Coronary Artery Disease
Conditions
Keywords
CAD, DCB, DEB, NSTEMI, Stable Angina, Chronic Coronary Syndrome, CCS, Drug Coated Balloons, Drug Eluting Balloons, Small Vessels, SELUTIONSLR, Sirolimus
Brief summary
Prospective, randomized controlled, single-blind, multicenter, clinical trial to demonstrate the safety and efficacy of the SELUTION SLR 014 PTCA DEB for treatment of de novo lesions in small coronary vessels, defined as reference vessel diameter (RVD) of 2.00 mm to 2.75 mm, in support of a pre-market approval (PMA) application to the United States (US) FDA. The Study will enroll up to 910 randomized subjects, up to 30 subjects in a parallel angiographic substudy, and up to 20 subjects in a parallel pharmacokinetic (pK) substudy, at up to 80 sites in the US, Canada, Brazil, Japan and Europe. A minimum of 50% of the subjects will be enrolled in the US.
Detailed description
Prospective, randomized controlled, single-blind, multicenter, clinical trial The study will enroll up to 910 randomized subjects, up to 30 subjects in a parallel angiographic substudy, and up to 20 subjects in a parallel pharmacokinetic (pK) substudy, at up to 80 sites in the US, Canada, Brazil, Japan and Europe. A minimum of 50% of the subjects will be enrolled in the US. Subjects who present with chronic coronary syndrome (CCS), unstable angina or stabilized non-ST elevation myocardial infarction (NSTEMI) with an indication for percutaneous coronary intervention (PCI) with planned intervention for de novo lesions in small coronary vessels (RVD 2.00 mm to 2.75 mm) and meeting all eligibility criteria will be randomized 1:1 to treatment of the identified target lesion with either the SELUTION SLR 014 PTCA DEB or contemporary DES. Randomized Cohort: * Intervention (DEB Strategy): Subjects randomized to the SELUTION SLR 014 PTCA DEB arm will receive lesion preparation according to the 3rd drug coated balloon (DCB) consensus (optimal balloon angioplasty with adjunct treatment using high-pressure balloon, intravascular lithotripsy, laser, rotational or orbital atherectomy, cutting or scoring balloon at the discretion of the operator as needed to reduce diameter stenosis to ≤ 30%). Subjects with lesions that are then best treated by provisional stenting (flow-limiting dissection, residual stenosis \> 30%) will receive a DES instead of the SELUTION DEB but remain in the SELUTION DEB group (intention to treat analysis). The DEB should not be used after DES implant. * Control (DES): Subjects randomized to the DES arm will receive treatment using any FDA approved "limus-based" DES, as per standard institutional practice. Angiographic Substudy: The angiographic substudy is a parallel registry consisting of up to 30 additional consecutive subjects meeting all eligibility criteria treated with the SELUTION DEB recruited at select study sites. These subjects will undergo angiography at 12 months post-procedure. Clinical follow-up will not extend beyond 12 months in this cohort. Pharmacokinetic (pK) Substudy: The pKsubstudy is a parallel registry consisting of up to 20 additional consecutive subjects meeting all eligibility criteria treated with the SELUTION DEB recruited at select study sites. This study will be conducted under an approved substudy protocol and will include blood draws at regular intervals to characterize the pK plasma profile of sirolimus. Primary Endpoint: Target lesion failure (TLF), defined as the composite of cardiac death, target-vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLR) at 12 months. MI includes spontaneous (Type 1) MI using the 4th Universal Definition of Myocardial Infarction (UDMI) and peri-procedural MI using the Society for Cardiac Angiography and Intervention (SCAI) definition.
Interventions
DEVICEPCI with SELUTION SLR DCB
After target lesion pre-dilatation and preparation , a SELUTION SLR 014 PTCA DEB study device should be selected with nominal diameter equal to the RVD of the target lesion (1:1 ratio) and length that allows approximately 2.00 mm longer than the proximal and distal edges of the target lesion (defined as the proximal and distal extent of predilation). If IVUS is performed to assess RVD, and DEB upsizing is deemed clinically necessary for optimal results, a maximum nominal DEB diameter of 3.0 mm is permitted. The SELUTION SLR 014 PTCA DEB should then be delivered, positioned in and deployed per instructions per use. The balloon should be inflated for 60 seconds provided that the patient can tolerate this duration. The minimum inflation time is 30 seconds.
DEVICEPCI with FDA approved "-limus" DES
For subjects randomized to the control group (DES), the treating physician will choose an FDA cleared DES and follow lesion preparation and stent deployment according to the Instructions per use (IFU) and institutional practices. The DES should be sized per IFU with respect to the vessel RVD. The use of IVUS or OCT is encouraged to guide optimal stent placement and assess final results. After DES deployment, additional balloon inflations should be performed as needed to obtain \< 30% residual diameter stenosis and resolve proximal or distal edge dissections greater than or equal to NHLBI grade B.
Sponsors
M.A. Med Alliance S.A.
NAMSA
Cordis US Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The randomized trial is a single-blind study. The physician performing the index procedure as well as study site personnel present at the index procedure will not be blinded, however every effort will be made to maintain blinding for the following: * Subjects and their families * Site personnel involved in conducting study assessments during follow-up Unblinding will only occur to protect subject rights, welfare, or well-being. The angiographic and pK substudy cohorts will not be blinded. The Clinical Events Committee (CEC) will be blinded to the treatment arm during the adjudication process.
Intervention model description
Single-Blind Randomized Control Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical Inclusion Criteria Subjects must meet all of the following clinical criteria to participate in the trial: 1. Subject is ≥ 18 years (or the minimum legal age as required by local regulations). 2. Female subjects of childbearing potential must have a negative pregnancy test ≤ 7 days before the procedure or are using a contraceptive device or drug. 3. Subject presents with chronic coronary syndromes \[CCS\] (manifest as documented angina or positive functional testing), unstable angina or stabilized non-ST elevation myocardial infarction (NSTEMI) (biomarkers stabilized or down trending) with an indication for PCI and planned intervention. 4. Subject can tolerate dual antiplatelet therapy with aspirin, plus either Clopidogrel, Prasugrel, or Ticagrelor. (Note: For subjects requiring oral anticoagulation, aspirin may be omitted based on investigator discretion). 5. Subject has life expectancy \> 1 year in the opinion of the investigator. 6. Subject is willing and able to provide informed consent and comply with study procedures and required follow-up evaluations. PK Sub- Study Inclusion Criteria: Subjects must meet all of the main protocol inclusion criteria to participate in the PK sub-study. Subjects must also meet the following additional PK sub-study inclusion criteria: 1\. Subject is willing and able to provide informed consent for the PK sub-study and comply with the PK sub-study procedures and required follow-up evaluations. Imaging Inclusion Criteria Subject's target lesion(s) must meet all of the following angiographic criteria for the subject to participate in the trial: 1. A single, target lesions that meet criteria can be treated in a single vessel. No non-target lesions can be treated within the target vessel in the index procedure. Non-target lesions within the target vessel can be staged for treatment \> 30 days from the index procedure. 2. Up to two (2) non-target lesions in up to two (2) non-target vessels may be treated, but successful PCI of the non-target lesions must be completed before randomization and treatment of the target lesion. 3. Target lesion is ≤ 36 mm in length. 4. Target lesion has diameter stenosis \> 50% and ≤ 99% with distal flow at least thrombolysis in myocardial infarction (TIMI) 2. 5. Target vessel has RVD of ≥ 2.00 mm and ≤ 2.75 mm \[by visual assessment\]. 6. Target lesion is within a native coronary artery or major branch. 7. A target lesion within a bifurcation is allowed only if a single vessel (either main vessel or side branch) is to be treated. 8. The identified target lesion has high probability for successful treatment with approved pre-treatment techniques and DEB alone based on Investigator assessment.
Exclusion criteria
* Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Target lesion failure (TLF) | 12 months | Target lesion failure (TLF) is defined as the composite of cardiac death, target-vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLR) at 12 months. MI includes spontaneous (Type 1) MI using the 4th Universal Definition of Myocardial Infarction (UDMI) and peri-procedural MI using the Society for Cardiac Angiography and Intervention (SCAI) definition. |
| PK Sub-study Primary Endpoint 1 | 6 months | PK parameters of C(max) |
| PK Sub-study Primary Endpoint 2 | 6 months | PK parameters of T(max) |
| PK Sub-study Primary Endpoint 3 | 6 months | PK parameters of AUC(last) |
| PK Sub-study Primary Endpoint 4 | 6 months | PK parameters of MRT(last) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Endpoint 1 | 12 months | Composite of all-cause mortality, target vessel MI or clinically driven target lesion revascularization |
| Secondary Endpoint 2 | Up to 7 days | Lesion success, defined as attainment of \< 30% residual stenosis of target lesion using any percutaneous method |
| Secondary Endpoint 3 | Up to 7 days | Procedure success, defined as attainment of \< 30% residual stenosis of the target lesion using the assigned study device only without the occurrence of in-hospital major adverse cardiac events (MACE), composite of all-cause death, MI or any clinically-driven TLR. |
| Secondary Endpoint 4 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Composite safety endpoint, defined as the patient-oriented composite of any death, any MI (spontaneous or peri-procedural), or any repeat revascularization. |
| Secondary Endpoint 5 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | All-Cause Mortality |
| Secondary Endpoint 6 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Cardiovascular Mortality |
| Secondary Endpoint 7 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | MI (spontaneous MI using the 4th UDMI, peri-procedural MI using SCAI and Academic Research Consortium \[ARC\]-2 definitions) |
| Secondary Endpoint 8 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Clinically-driven TLR |
| Secondary Endpoint 9 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | all TLR |
| Secondary Endpoint 10 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Clinically-driven Target Vessel Revascularization (TVR) |
| Secondary Endpoint 11 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | all TVR |
| Secondary Endpoint 12 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Non-target lesion revascularization |
| Secondary Endpoint 13 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | TLF |
| Secondary Endpoint 14 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Target vessel failure (TVF), defined as a composite of: cardiac death, target vessel MI (spontaneous or peri-procedural) and any clinically-driven TVR |
| Secondary Endpoint 15 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Stent or target lesion segment thrombosis (definite or probable) according to the ARC criteria for acute, subacute, late, very late and cumulative stent thrombosis |
| Secondary Endpoint 16 | 12 months | Bleeding Academic Research Consortium (BARC) class 2-5 |
| Secondary Endpoint 17 | Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years | Net adverse clinical events, defined as death, MI (spontaneous or peri-procedural), TVR, stent/target lesion segment thrombosis or bleeding (BARC types 2-5, assessed to 12 months) |
Countries
Germany, United States
Contacts
CONTACTRebecca Apruzzese
CONTACTSusanne Meis
PRINCIPAL_INVESTIGATORRon Waksman, MD
Medstar Health Research Institute
Outcome results
None listed