A Prospective Randomized Single-Blind Multicenter Study to Assess the Safety and Effectiveness of the SELUTION SLR™ 014 PTCA Drug Eluting Balloon in the Treatment of Subjects With De Novo Coronary Lesions in Small Vessels
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Coronary Artery Disease
- Sponsor
- M.A. Med Alliance S.A.
- Enrollment
- 960
- Locations
- 43
- Primary Endpoint
- PK Sub-study Primary Endpoint 4
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Clinical Inclusion Criteria
- •Subjects must meet all of the following clinical criteria to participate in the trial:
- •Subject is ≥ 18 years (or the minimum legal age as required by local regulations).
- •Female subjects of childbearing potential must have a negative pregnancy test ≤ 7 days before the procedure or are using a contraceptive device or drug.
- •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.
- •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).
- •Subject has life expectancy \> 1 year in the opinion of the investigator.
- •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:
Exclusion Criteria
- •Clinical Exclusion Criteria
- •Subjects who meet any of the following clinical criteria will be excluded from the trial:
- •Subject with known hypersensitivity or allergy to Sirolimus or its analogues.
- •Subject presents with NSTEMI and rising biomarkers, or ongoing chest pain or is hemodynamically instable.
- •Subject with history of ST-elevation myocardial infarction (STEMI) within 30 days of the index procedure.
- •Subject with planned major surgery within 30 days following the index procedure.
- •Subject with planned treatment of lesion involving aorto-ostial location.
- •Subject with PCI of a non-target vessel within ± 30 days of the index procedure.
- •Subject with history (within 6 months prior to index procedure) of New York Heart Association (NYHA) class III or IV heart failure.
- •Subject with history of active peptic ulcer or gastrointestinal bleeding within 6 months of the index procedure or other inability to comply with the recommended duration of dual antiplatelet therapy (DAPT).
Outcomes
Primary Outcomes
PK Sub-study Primary Endpoint 4
Time Frame: 6 months
PK parameters of MRT(last)
PK Sub-study Primary Endpoint 2
Time Frame: 6 months
PK parameters of T(max)
PK Sub-study Primary Endpoint 1
Time Frame: 6 months
PK parameters of C(max)
Target lesion failure (TLF)
Time Frame: 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 3
Time Frame: 6 months
PK parameters of AUC(last)
Secondary Outcomes
- Secondary Endpoint 1(12 months)
- Secondary Endpoint 10(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 6(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 12(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 3(Up to 7 days)
- Secondary Endpoint 4(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 5(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 2(Up to 7 days)
- Secondary Endpoint 7(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 13(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 9(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 8(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 16(12 months)
- Secondary Endpoint 17(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 11(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 14(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)
- Secondary Endpoint 15(Up to 7 days and at 1 month, 6 months, 12 months, 2 years, 3 years, 4 years, and 5 years)