred to also as Freesolve®
Sirolimus-Eluting Coronary Resorbable Magnesium Scaffold (RMS) System). This
scaffold is built with a refined magnesium alloy and enhances some scaffold
properties, such as radial strength, scaffolding time and marker visibility,
broadens the size range and reduces crossing profile and strut thickness. All
these changes are meant to improve overall clinical outcomes. The Dreams 3G
(Freesolve scaffold) obatained CE-mark in February 2024.
In order to demonstrate the safety and efficacy of Freesolve with respect to
the current state of the art devices for treatment of coronary artery disease,
drug eluting stents, a head-to-head comparison of Freesolve with the Xience DES
will be performed in the BIOMAG-II randomized controlled trial.
This is to comply with the current regulation for medical devices (MDR) for the
collection of Post Market Clinical Follow Up (PMCF) data.
Study objective
The study aims to assess the safety and efficacy of the Freesolve scaffold in
de novo coronary artery lesions compared to the Xience coronary stent system
during standarfd clinical use. This is in the context of the MDR and the legal
obligation to collect PMCF data.
Study design
A prospective, international, multi-center, randomized controlled,
non-inferiority trial.
Intervention
Percutaneous coronary intervention (PCI) with either the Freesolve or the
Xience stent.
Study burden and risks
As with any subjects undergoing percutaneous coronary intervention, subjects
may experience adverse events and/or outcomes that are listed in the IFU and
are not expected to differ from other contemporary drug eluting stent
implantation procedures.
Potential adverse events related to the oral administration of sirolimus
include, but are not limited to, abnormal liver function tests, anemia,
arthralgia, diarrhea, hypercholesterolemia, hypersensitivity (including
anaphylactic/ anaphylactoid type reactions), hypertriglyceridemia, hypokalemia,
infections, interstitial lung disease, thrombocytopenia, leukopenia, lymphoma,
and other malignancies. Since these events have been observed after oral
systemic administration of sirolimus, it is deemed extremely unlikely that they
could occur after sirolimus-eluting scaffold implantation, even if they cannot
be ruled out completely. Current literature gives no indication that these
adverse events ever occurred specifically as a result of sirolimus-eluting
stent/scaffold implantation. None of them were reported for DREAMS 3G in
BIOMAG-I. Appropriate contraindications and warnings are included in the IFU
provided with the study device.
In summary (see also CIP section 6, tabel 6), the device- and procedure-related
adverse events/ side-effects identified in clinical data of DREAMS 3G are
within the range of similar and benchmark devices or single occurrences.
Therefore, the identified adverse events/ side-effects are deemed acceptable
and do not have a negative impact on the benefit-risk ratio. No previously
unknown side-effects were identified during the clinical evaluation of DREAMS
3G and risks were consistent across the intended patient population of DREAMS
3G.
Takenhofplein 3
Nijmegen 6538SZ
NL
Takenhofplein 3
Nijmegen 6538SZ
NL
Listed location countries
Age
Inclusion criteria
See CIP section 7.12.
1. Subject is >=18 years and <= 80 years old.
2. Written informed consent provided by subject before any study related
procedure.
3. Subject is elegible for PCI according to current applicable guidelines.
4. Subject is an acceptable candidate for coronary artery bypass surgery.
5. Subjects with stable or unstable angina pectoris, documented silent
ischemia/abnormal physiologic testing or hemodynamically stable non-ST
elevation myocardial infarction (NSTEMI) patients without angiographic evidence
of thrombus at target lesion.
Note: STEMI patients may be eligible for the study for treatment of selected
non-culprit lesions, if:
* Subject and target lesion(s) meet all inclusion and no exclusion criteria and
consent occurs at least >= 72 hours after successful treatment of the culprit
lesion causing STEMI.
* Subject is hemodynamically stable with documented declining cardiac
biomarkers.
* Target lesion(s) to be treated are not located in the culprit vessel(s) and
are not culprit lesion(s).
6. Subject is elegible for DAPT therapy for at least 6-months.
7. Documented left ventricular ejection fraction (LVEF) >= 30% within 6 months
prior to or during the procedure.
8. Subject is willing and able to comply with protocol requirements, including
completion of study visits for the duration of the study.
Angiographic inclusion criteria:
1. Subjects with a maximum of two single de novo target lesions each in
separate native coronary arteries.
2. Target vessel must have a reference vessel diameter between 2.5-4.2mm by
visual estimation (may be assisted by QCA, IVUS or OCT).
3. Target lesion must be <= 28 mm in length by visual estimation (may be
assisted by QCA, IVUS or OCT) (or < 20 mm for target lesion(s) to be treated
with a study device < 3.0 mm in diameter) and must be amenable to treatment
with a single study device.
Target lesion stenosis >= 50% and < 100% by visual estimation (may be assisted
by QCA, IVUS or OCT).
4. Target lesion stenosis >= 50% and < 100% by visual estimation (may be
assisted by QCA, IVUS or OCT). Target lesion stenosis < 70% by visual
estimation, should have clinical justification for treatment as per local
standards.
5. Target lesion must have a Thrombolysis In Myocardial Infarction (TIMI) flow
>=1.
Exclusion criteria
See CIP section 7.13
1. Subject is pregnant and/or breastfeeding or intends to become pregnant
during the duration of the study.
2. Subject has clinical symptoms and/or electrocardiogram (ECG) changes
consistent with STEMI < 72 hours prior to the index procedure. Note:
Hemodynamically stable non-STEMI (NSTEMI) subjects are eligible for study
enrollment.
3. Subject has undergone prior PCI within the target vessel during the last 12
months prior to the index procedure or prior PCI within a non-target vessel <
72 hours prior to the index procedure if successful and uncomplicated.
4. Subject is on dialysis or with impaired renal function (serum creatinine >
2.5 mg/dl or 221 µmol/L, determined within 72 hours prior to the index
procedure).
5. known allergy to contrast medium, aspirin, P2Y12 inhibitors, heparin,
bivalirudin, sirolimus, everolimus, poly L-lactide, the scaffold material
(magnesium, aluminium, tantalum), or Xience stent material (cobalt, chromium,
tungsten, nickel, methacrylic polymer, and fluoropolymer).
6. Subject is receiving oral or intravenous immunosuppressive therapy (inhaled
steroids are permitted) or has known life-limiting immunosuppressive or
autoimmune disease (e.g., human immunodeficiency virus, systemic lupus
erythematosus; diabetes mellitus is permitted).
7. Life expectancy less than 1 year.
8. Planned surgery or dental surgical procedure within 6 months after index
procedure, unless DAPT can be maintained.
9. In the investigator*s opinion subject will not be able to comply with the
follow-up requirements.
10. Subjects under oral anticoagulation therapy (OAC) prior to index procedure
unless DAPT + OAC (i.e. triple therapy) can be maintained for a minimum of 1
month.
11. Subject has had a stroke or transient ischemic attack (TIA) within 6 months
prior to the index procedure.
12. Subject with active bleeding disorders, active coagulopathy, or any other
reason, who is ineligible for DAPT.
13. Subject is currently participating or plans to participate in another study
with an investigational device or an investigational drug.
Angiographic exclusion criteria
1. Target vessel has been previously treated and the target lesion is within 5
mm proximal or distal to the previously treated lesion.
2. Left main coronary artery disease.
3. Target lesion was totally occluded (100% stenosis).
4. Thrombus in target vessel.
5. Future planned staged PCI either in target or non-target vessel.
6. Ostial target lesion within the left descending (LAD), left circumflex
(LCx), or right coronary artery (within 5.0 mm of vessel origin).
7. Target lesion involves a side branch >= 2.0 mm in diameter that requires a
two-device strategy after pre-dilatation.
8. Target lesion is located in or supplied by an arterial or venous bypass
graft.
9. Target lesion with excessive tortuosity proximal to or within the lesion
based on visual estimation or heavily calcified target lesion which cannot be
adequately pre-dilated by a non-compliant and/or cutting/scoring balloon as
described in angiographic exclusion criteria 10.
10. The target lesion requires treatment with the device other than the
non-compliant balloon and/or cutting/scoring balloon prior to scaffold/stent
placement (including but not limited to atherectomy devices, intravascular
lithotripsy, drug-coated balloons etc.)
11. Target vessel was treated with brachytherapy any time prior to the index
procedure.
12. Unsuccessful pre-dilatation, defined as residual stenosis > 20% (by visual
estimation) and / or angiographic complications (e.g. distal embolization, side
branch closure, flow-limiting dissections)
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 | NCT05540223 |
| CCMO | NL86352.100.24 |