To demonstrate the safety and efficacy of the SELUTION SLR* 014 DEB for treatment of bare-metal or drug-eluting in-stent restenosis (ISR).
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for effectiveness is TLF rate at 12 months post-index
procedure. TLF is defined as all cardiac death, target vessel
myocardial infarction (SCAI definition), or clinically driven TLR.
Secondary outcome
Powered: Follow-up in-segment minimum lumen diameter (MLD) at 12 months
(angiographic follow-up subset).
Other:
Secondary endpoints will include:
• Device success
• Lesion success
• Procedure success
The following secondary clinical endpoints will be evaluated prior to
discharge, at 1, 6 and 12 months and annually thereafter through 5 years
follow-up:
• Composite safety endpoint: defined as any death, any MI (SCAI), or any repeat
revascularization.
• All-cause mortality
• Cardiovascular mortality
• MI (SCAI, UDMI 3/4, ARC2)
• TLR
• Target vessel revascularization (TVR)
• Target vessel failure (TVF), defined as composite of cardiac death, MI, or
TVR.
• Stent thrombosis (ST, Academic Research Consortium [ARC] definite or
probable)
• Bleeding (Bleeding Academic Research Consortium [BARC] classification)
• Patient- oriented composite defined as any death, any MI, or any repeat
revascularization
• Net adverse clinical events defined as Death, MI, TVR, ST, or Bleeding (BARC
2-5)
The following secondary angiographic and imaging endpoints will be evaluated in
the designated subsets.
• Binary angiographic restenosis
• In-stent percent diameter stenosis
• In-segment percent diameter stenosis
• In-stent late loss
• In-stent MLD
• OCT assessment of neointimal hyperplasia, neo-atherosclerosis, and stent
malapposition at 12-13 months (OCT subset)
Background summary
In-stent restenosis (ISR) is a key measure of success in percutaneous coronary
intervention (PCI) and remains a widespread therapeutic challenge.
Bare-metal stents (BMS) improved procedural results and reduced restenosis
compared with balloon angioplasty (BA), but a requirement for
repeat target lesion revascularization remained in range of 15-20% due to
neointimal hyperplasia.
the use of Drug-eluting stents (DES) resulted in a highly significant 50-75%
decrease in restenosis rates due to near elimination of neointima, however
leading to late stent thrombosis due to ongoing inflammation and absent or
delayed healing, lading to required prolonged dual antiplatelet therapy (DAPT)
and ongoing risk of restenosis.
Target Lesion Revascularization is still necessary for about 4% of patients by
one year after stenting.
Treatment with DES for in-stent restenosis creates layers of stens give risk of
uncertain healing, thrombosis, recurrent ISR and bleeding complications due to
dual antiplatelet therapy. Therefore drug-coated balloons (DCB) have re-emerged
as therapy for ISR.
DCB allow patients to avoid additional stent layers and to minimize the use of
DAPT while providing a superior treatment result to current BA.
Sirolimus is able to stop cell growth without killing the cells that line the
blood vessels. Paclitaxel is more toxic to cells lining the blood vessels,
particularly in higher doses, and it can kill some of these cells. Sirolimus
is therefore considered a safer alternative to paclitaxel.
Study objective
To demonstrate the safety and efficacy of the SELUTION SLR* 014 DEB for
treatment of bare-metal or drug-eluting in-stent restenosis (ISR).
Study design
Prospective, multi-center, single blind, randomized, controlled, noninferiority
clinical trial.
Subjects with previous bare-metal or drug-eluting coronary stent and qualifying
evidence for ISR will be screened per the protocol inclusion
and exclusion criteria to achieve a maximum of 418 randomized subjects
(includes 5% allowance for loss to follow-up). Eligible subjects
will be randomized 1:1 to treatment with either the SELUTION SLR* DEB or SOC to
include contemporary DES (zotarolimus-eluting stents
and everolimus-eluting stents only) or non-DEB BA. A maximum of 20% of
patients randomized to SOC will be treated with BA.
This is a single blind trial, meaning that the patient but not the treating
clinician will be blinded to the treatment given after randomization. The
patient will remain blinded until they reach primary endpoint at 12 months and
all protocol mandated assessments have been completed.
Intervention
Subject preparation and percutaneous access should be performed according to
standard hospital.
After confirming all clinical and target lesion inclusion and exclusion
criteria, pre-dilatation may be performed: a visually estimated residual
diameter stenosis < 30% must be achieved prior to randomization. IVUS and/or
OCT will be performed in all subjects after determining angiographic
eligibility and prior to randomization.
Prior to randomization the SOC treatment choice must be declared; either DES or
BA. If subject is randomized in the control group, they will be treated with
the pre-declared treatment: DES (otarolimus-eluting stent or an
everolimus-eluting stent) or BA.
If the subject is randomized in the study group, they will be treated with the
study SELUTION SLR* DEB.
Study burden and risks
The risks of the PTCA procedure are the same as for the study device group or
the standard of care
group.
The potential risks related to conducting PTCA procedures for the treatment of
coronary artery lesions include, but are not limited to the following:
• Allergic reaction to contrast medium, anticoagulants, and antiplatelets
• Aneurysm or pseudoaneurysm
• Arrhythmias
• Arteriovenous (AV) fistula
• Death
• Embolization
• Fever
• Hematoma
• Hemorrhage, incl. bleeding at puncture site
• Hypotension/hypertension
• Increased Procedure Time/Additional Interventions
• Ineffective Anti*Restenotic Therapy
• Inflammation
• Ischemic Heart Disease
• Myocardial Infarction
• Occlusion
• Pain or tenderness
• Hemothorax
• Renal failure
• Sepsis/infection
• Shock
• Stroke
• Thrombosis
• Vessel dissection, occlusion, perforation, recoil, restenosis, rupture, or
spasm
Potential adverse events that may be unique to the SELUTION SLR* PTCA DEB
Sirolimus drug coating or the active pharmaceutical ingredient (sirolimus)
include, but are not limited to:
• Abnormal liver function tests
• Anemia
• Arthralgias
• Diarrhea
• Hypercholesterolemia
• Hypersensitivity, including anaphylactic/anaphylactoid type reactions
• Hypertriglyceridemia
• Hypokalemia
• Interstitial lung disease
• Leukopenia
• Lymphoma and other malignancies
• Thrombocytopenia
The potential adverse events listed above are related to the oral
administration of Sirolimus at significantly higher doses than what would be
delivered by the SELUTION SLR* PTCA DEB locally to the vessel wall. Therefore,
due to the local administration and low dosage, these pharmacological
interactions are deemed possible but unlikely.
The first 60 patients who consent to participate in the imaging sub cohort will
receive angiography and OCT at 12-month follow-up.
The total exposure as a result of these imaging studies is approximately 4.4
mSv. In comparison: the background
radiation in the Netherlands is ~2.5 mSv, per year. Cumulative exposure to
radiation can increase your risk of
developing certain types of cancer in the future. The estimated additional risk
of cancer is 1 in 9,000 for these
additional procedures.
Jenner 4, Suite 180/190
Irvine CA 92618
US
Jenner 4, Suite 180/190
Irvine CA 92618
US
Listed location countries
Age
Inclusion criteria
Subjects must meet all of the following clinical criteria to participate in the
trial:
1. Subject age is >= 18 years or minimum legal age as required by local
regulations.
2. Female subjects of childbearing potential have a negative pregnancy test <= 7
days before
the procedure.
3. Subject presents with chronic coronary syndrome (CCS) (manifest as
documented angina or positive functional testing), unstable angina or
stabilized non-ST elevation MI (NSTEMI) (biomarkers stabilized or down
trending) with an indication for PCI and planned intervention.
4. Subject is eligible for DAPT treatment with aspirin plus either,
Clopidogrel, Prasugrel, or Ticagrelor. Note: Subjects who require continued
oral anticoagulant therapy may omit aspirin at discretion of investigator.
5. Life expectancy > 1 year in opinion of investigator.
6. Subject is willing and able to provide informed consent and comply with
study procedures and required follow-up evaluations.
Subjects must meet all the following imaging criteria to participate in the
trial:
1. Target lesion is within a native coronary artery or major branch.
2. Target lesion is within a previously placed BMS or DES and does not extend
further than 5 mm beyond either the proximal or distal edge of the stent.
3. Up to two (2) non-target lesions in non-target vessels may be treated, but
successful PCI of the non-target lesions must be completed before treatment of
the target lesion. Successful treatment is defined as no greater than 30%
residual stenosis by visual estimate, no dissection greater than National
Heart, Lung, Blood Institute (NHLBI) type C, and Thrombolysis in Myocardial
Infarction (TIMI) grade flow in the non-target lesion > 2.
4. Target lesion is < 26 mm in length.
5. Target lesion has diameter stenosis > 50% and <= 99% by visual estimate.
6. RVD is >= 2.00 mm and <= 4.50 mm.
7. Target lesion must be successfully pre-dilated/pre-treated. Note: Successful
pre-dilation/pre-treatment is defined as dilation or pre-treatment that
achieves stent expansion of approximately 80% of the distal RVD (at the
discretion of the investigator) based on intravascular ultrasound
(IVUS)/optical coherence tomography (OCT) and no greater than 30% residual
stenosis by visual estimate and no dissection greater than NHLBI type C. TIMI
grade flow in the target lesion must be > 2. Note: Atherectomy and cutting
balloon are permitted for pre-treatment.
Exclusion criteria
Clinical exclusion criteria:
1.Known hypersensitivity or allergy to Sirolimus or other pharmacologic agents
required for the procedure.
2. STEMI within 30 days.
3. Planned treatment of additional lesions in the target vessel, or more than
two (2) non-target lesions within non-target vessels, during the index
procedure.
4. Target lesion is located within a bifurcation with planned treatment of side
branch vessel.
5. Target lesion is the more than 3rd or greater stent failure (i.e., more than
two [2] layers of
stent are present at any segment of the target lesion).
6. Target vessel had any previous vascular brachytherapy treatment or is
planned to undergo brachytherapy at index procedure.
7. Previous PCI of the target vessel within 30 days.
8. Planned PCI of a non-target vessel, or a non-target lesion in the target
vessel, within 30 days of randomization.
9. Subject has chronic renal insufficiency (dialysis dependent, or glomerular
filtration rate [GFR] <= 30 ml/min/1.73 m2 within 30 days of index procedure) or
has undergone renal transplantation.
10. Subject has acute renal insufficiency confirmed by 50% increase of serum
creatinine within 48 hours before procedure and/or decrease in urine output.
11. History of active peptic ulcer or gastrointestinal bleeding within prior 6
months or other inability to comply with the recommended duration of DAPT.
12. Subject is pregnant, breast-feeding, or a woman of childbearing potential
who is not using appropriate contraceptives to avoid becoming pregnant.
13. Documented left ventricular ejection fraction (LVEF) < 25%.
14. Currently participating in another investigational drug or device study
that has not completed primary endpoint follow-up.
Imaging exclusion criteria:
1. Target lesion is total occlusion or has evidence of thrombus.
2. Target lesion involves an unprotected left main.
3. Target lesion has > 30% residual stenosis by visual estimate or dissection
greater than NHLBI type C after pre-dilation/pre-treatment.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | NCT04280029 |
| CCMO | NL71862.018.19 |