← Product Code NXW · P230036
# Esprit BTK Everolimus Eluting Resorbable Scaffold System (P230036)
_ABBOTT MEDICAL · NXW · Apr 26, 2024 · Cardiovascular · APPR_
**Canonical URL:** https://fda.innolitics.com/device/P230036
## Device Facts
- **Applicant:** ABBOTT MEDICAL
- **Product Code:** NXW
- **Decision Date:** Apr 26, 2024
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Cardiovascular
- **Attributes:** Therapeutic
## Indications for Use
The Esprit™ BTK Everolimus Eluting Resorbable Scaffold System is indicated for improving luminal diameter in infrapopliteal lesions in patients with Chronic Limb Threatening Ischemia (CLTI) and total scaffolding length up to 170 mm with a reference vessel diameter of ≥ 2.5 mm and ≤ 4.00 mm.
## Device Story
Balloon-expandable resorbable scaffold system; delivers everolimus to infrapopliteal arteries to improve luminal diameter. Composed of PLLA backbone, PDLLA/everolimus coating, and platinum markers. Used in clinic/hospital settings by physicians for CLTI patients. Input: lesion anatomy; Output: mechanical scaffolding + drug elution (mTOR inhibition). Device resorbs over time. Clinical benefit: improved blood flow, wound healing, reduced amputation risk. Output used by physicians to restore patency; affects decision-making by providing alternative to permanent metallic stents.
## Clinical Evidence
Prospective, multicenter, single-blinded RCT (LIFE-BTK) with 261 subjects (173 Esprit BTK, 88 PTA). Primary safety (6-mo MALE + 30-day POD): 96.9% (Esprit) vs 100% (PTA), p=0.0019 (non-inferior). Primary effectiveness (1-yr limb salvage/patency): 74.5% (Esprit) vs 43.7% (PTA), p<0.0001 (superior). PK sub-study (n=9) confirmed systemic exposure limits.
## Technological Characteristics
Resorbable scaffold (100% PLLA backbone) with PDLLA/everolimus coating (100 μg/cm²). 5F rapid-exchange delivery system. Platinum markers for radiopacity. Sterilized via e-beam radiation. Finite element analysis (FEA) used for fatigue/crush resistance. MRI compatible (up to 7.0 Tesla).
## Regulatory Identification
The absorbable scaffold is for improving luminal diameter for the treatment of lesions in native infrapopliteal arteries.
## Reference Devices
- XIENCE V™ Drug Eluting Stent System ([P070015](/device/P070015.md))
- Absorb GT1™ Bioresorbable Vascular Scaffold ([P150023](/device/P150023.md))
- XIENCE Alpine™ Stent System ([P110019](/device/P110019.md)/S070)
## Submission Summary (Full Text)
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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
## I. GENERAL INFORMATION
Device Generic Name: Stent, infrapopliteal, absorbable
Device Trade Name: Esprit™ BTK Everolimus Eluting Resorbable Scaffold System
Device Procode: NXW
Applicant’s Name and Address: Abbott Medical
3200 Lakeside Drive
Santa Clara, CA 95054
Date of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P230036
Date of FDA Notice of Approval: April 26, 2024
Breakthrough Device: Granted breakthrough device status on July 17, 2017, for improving luminal diameter in infrapopliteal lesions in patients with critical limb ischemia (CLI).
## II. INDICATIONS FOR USE
The Esprit™ BTK Everolimus Eluting Resorbable Scaffold System is indicated for improving luminal diameter in infrapopliteal lesions in patients with Chronic Limb Threatening Ischemia (CLTI) and total scaffolding length up to 170 mm with a reference vessel diameter of ≥ 2.5 mm and ≤ 4.00 mm.
## III. CONTRAINDICATIONS
The Esprit™ BTK Everolimus Eluting Resorbable Scaffold System is contraindicated for use in:
- Patients who cannot tolerate, including allergy or hypersensitivity to, procedural anticoagulation or the post-procedural antiplatelet regimen.
- Patients with hypersensitivity or contraindication to everolimus or structurally related compounds, or known hypersensitivity to scaffold components (poly(L-lactide), poly(D, L-lactide), platinum).
## IV. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the Esprit™ BTK Everolimus Eluting Resorbable Scaffold System labeling.
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# V. DEVICE DESCRIPTION
The Esprit™ BTK Everolimus Eluting Resorbable Scaffold System (Esprit BTK System) is composed of a balloon expandable scaffold and a delivery system. The Esprit BTK Scaffold is a resorbable polymeric scaffold with a drug and resorbable polymeric coating. The Esprit BTK Scaffold is temporary and will resorb over time. A schematic of the system is provided in Figure 1. The Esprit BTK System is available in the size matrix noted in Table 1.
Figure 1: Schematic of the Esprit BTK System (not to scale)
Table 1. Esprit BTK System Size Matrix
| Labeled Diameter (mm) | Lengths (mm) | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | 9 | 12 | 15 | 18 | 23 | 28 | 33 | 38 |
| 2.5 | X | X | X | X | X | X | X | X |
| 2.75 | X | X | X | X | X | X | X | X |
| 3 | X | X | X | X | X | X | X | X |
| 3.5 | X | X | X | X | X | X | X | X |
| 3.75 | X | X | X | X | X | X | X | X |
# Esprit BTK Scaffold
The Esprit BTK Scaffold consists of a resorbable scaffold backbone comprised of $100\%$ poly (L-lactide) (PLLA) and a coating comprised of the active pharmaceutical ingredient everolimus and resorbable poly (D, L-lactide) (PDLLA). Four platinum markers, two each at the proximal and distal ends of the scaffold, are included for radiopacity.
# Esprit BTK delivery system
The rapid-exchange (RX) balloon expandable delivery system is a 5F $(0.070^{\prime \prime} / 1.8\mathrm{mm})$ catheter with a semi-compliant balloon with two radiopaque markers located on the catheter shaft to indicate scaffold positioning. The catheter is designed to have a working length of $145~\mathrm{cm}$ , a single access port to the inflation lumen, and compatibility with guidewires $\leq 0.014''$ .
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# Drug Component - Everolimus
The Esprit BTK Scaffold is coated with a drug / polymer matrix that consists of $50\mathrm{wt}\%$ of the active pharmaceutical ingredient, everolimus, and $50\mathrm{wt}\%$ PDLLA. Everolimus has been evaluated through a number of different clinical studies and is known to have a wide therapeutic window. The drug (everolimus) dose density for Esprit BTK Scaffold is 100 $\mu \mathrm{g} / \mathrm{cm}^2$ .
Everolimus (Chemical name: 40-O-(2-hydroxyethyl)-rapamycin) (Figure 2) is a semisynthetic macrolide immunosuppressant obtained through chemical modification of rapamycin. Rapamycin (INN: Sirolimus) is a secondary macrolide metabolite that is produced by certain actinomycete strains.
Figure 2: Chemical Structure of Everolimus
At the cellular level, everolimus inhibits growth factor-stimulated cell proliferation. At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12 (FK 506 Binding Protein). This complex binds to and interferes with FRAP (FKBP- 12 Rapamycin Associated Protein), also known as mTOR (mammalian Target of Rapamycin), leading to inhibition of cell metabolism, growth, and proliferation by arresting the cell cycle at the late G1 stage.
# VI. ALTERNATIVE PRACTICES AND PROCEDURES
There are several other alternatives for the correction of chronic limb threatening ischemia, including medications to help relieve symptoms and improve blood flow to the legs and lifestyle changes such as increasing physical activity, smoking cessation, diet modification and weight loss programs. Percutaneous interventions (balloon angioplasty, atherectomy) and bypass surgery can also be used to restore patency to below the knee
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arteries and improve blood flow. A combination of any of the above methods may be used for optimal treatment. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.
## VII. MARKETING HISTORY
The Esprit™ BTK Everolimus Eluting Resorbable Scaffold System has not been marketed in the United States or any foreign country.
## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
Below is a list of potential adverse effects associated with the use of the device. These adverse effects include, but are not limited to:
- Allergic reaction or hypersensitivity to: contrast agent, anesthesia, scaffold materials (poly [L-lactide] [PLLA], poly [D, L-lactide] [PDLLA], platinum, or everolimus), and drug reactions to anticoagulation, or antiplatelet drugs
- Vascular access complications which may require transfusion or vessel repair, including:
- Catheter site reactions
- Bleeding (ecchymosis, oozing, hematoma, hemorrhage, retroperitoneal hemorrhage)
- Arteriovenous fistula, pseudoaneurysm, aneurysm, dissection, perforation / rupture, and laceration
- Embolism (air, tissue, plaque, thrombotic material, or device)
- Peripheral ischemia
- Target artery complications which may require additional intervention, including:
- Total occlusion or abrupt closure
- Arteriovenous fistula, pseudoaneurysm, aneurysm, dissection, perforation / rupture
- Embolism (air, tissue, plaque, thrombotic material, or device)
- Artery or scaffold thrombosis
- Stenosis or restenosis
- Vasospasm
- Tissue prolapse / plaque shift
- Bleeding (non-access site)
- Additional surgery such as peripheral artery bypass graft surgery or amputation
- Peripheral nerve injury, neuropathy
- Compartment syndrome
- Tissue necrosis, gangrene, ulcer and acute limb ischemia
- Reperfusion injury
- New or worsening pain
- Intervention due to
- Damaged scaffolds
- Partial scaffold deployment
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○ Scaffold migration/Unintentional placement of scaffold
- Other general surgical risks, including:
- Cardiac arrhythmias (including conduction disorders, atrial and ventricular arrhythmias, and blocks)
- Stroke / cerebrovascular accident (CVA) and transient ischemic attack (TIA)
- Venous thromboembolism (including pulmonary embolism)
- Nausea and vomiting
- Hypotension / hypertension
- Infection – local and systemic (including post-procedural)
- Fever
- Blood cell disorders including heparin induced thrombocytopenia (HIT) and other coagulopathy
- Death
- System organ failures:
- Cardiac Failure
- Cardio-respiratory arrest (including pulmonary edema)
- Respiratory failure
- Renal failure
- Shock
Adverse events associated with daily oral administration of everolimus in doses varying from 1.5 mg to 10 mg daily can be found in the labels for the drug. The risks described below include the anticipated adverse events relevant for the cardiac population referenced in the contraindications, warnings, and precaution sections of the everolimus labels and / or observed at incidences ≥ 10% in clinical trials with oral everolimus for different indications. Refer to the drug labels for more detailed information and less frequent adverse events.
- Abdominal pain
- Anemia
- Angioedema (increased risk with concomitant angiotensin converting enzyme [ACE] inhibitor use)
- Arterial thrombotic events
- Bleeding and coagulopathy (including hemolytic uremic syndrome [HUS], thrombotic thrombocytopenic purpura [TTP], and thrombotic microangiopathy; increased risk with concomitant cyclosporine use)
- Constipation
- Cough
- Diabetes mellitus
- Diarrhea
- Dyspnea
- Embryo-fetal toxicity
- Erythema
- Erythroderma
- Headache
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- Hepatic artery thrombosis (HAT)
- Hepatic disorders (including hepatitis and jaundice)
- Hypersensitivity to everolimus active substance, to other rapamycin derivatives
- Hypertension
- Infections (bacterial, viral, fungal, or protozoan infections, including infections with opportunistic pathogens). Polyoma virus-associated nephropathy (PVAN), JC virus-associated progressive multiple leukoencephalopathy (PML), fatal infections and sepsis have been reported in patients treated with oral everolimus.
- Kidney arterial and venous thrombosis
- Laboratory test alterations (elevations of serum creatinine, proteinuria, hypokalemia, hyperkalemia; hyperglycemia, dyslipidemia including hypercholesterolemia and hypertriglyceridemia; abnormal liver function tests; decreases in hemoglobin, lymphocytes, neutrophils, and platelets)
- Lymphoma and skin cancer
- Male infertility
- Menstrual irregularities
- Nausea
- Nephrotoxicity (in combination with cyclosporine)
- Non-infectious pneumonitis (including interstitial lung disease)
- Oral ulcerations
- Pain
- Pancreatitis
- Pericardial effusion
- Peripheral edema
- Pleural effusion
- Pneumonia
- Pyrexia
- Rash
- Renal failure
- Upper respiratory tract infection
- Urinary tract infection
- Venous thromboembolism
- Vomiting
- Wound healing complications (including wound infections and lymphocele)
For the specific adverse events that occurred in the clinical study, please see Section X below.
## IX. SUMMARY OF NONCLINICAL STUDIES
### A. Biocompatibility Studies
The Esprit BTK System (the scaffold and the delivery system) has gone through a thorough biocompatibility evaluation per the ISO 10993-1 (2018): Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing within a Risk Management Process and the FDA Guidance (2023): Use of International Standard ISO 10993-1, “Biological
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Evaluation of Medical Devices Part 1: Evaluation and Testing with a Risk Management Process." All testing was performed in compliance with the ISO 10993 series wherever applicable and in accordance with FDA Title 21, CFR Part 58: Good Laboratory Practice for Non-Clinical Laboratory Studies.
The Esprit BTK Scaffold is classified as a long-term implant contacting circulating blood for $>30$ days. The Esprit BTK Scaffolds (uncoated and drug-coated) were tested separately from the Esprit BTK delivery system. The Esprit BTK delivery system is classified as an externally communicating device contacting circulating blood for $\leq 24$ hours.
All testing performed met the pre-specified acceptance criteria. The test results of Esprit BTK Scaffold and Esprit BTK delivery system are summarized in Table 2.
Table 2. Biocompatibility Tests of the Esprit™ BTK Scaffold and Delivery System
| Endpoint | Test | Scaffold | Delivery System | Results |
| --- | --- | --- | --- | --- |
| Cytotoxicity (ISO 10993-5) | MEM Elution Assay using L-929 Fibroblasts Cells | X | X | Pass Non-cytotoxic |
| Sensitization (ISO 10993-10) | Guinea Pig Maximization Test | X | X | Pass Non-sensitizer |
| Irritation (ISO 10993-23) | Intracutaneous Reactivity Test | X | X | Pass Non-irritant |
| Material-mediated Pyrogenicity (ISO 10993-11) | Material Mediated Rabbit Pyrogenicity Test | X | X | Non-pyrogenic |
| Acute Systemic Toxicity (ISO 10993-11) | Acute Systemic Injection Test | X | X | Pass Non-toxic |
| Hemocompatibility (ISO 10993-4) | Hemolysis (Direct and Indirect) Test | X | X | Pass Non-hemolytic |
| | Complement Activation (SC5b-9) Test | X | X | Pass Non-compliment activator |
| | In vivo Thrombogenicity Test | X | X | Pass Non-thrombogenic |
| | Partial Thromboplastin Time (PTT) Test | | X | Comparable to comparator |
| | Platelet and Leukocyte Count Assay (P&L) | | X | Pass Non-thrombogenic |
| Genotoxicity (ISO 10993-3) | Bacterial Reverse Mutation Assay (Ames Test) | X | | Pass Non-mutagenic |
| | In Vitro Chromosomal Aberration | X | | Pass Non-mutagenic |
| | Clastogenicity in Mammalian Cells (Forward Mutation) | X | | Pass Non-Clastogenic |
| | Mammalian Erythrocyte Micronucleus Test | X | | Pass Non-mutagenic |
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Scaffold implantation and delivery system thrombogenicity were evaluated as part of the in vivo safety and pharmacokinetics (PK) animal studies which concluded no adverse local tissue reactions following implantation of Esprit BTK Scaffold nor thrombogenicity risks of the Esprit BTK System. The Esprit BTK Scaffold leveraged XIENCE V™ Drug Eluting Stent System (PMA approved under P070015) carcinogenicity and reproductive toxicity studies for the clinical drug doses used for the disease indication. Extensive material assessment (theoretical compositional profiling based on the chemical characterization data from Absorb GT1™ Scaffold) and toxicological risk assessment in addition to genotoxicity testing were performed on the Esprit BTK Scaffold to assess subchronic/chronic systemic toxicity, genotoxicity, and carcinogenicity of the scaffold. The assessment concluded no risks of these biological endpoints.
# B. In Vitro Engineering Testing
In vitro engineering testing, in accordance with "Guidance for and FDA Staff- Non-Clinical Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems", April 2010; ISO 25539-2:2012 Cardiovascular Implants - Endovascular devices - Part 2: Vascular Stents; ISO 10555-1: 2013/Amd 1:2017 Intravascular Catheters - Sterile and Single-use Catheters - Part 1: General Requirements - Amendment; ISO 10555-4:2013 Intravascular Catheters - Sterile and Single-use Catheters - Part 4: Balloon Dilatation Catheters, was conducted on the Esprit BTK System. The testing is summarized in Table 3.
Table 3. Esprit™ BTK System In Vitro Engineering Testing
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Scaffold Dimensional and Functional Testing | | | |
| Dimensional Verification | Measure the scaffold dimensions for: • Nominal Scaffold Inner Diameter (ID) • Scaffold Ring Strut Width and Scaffold Tube Wall Thickness • Maximum Crossing Profile Diameter • Maximum Balloon Outside the Stent | Scaffold dimensions shall meet specified/labeled dimensions. | Pass |
| Length Change (Nominal and Post-Dilated) | Percentage change in length of the scaffold between the un-deployed mounted (crimped) condition and the expanded conditions (nominal and post-dilated diameters at three rotational orientations) after balloon deflation. | The change in scaffold length from un-deployed length to expanded length after balloon deflation shall be ≤ 10%. | Pass |
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PMA P230036: FDA Summary of Safety and Effectiveness Data
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Recoil (Nominal and Post-Dilated) | Percentage by which the outer diameter of a balloon-expandable scaffold decreases from its expanded diameter while on the inflated delivery balloon to its relaxed diameter after deflating the balloon at three rotational orientations. | The percentage of recoil shall be ≤ 10%. | Pass |
| Radial Strength (Nominal and Post-Dilated) | Determines the radial force or pressure required to permanently deform a deployed scaffold at nominal and post-dilated deployment diameters. | The radial force or pressure required to permanently deform the deployed scaffold shall be ≥ 350 mmHg. | Pass |
| Uniformity of Expansion | Determine the difference between the largest and smallest diameter measurement on a single scaffold deployed unconstrained to its labeled diameter after deflation of the balloon at three rotational orientations. | The difference between the largest and smallest diameter measurement on a single scaffold deployed unconstrained to its labeled diameter after deflation of the balloon must meet pre-specified values: 2.5 mm: ≤ 0.3 mm 2.75 mm: ≤ 0.3 mm 3.0 mm: ≤ 0.4 mm 3.5 mm: ≤ 0.5 mm 3.75 mm: ≤ 0.5 mm | Pass |
| Ring Tension | Determine the limit of expansion before strut fracture. | The limit of expansion before strut fracture shall be at least 0.5 mm greater than the labeled diameter. | Pass |
| Scaffold Dislodgement (Distal and Proximal) | Determine the force required to dislodge a balloon-expandable scaffold from its original, crimped position on a delivery system in either the distal or proximal direction. | The force required to dislodge the scaffold from its crimped position on the delivery system shall be greater than pre-specified values, depending on scaffold diameter and length. | Pass |
| Scaffold Markers (Nominal and Post-Dilated) | Verify the presence of the scaffold markers after subjecting the scaffold to an environment similar to that seen in ordinary use, including post-dilatation. | There shall be no marker loss upon deployment. | Pass |
| Scaffold Placement and Visual Inspection | Verify there is no catheter damage and appropriate scaffold placement between the balloon markers in the crimped state. | The catheter must be free from kinks and damage. Scaffold must be appropriately placed between the balloon markers. | Pass |
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PMA P230036: FDA Summary of Safety and Effectiveness Data
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Guiding Catheter Pullback | Test the ability of an un-deployed scaffold system to be withdrawn into a guiding catheter. | The system will sustain 1 cycle of pullback through a 6F / 0.070”/ 1.8 mm inner diameter guiding catheter without scaffold movement. | Pass |
| Radiopacity | Evaluate the ability to visualize the scaffold using fluoroscopy during scaffold delivery, deployment, and after implantation. | The scaffold shall be able to be visualized using angiographic imaging during scaffold delivery, deployment and after implantation to assure proper scaffold placement. | Pass |
| Scaffold Integrity | Evaluate scaffolds for damage which could contribute to clinical complications after deployment to the post-dilated diameter. | The scaffold must meet the following to demonstrate scaffold integrity:
• Scaffold Markers requirement
• Coating Integrity requirement
• Ring Tension requirement
• Structural Radial Fatigue requirement | Pass |
| Stress/Strain Analysis/Fatigue Analysis (Finite Element Analysis) | Evaluate the durability and integrity of the scaffold using Finite Element Analysis (FEA). The FEA analysis simulated pulsatile and crush loading conditions relevant to the BTK anatomy. | The FEA analysis must demonstrate that the scaffold maintains acceptable fatigue safety using the Goodman fatigue analysis with a safety factor > 1. | Pass |
| Accelerated Durability Testing (Structural Radial, Embolic Radial and Crush Fatigue) | Characterize the structural and embolic durability of scaffolds with up to 1-year pulsatile and crush fatigue cycling. | Structural Durability: Scaffold must maintain structural integrity at 3 months.
Embolic Radial Fatigue: Tested for characterization of particulates. | Pass/Acceptable Outcomes |
| Scaffold Percent Surface Area | Percentage which indicates the amount of contact between the scaffold and the scaffolded vessel wall at a labeled scaffold diameter and length. | Scaffold Percent Surface Area is calculated for characterization. | Acceptable Outcomes |
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PMA P230036: FDA Summary of Safety and Effectiveness Data
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Magnetic Resonance Imaging (MRI) Safety and Compatibility | Provide confirmation that the scaffold poses no known hazards resulting from exposure to MR environment in magnetic fields up to static field 7.0 Tesla. | The scaffold must meet the requirements of FDA Guidance documents, Testing and Labeling Medical Devices for Safety in the Magnetic Resonance (MR) Environment (dated December 11, 2014), ASTM F2182-11a, ASTM F2052-14, Magnetically Induced Torque Test using Qualitative Torque, ASTM F2119-07 (reapproved 2013). The conditions under which the device can be safely scanned are reflected in the Instructions for Use (IFU). | Acceptable Outcomes |
| Scaffold Mechanical Properties | Characterize the mechanical properties (i.e., tensile strength in axial and circumferential directions) of PLLA expanded tubing. | The scaffold mechanical properties are evaluated for characterization. | Acceptable Outcomes |
| Dogboning | Visually determine if the balloon shoulders are growing larger than the scaffold outer diameter at the Rated Burst Pressure of the scaffold delivery system. | The unconstrained balloon diameter is evaluated relative to the scaffold outer diameter for characterization. | Acceptable Outcomes |
| Scaffold Flare | Determine the change in distance between the OD of the scaffold and the OD of the balloon as manufactured and after tracking through a tortuous path, at the distal and proximal ends. | The change in distance between the OD of the scaffold and the OD of the balloon is evaluated for characterization. | Acceptable Outcomes |
| Radial Stiffness (Nominal and Post-Dilated) | Determine the radial stiffness at nominal and post-dilated deployment diameters. | Radial Stiffness is evaluated for characterization. | Acceptable Outcomes |
| Vessel Straightening and Wall Conformity | Vessel Straightening: Measure the amount of vessel straightening that occurs when a stent or scaffold is deployed in a curved vessel. Wall Conformity: Visual assessment of scaffold apposition. | Vessel straightening, determined by quantitative comparison of native vessel vs post-deployment radius of curvature, is evaluated for characterization. Assessment of wall conformity/apposition is evaluated for characterization. | Acceptable Outcomes |
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| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Kink Resistance | Characterize the change in lumen diameter as the scaffold is bent. | Determine the smallest radius of curvature that the scaffold can withstand without kinking or diameter reduction of >50% for characterization. | Acceptable Outcomes |
| Crush Resistance | Characterize the ability of the scaffold to recover its deployment diameter when subjected to worst-case parallel plate crush deformation. | The ability of the scaffold to recover its deployment diameter from worst-case parallel plate crush deformation is evaluated for characterization. | Acceptable Outcomes |
| Delivery System Dimensional and Functional Testing | | | |
| Dimensional Specification | Measure the catheter dimensions of the delivery system • Balloon Shoulder to Marker (Distal and Proximal) • Tip Length • Tip Entry Outer Diameter • Outer Member Outer Diameter • Hypotube Outer Diameter • Notch Outer Diameter • Proximal Shaft Marker Locations (Femoral and Brachial) • Total Catheter Length • Distal Catheter Length • Guidewire Lumen Dimensions | Catheter dimensions shall meet specified/labeled dimensions. | Pass |
| Catheter Preparation | Determine the number of double negative aspiration procedures necessary to displace air from the balloon with contrast medium. | The number of double negative aspiration procedures necessary to displace air from the balloon with contrast medium shall be no greater than 3. | Pass |
| Balloon Deflation Time | Measure the deflation time of the scaffold delivery system. | Deflation time shall be ≤30 seconds. | Pass |
| Balloon Rated Burst Pressure | Determine the pressure at which the balloon ruptures. | The pressure at which the balloon ruptures shall be ≥235 psi (16 atm / 1621 kPa). | Pass |
| Maximum Compliance Label Pressure | Determine the pressure at which the balloon ruptures. | Maximum compliance label pressure shall be ≥264 psi (18 atm / 1824 kPa). | Pass |
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PMA P230036: FDA Summary of Safety and Effectiveness Data
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Tensile Strength | Determine the tensile strength of:
• Catheter Seal Tensile (Proximal Seal)
• Catheter Seal Tensile (Guidewire Notch and Outer member to Hypotube only)
• Proximal Adaption Tensile
• Tip Tensile | ≥ 2.2 N (0.5 lbf) – 15.5 N (3.5 lbf), depending on system diameter and bond. | Pass |
| Inner Member Lumen Collapse | Determine if Inner Member (IM) collapse is reversible (guide wire movement possible) at negative pressure after inflation to specified pressures. | When the inflation pressure is ≤ 300 psi 20 ATM / 2068 kPa), the IM must recover after inflation. | Pass |
| Balloon Fatigue Resistance | Determine if a balloon can withstand repeat inflations to rated burst pressure. | The system shall withstand 10 repeated inflations at the rated burst pressure. | Pass |
| Corrosion Resistance | Determine whether the hypotube of the proximal shaft subassembly is corrosion resistant. | Corrosion shall not be present at 10x magnification. | Pass |
| **Delivery system Characterization Testing** | | | |
| Catheter Torque | Determine the number of rotations required to break the joints and/or materials or to lose functional integrity. | The number of rotations required to break the joints and/or materials or to lose functional integrity shall be > 1. | Pass |
| Kink/Flex | Determine the minimum radius of curvature at which the catheter kinks. | The minimum radius of curvature at which the catheter kinks shall be below a pre-specified value. | Pass |
| Balloon Inflation Time | Measure the inflation time of the scaffold delivery system. | Inflation time is evaluated for characterization. | Pass |
| Compliance | Provide the scaffold inner diameter (ID) data which equates to the balloon outer diameter over the full range of recommended inflation pressures. | Characterize for development of the balloon compliance curve. | Pass |
| **Esprit BTK System Design Validation Testing** | | | |
| Delivery, Deployment and Retraction (DDR) | Demonstrate that the Esprit BTK System is able to permit safe, consistent and accurate access to an intended location, deployment of the scaffold, and withdrawal of the delivery system. | The scaffold delivery system shall demonstrate the ability to permit safe, consistent and accurate access to the intended location, accurate deployment of the stent and withdrawal of the delivery system. | Pass |
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PMA P230036: FDA Summary of Safety and Effectiveness Data
| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Aseptic Presentation | Demonstrate that the Esprit BTK System is able to be unpackaged and presented aseptically according to the instructions for use. | There is no visible damage / breach in sterile barrier system integrity. The user is able to identify where to begin opening the package. The sterile contents can be aseptically presented. | Pass |
| Catheter Radiopacity | Demonstrate that the Esprit BTK delivery system catheter is visible during access, placement, deployment, and withdrawal using fluoroscopy. | The radio-detectability of the delivery catheter is clinically acceptable. The user is able to visualize the delivery system balloon markers during the advancement, placement, deployment, post-deployment and retraction into the guiding sheath / introducer sheath. | Pass |
| Safe Disposal | Demonstrate that the Esprit BTK System can be disposed of safely according to the instructions for use. | User can dispose of the evaluation device in a safe manner in accordance with the IFU. | Pass |
| Coating Testing | | | |
| Coating Integrity | Determine the percent compromised surface area of the scaffold coating after expanding the scaffold to the largest post-dilated diameter within the design. | The percent compromised surface area of the scaffold coating shall not be greater than pre-specified value. | Pass |
| Tracking Particulate | Count and size particulates generated by tracking one test unit through a tortuosity and then deploying in a 15 mm radius bend. | Particulates with length ≥ 10 μm shall be less than or equal to 6000. Particulates with length ≥ 25 μm shall be less than or equal to ≤ 600. | Pass |
| Dry Adhesion | Determine the adhesion of the hydrophilic coating on a scaffold delivery system shaft. | The hydrophilic coating remains largely intact on the scaffold delivery system shaft. | Pass |
| Coefficient of Friction | Determine the kinetic coefficient of friction of hydrophilically-coated shafts on scaffold delivery systems. | The Coefficient of Friction shall be below pre-specified values. | Pass |
| Coating Thickness | Measure the coating thickness along the length of the drug coated scaffold. | The coating thickness along the length of the scaffold is evaluated for characterization. | Acceptable Outcomes |
| Longitudinal Content Uniformity | Evaluate the intra-scaffold drug content uniformity along the length of the scaffold. | The content uniformity along the length of the scaffold is evaluated for characterization. | Acceptable Outcomes |
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| Test | Test Description | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Circumferential Content Uniformity | Evaluate the intra-scaffold drug content uniformity around the circumference of the scaffold. | The content uniformity along the circumference of the scaffold is evaluated for characterization. | Acceptable Outcomes |
| Coating Morphology | Analyze the coating surface and coating microstructure at multiple locations on each scaffold. | The coating surface and coating microstructure are evaluated for characterization. | Acceptable Outcomes |
| Coating Adhesion After Balloon Rupture | Characterize the coating integrity of the scaffold at the nominal balloon expansion and after over expansion until the balloon ruptures. | Coating adhesion after balloon rupture is evaluated for characterization. | Acceptable Outcomes |
| Hydrophilic Coating Integrity Visual Inspection | Perform a visual assessment of the catheter coating integrity on the surface of the catheters before and after simulated use. | A visual assessment of the catheter coating integrity is performed for characterization. | Acceptable Outcomes |
# C. Chemistry, Manufacturing & Controls (CMC) Testing
Where applicable, International Conference on Harmonization (ICH) Guidelines were followed for the testing routinely performed on the Esprit BTK System as part of the finished product release. This testing is summarized in Table 4.
Table 4. Esprit BTK System Analytical Release Testing
| Test | Test Description |
| --- | --- |
| Appearance | A visual inspection is conducted to verify that the Esprit BTK System meets appearance specifications for finished product release. |
| Identity | Tests are conducted to verify the identity of the drug substance, everolimus, on the Esprit BTK System using two different methods, Ultraviolet/Visible Spectroscopy and High Performance Liquid Chromatography. |
| Total Content | Assay is conducted to quantitatively verify that the total amount of the drug substance, everolimus, on the Esprit BTK System meets specifications for finished product release. |
| Content Uniformity | Multiple scaffolds are tested to verify that the uniformity of the drug content between individual Esprit BTK Scaffold is within specifications established for finished product release. |
| Degradation Products /Impurities | The amount and type of everolimus degradation products / impurities are quantitatively verified to meet specifications established for finished product release |
| Tracking Particulate | The test collects particles generated acutely from the delivery, deployment, and withdrawal of either a single scaffold or two scaffolds deployed in an overlapped configuration. |
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| Test | Test Description |
| --- | --- |
| Bacterial Endotoxin USP <85> | The amount of bacterial endotoxins is verified to be within specification limits established for finished product release. |
| Drug Release | The drug release profile of the drug substance, everolimus, is verified to meet specifications established for finished product release. |
| Number Average Molecular Weight | The number average molecular weight (M_{n}) is verified to be within specification limits established for finished product release. |
| Sterility | The Esprit BTK product is released by verifying that the dose complied with validated sterilization parameters and satisfies the requirement for labeling the finished goods as sterile. |
| Residual Solvent | The amount of residual solvent (acetone) is verified to meet specification limits established for finished product release. |
| BHT Content | The BHT content on the Esprit BTK System is quantitatively verified to meet specification limit established for finished product release. |
## D. Stability/Shelf Life
Stability studies were conducted to establish a shelf life / expiration date for the Esprit BTK System. The stability test attributes, including Appearance, Total Content, Impurities and Degradation Products, Drug Release, Number Average Molecular Weight, Whole Packaging Integrity, Particulate Matter, and Bacterial Endotoxin, were performed at each of the preselected stability time points. BHT Content is tested for characterization only. Analytical test attributes, including Content Uniformity, Identity and Residual Solvent, are performed for initial lot release. Functional testing, including Scaffold Dislodgement, Scaffold Ring Tension, and Radial Strength, was performed at the initial time point. Testing to establish container closure integrity was conducted to ensure that sterility was maintained during the shelf life of the product. The data generated to-date support a shelf life of 12 months for the Esprit BTK System.
## E. Sterilization
The Esprit BTK System is sterilized by means of electron-beam (e-beam) radiation, in-house at the Abbott Vascular, Temecula manufacturing facility, to meet a Sterility Assurance Level (SAL) of $10^{-6}$ in accordance with ISO 11137-1:2006/Amd1:2013 /Amd2:2018, Sterilization of health care products – Radiation – Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices. Pursuant to the validation requirements, the Esprit BTK System has been successfully qualified for one time e-beam sterilization. In addition, the amount of bacterial endotoxins was verified to be within the specification limits.
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F. Packaging
The Esprit BTK System is packaged in a configuration that ensures sterility and provides protection during handling, storage, and delivery of the final product throughout the labeled shelf life. The packaging validation is composed of the following three components:
- Packaging process validation, which includes a visual inspection of all seals, whole package integrity, seal integrity, and seal strength testing at the nominal, upper and lower parameters of the sealing process.
- Packaging system performance testing, which includes a visual inspection of all seals, whole package integrity, seal integrity, and seal strength testing at the upper and lower limits of the package sealing process parameters following package sterilization, extreme conditioning, and transportation simulation conditioning.
- Packaging system stability testing, which tests the package material for degradation over time, including potential sterilization effects, throughout the product shelf-life.
G. In Vivo Animal Studies
A series of GLP in vivo studies were conducted in the porcine coronary artery model in order (a) to evaluate the in vivo pharmacokinetic profile, and (b) to demonstrate the in vivo safety. Studies were conducted using the Absorb GT1™ Bioresorbable Vascular Scaffold (BVS) (PMA approved under P150023) or Esprit BTK Scaffold, as described below. The Esprit BTK Scaffold and the Absorb GT1™ BVS are composed of identical polymer materials (PLLA, PDLLA) and share identical chemical and manufacturing controls which regulate scaffold degradation. Based on the similarities in materials and design between the Esprit BTK System and the Absorb GT1 BVS System, the assessments conducted for the Absorb GT1 BVS were leveraged to support the Esprit BTK Scaffold.
This in vivo testing was conducted in accordance with one or more of the following general regulations and guidance documents and the consensus documents:
- Good Laboratory Practices Regulations (21 CFR § 58)
- Guidance for Industry and FDA Staff: General Considerations for Animal Studies for Cardiovascular Devices CDRH. 2010
- Guidance for Industry and FDA Staff: Non-Clinical Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, 2010
- Schwartz, R. S., et al. "Drug-Eluting Stents in Preclinical Studies: Updated Consensus Recommendations for Preclinical Evaluation." Circ Cardiovasc Intervent 1(2): 143-153, 2008.
- Schwartz, R. S., et al. "Drug-eluting stents in preclinical studies: recommended evaluation from a consensus group." Circulation 106(14): 1867-1873, 2002.
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- Schwartz, R. S., et al. "Preclinical evaluation of drug-eluting stents for peripheral applications: recommendations from an expert consensus group." Circulation 110(16): 2498-2505, 2004.
A summary of the preclinical in vivo studies conducted is provided below and in Table 5.
# 1. In Vivo Pharmacokinetics
A 90-day PK study was conducted to characterize the in vivo pharmacokinetics of the Esprit BTK Scaffold, including the drug release profile and drug concentrations in arterial tissues, distal vital organs and systemic circulation. The Esprit BTK Scaffold maintains drug concentrations in implanted arterial tissues up to 90 days. As the drug release profiles between the Esprit BTK Scaffold and the Absorb GT1™ BVS are bioequivalent, the results of the 300-day PK study conducted for Absorb GT1 BVS are leveraged for the Esprit BTK Scaffold to characterize the drug elution profile at longer time points ( $\geq$ 120 days) when $>95\%$ to $100\%$ of drug is released.
# 2. In Vivo Degradation
Three in vivo degradation studies were conducted for the Absorb GT1 BVS in order to determine the in vivo degradation profile. These studies are inclusive of time points from 28 days to 42 months, with results demonstrating complete scaffold resorption by approximately 36 months.
# 3. In Vivo Safety
Three in vivo safety studies were conducted in the porcine coronary artery model to demonstrate in vivo safety of the Esprit BTK Scaffold relative to XIENCE Alpine™ Stent System (P110019 / S070) (28 days) and Absorb GT1 BVS (90, 180 days). In these studies, the Esprit BTK Scaffold demonstrated comparable safety relative to the respective control at each time point. Several additional studies evaluating the Absorb GT1 BVS are being leveraged to support the safety of the Esprit BTK Scaffold. These safety studies include time points from 12 to 48 months and overlap safety studies (28, 90 days).
Table 5. GLP In Vivo Pharmacokinetics, Degradation, and Safety Studies
| Study Number (Designation) | Animal Model | Number | Follow-up Duration | Endpoints |
| --- | --- | --- | --- | --- |
| Pharmacokinetics | Farm swine | Test: 6 – 7 Esprit BTK Scaffolds per time point Control: N/A | 3 hours, 1, 3, 7, 14, 28, 60, and 90 days | Characterization of in vivo pharmacokinetics: drug release, blood and tissue drug concentrations |
| Pharmacokinetics | Farm swine | Test: 6 – 7 Absorb scaffolds per time point Control: N/A | 3 hours, 1, 3, 7, 14, 28, 60, 90, 120, 180, and 300 days | Characterization of in vivo pharmacokinetics: drug release, blood and tissue drug concentrations |
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| Study Number (Designation) | Animal Model | Number | Follow-up Duration | Endpoints |
| --- | --- | --- | --- | --- |
| Polymer Degradation | Farm swine | Test: 12 Absorb scaffolds
Control: N/A | 28 days | Characterization of in vivo degradation profile with respect to Mn, mass loss, and PDI |
| Polymer Degradation | Farm swine | Test: 12 (90 days), 14 (180 days) Absorb scaffolds per time point
Control: N/A | 90, 180 days | Characterization of in vivo degradation profile with respect to Mn, mass loss, and PDI |
| Polymer Degradation | Yucatan mini-swine | Test: 8 -12 Absorb scaffolds per time point
Control: N/A | 12, 18, 24, 30, 36, and 42 months | Characterization of in vivo degradation profile with respect to Mn, mass loss, and PDI |
| Safety | Farm swine | Test: 10 Esprit BTK Scaffolds
Control: 7 XIENCE Alpine stents (P110019/S070) | 28 days | • Systemic (morbidity, mortality)
• Quantitative coronary angiography
• Optical coherence tomography
• Histomorphology
• Endothelialization by SEM
• Histomorphometry |
| Safety | Farm swine | Test: 10 Esprit BTK Scaffolds
Control: 8 Absorb scaffolds | 90 days | • Systemic (morbidity, mortality)
• Quantitative coronary angiography
• Optical coherence tomography
• Histomorphology
• Endothelialization by SEM
• Histomorphometry |
| Safety | Farm swine | Test: 10 Esprit BTK Scaffolds
Control: 8 Absorb scaffolds | 180 days | • Systemic (morbidity, mortality)
• Quantitative coronary angiography
• Optical coherence tomography
• Histomorphology
• Endothelialization by SEM
• Histomorphometry |
| Safety | Yucatan mini-swine | Test: 12 – 21 Absorb scaffolds | 12, 18, 24, 30, 36, 42, and 48 months | • Systemic (morbidity, mortality)
• Quantitative coronary angiography
• Histomorphology |
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| Study Number (Designation) | Animal Model | Number | Follow-up Duration | Endpoints |
| --- | --- | --- | --- | --- |
| | | Control: 7 – 13
XIENCE V
stents
(P070015) | | · Endothelialization by SEM
(Histomorphometry, OCT, IVUS) |
| Overlapping safety | Farm swine | Test: 12 pairs
Absorb scaffolds
Control: 8 pairs
XIENCE V
stents | 28 days | · Systemic (morbidity, mortality)
· Quantitative coronary angiography
· Histomorphology
· Endothelialization by SEM
(Histomorphometry, OCT) |
| Overlapping safety | Farm swine | Test: 12 pairs
Absorb scaffolds
Control: 9 pairs
XIENCE V
stents | 90 days | · Systemic (morbidity, mortality)
· Quantitative coronary angiography
· Histomorphology
· Endothelialization by SEM
(Histomorphometry, OCT) |
Mn: number average molecular weight; PDI: Polydispersity Index
SEM: Scanning Electron Microscopy; OCT: Optical Coherence Tomography; IVUS: Intravascular Ultrasound
## X. SUMMARY OF PRIMARY CLINICAL STUDY
The applicant performed a clinical study (LIFE-BTK) to establish a reasonable assurance of safety and effectiveness of the revascularization procedure with the Esprit BTK System for the treatment of narrowed infrapopliteal lesions in subjects with chronic limb-threatening ischemia (CLTI) in the US, Singapore, Hong Kong, Taiwan, Australia, and New Zealand under IDE G190111. The LIFE-BTK study consists of a prospective, multicenter, single-blinded, randomized controlled trial (LIFE-BTK RCT) and a non-randomized pharmacokinetics sub-study (LIFE-BTK PK). Data from these clinical studies are the basis for the PMA approval decision. The database for this PMA reflects data collected through 1-year follow-up for the RCT and 60-day follow-up for the PK sub-study. Summaries of the LIFE-BTK RCT and the LIFE-BTK PK sub-study are presented below.
## A. Study Design
Subjects were treated between August 18, 2020, and September 14, 2022. The database for this PMA reflected data collected through August 18, 2023, and included 261 subjects. There were 50 investigational sites globally, with at least 50% of subjects enrolled from the United States.
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The LIFE-BTK RCT study is a prospective, multi-center, single-blinded, randomized controlled trial. Subjects were randomized in a 2:1 ratio between Esprit BTK therapy and the control therapy, which was PTA (Percutaneous Transluminal Angioplasty). PTA is the current standard of care for treatment of below-the-knee artery disease in the US.
The primary safety endpoint was freedom from Major Adverse Limb Event (MALE) at 6 months and Peri-Operative Death (POD) at 30 days. The primary effectiveness endpoint was a composite of limb salvage and primary patency at 1 year. The patients will be followed through 5 years.
Core laboratories were used for angiography, duplex ultrasound (DUS), Intravascular Ultrasound (IVUS), Optical Coherence Tomography (OCT), and wound assessment. Adverse events were adjudicated by a Clinical Events Committee (CEC) and a Data and Safety Monitoring Board (DSMB) reviewed cumulative data from the clinical investigation at regular intervals.
1. Clinical Inclusion and Exclusion Criteria
Enrollment in the LIFE-BTK RCT was limited to subjects who met the following key general inclusion criteria.
General Inclusion Criteria
1. Subject has symptomatic Critical Limb Ischemia (CLI), Rutherford Becker Clinical Category 4 or 5.
2. Subject requires primary treatment of up to two de novo or restenotic (treated with prior PTA) infrapopliteal lesions.
3. Subject must be at least 18 years of age.
4. Female subject of childbearing potential should not be pregnant and must be on birth control.
Anatomic Inclusion Criteria
1. Up to two native infrapopliteal lesions, each lesion located in separate infrapopliteal vessel in the same limb. Restenotic (from prior PTA) lesions are allowed.
a. Lesion must be located in the proximal 2/3 of native infrapopliteal vessels, with vessel diameter of ≥ 2.5 mm and ≤ 4.00 mm by investigator visual assessment.
b. The total scaffold length among all target lesions must not exceed 170 mm.
c. The target vessel cannot have any other angiographic significant lesions ≥50%).
d. Tandem lesions are allowed if they are < 3 cm apart and the total scaffold length used to cover the entire diseased segment is ≤ 170 mm. Each tandem lesion is considered one lesion.
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2. Target lesion(s) must have ≥ 70% stenosis, per visual assessment at the time of the procedure.
3. The distal margin of the target lesion must be located ≥ 10 cm proximal to the proximal margin of the ankle mortise. The vessel segment distal to the target lesion must be patent all the way to the ankle, with no significant lesion (≥ 50% stenosis).
4. Significant lesion (≥ 50% stenosis) in the inflow artery(ies) must be treated successfully (as per physician’s assessment of the angiography) through standard of care prior to the treatment of the target lesion. Treatment can be done within the same trial procedure.
5. Non-target lesion(s) (if applicable) must be located in separate infrapopliteal vessel(s) from the target lesion, and suitable to be treated per institution standard of care.
6. Guidewire must cross the target lesion successfully. Crossing in an antegrade fashion is preferred, but retrograde crossing may be used. However, the treatment must be delivered antegrade.
Subjects were not permitted to enroll in the LIFE-BTK RCT if they met any of the key following exclusion criteria.
## General Exclusion Criteria
1. Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation follow-up period.
2. Subject has had any amputation to the ipsilateral extremity other than the toe or forefoot, or subject has had major amputation to the contralateral extremity < 1 year prior to index procedure and is not independently ambulating.
3. Subject has known hypersensitivity or contraindication to device material and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid) and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoropolymers that cannot be adequately pre-medicated. Subject has a known contrast sensitivity that cannot be adequately pre-medicated.
4. Subject has known allergic reaction, hypersensitivity or contraindication to aspirin; or to ADP antagonists such clopidogrel, prasugrel or ticagrelor; or to anticoagulants such as heparin or bivalirudin, and therefore cannot be adequately treated with study medications. Subject with planned surgery or procedure necessitating discontinuation of antiplatelet medications, within 12 months after index procedure. Planned amputation that will necessitate discontinuation of antiplatelet medications is allowed.
5. Subject has life expectancy ≤ 1 year.
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6. Subject has had a stroke within the previous 3 months with residual Rankin score of $\geq 2$.
7. Subject has renal insufficiency as defined as an estimated GFR < 30 ml/min per $1.73\mathrm{m}^2$.
8. Subject is currently on dialysis.
9. Subject has platelet count < 100,000 cells/mm³ or > 700,000 cells/mm³, a WBC < 3,000 cells/mm³, or hemoglobin < 9.0 g/dl.
10. Subject has known serious immunosuppressive disease (e.g., human immunodeficiency virus), or has severe autoimmune disease, that requires chronic immunosuppressive therapy (e.g., systemic lupus erythematosus, etc.), or subject is receiving immunosuppression therapy for other conditions. Subjects treated for HIV (Human Immunodeficiency Virus) and who have undetectable viral load, such that their immune system is not considered compromised, are eligible.
11. Subject has Body Mass Index (BMI) < 18.
12. Subject is receiving or scheduled to receive anticancer therapy for malignancy within 6 months prior to index procedure or within 1 year after the procedure. Patients taking medications classified as chemotherapy but who have been in remission for at least 6 months are eligible.
13. Subject has coagulation disorder that increases the risk of arterial thrombosis. Subjects with deep vein thrombosis and disorders that increase the risk of deep vein thrombosis can be included in the study.
14. Subject who requires thrombolysis as a primary treatment modality or requires other treatment for acute limb ischemia of the target limb.
15. Subject has previously had, or requires surgical revascularization involving any vessel of the ipsilateral extremity. Prior femoropopliteal or aortobifemoral bypass is allowed. Any bypass to the tibial arteries is not allowed.
16. Subject has signs or symptoms of advanced limb infection or septicemia (fever > 38.5, WBC > 15,000 cells/microliter, hypotension) at the time of assessment. Osteomyelitis of the phalanges or metatarsal heads (as described in exclusion criteria #21a) or cellulitis of the foot amenable to treatment with IV antibiotics at the time of revascularization is acceptable.
17. Subject is bedridden or unable to walk (with assistance is acceptable). Subjects in wheelchair who are able to mobilize on their own can be enrolled.
a. Subject with extensive tissue loss salvageable only with complex foot reconstruction or non-traditional transmetatarsal amputations [1] This
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includes subjects with Osteomyelitis that extends proximal to the metatarsal heads. Osteomyelitis limited to the phalanges or metatarsal heads is acceptable for enrollment.
b. Gangrene involving the plantar skin of the forefoot, midfoot, or heel
c. Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the forefoot, midfoot, or heel
d. Full thickness heel ulcer with/without calcaneal involvement
e. Any wound with calcaneal bone involvement
f. Wounds that are deemed to be neuropathic or non-ischemic in nature
g. Wounds that would require flap coverage or complex wound management for large soft tissue defect
h. Full thickness wounds on the dorsum of the foot with exposed tendon or bone.
18. Subject is unable or unwilling to provide written consent prior to enrollment.
19. Subject has active symptoms and/or a positive test result of COVID-19 or other rapidly spreading novel infectious agent within the prior 2 months.
## Anatomic Exclusion Criteria
1. Lesions with severe calcification, in which there is a high likelihood that successful pre-dilatation cannot be achieved.
2. Lesion that has prior metallic stent implant.
3. Significant (≥ 50% stenosis) lesion in a distal outflow artery that would be perfused by the target vessel and that requires treatment at the time of the index procedure.
4. Subject has had or will require treatment in any vessel with an everolimus drug-coated or drug-eluting device < 30 days pre-study procedure, or during the index procedure, such that the cumulative (Esprit BTK plus everolimus-eluting device) everolimus drug dose exceeds 1790 µg.
5. Target or (if applicable) non-target vessel contains visible thrombus as indicated in the angiographic images.
6. Subject has angiographic evidence of thromboembolism or atheroembolism in the ipsilateral extremity. (Pre- and post-angiographic imaging must confirm the absence of emboli in the distal anatomy.)
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7. Unsuccessfully treated proximal inflow limiting arterial stenosis or inflow-limiting arterial lesions left untreated.
8. No angiographic evidence of a patent pedal artery.
9. Target or (if applicable) non-target lesion location requiring bifurcation treatment method that requires scaffolding of both branches (provisional treatment, without intention of scaffolding both branches is acceptable).
10. Aneurysm in the iliac, common femoral, superficial femoral, popliteal or target artery of the ipsilateral extremity.
11. Visual assessment of the target lesion suggests that the investigator is unable to pre-dilate the lesion according to the vessel diameter.
12. Target lesion has a high probability that atherectomy will be required at the time of index procedure for treatment of the target vessel.
## 2. Follow-up Schedule
All subjects were scheduled to return for follow-up examinations at 30 days, 3 months, 6 months, and 1 year, and will be continued annually to complete 5 years of follow-up. Additional follow-ups, for subjects presenting with wounds at the time of the index procedure, occurred at 14 days and 42 days.
Preoperatively, laboratory, functional status (RB category), and wound (if applicable) assessments, as well as ABI/TBI (Ankle Brachial Index/Toe Brachial Index) measurement, were conducted to determine subject eligibility. Anatomical eligibility was confirmed at the time of the index procedure, prior to randomization.
Postoperatively, the objective parameters measured during the study included the following key assessments: ABI/TBI measurement, functional status RB assessment, index wound assessment, and DUS. Adverse events and complications are recorded at all visits except the 14-day and 42-day visits.
The key time points are shown in Table 6 below and are included in the tables summarizing safety and effectiveness.
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Table 6. Study Event Schedule Procedure and Assessments
| PROCEDURE/TEST | Baseline (within 30 days prior to index procedure) | Pre-Procedure (within 24 hours) | Procedure | Post-Procedure | 14 days (± 3 d) office visit/ remote index wound image* | 30 days (± 7 d) office visit* | 30 days (± 14 d) office visit* | 42 days (± 7 d) office visit/ remote index wound image* | 90 days (± 14 d) office visit* | 180 days (± 28 d) office visit* | 1 yr (± 28 d) office visit* | 2yrs (± 28 d) office visit* | 3 yrs (± 28 d) office visit* | 4 yrs (± 28 d) office visit* | 5 yrs (± 28 d) office visit* | Unscheduled visits |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Vascular Angiogram, IVUS^{1} | ✓ | | ✓ | | | | | | | | | | | | | ✓ |
| Duplex Ultrasound^{2} | | | | | | | ✓ | | | ✓ | ✓ | ✓ | ✓ | | | ✓ |
| ABI/TBI measurement^{3} | ✓ | ✓ | | | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
| Study device information | | | ✓ | | | | | | | | | | | | | |
| Per Protocol Medications | | ✓ | ✓ | ✓ | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
| Concomitant Medications | ✓ | | ✓ | ✓ | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
| Adverse Events | | | ✓ | ✓ | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
| Patient Reported Outcome Instruments (WIQ, PAQ, EQ-5D-5L) | ✓ | | | | | ✓ | | | ✓ | ✓ | ✓ | | | | | |
| Rutherford Becker category assessment | ✓ | | | | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
| Index wound assessment^{4} | ✓ | | | ✓ | ✓ | ✓ | | ✓ | ✓ | ✓ | ✓ | | | | | ✓ |
| New wound assessment^{5} | | | | | | ✓ | | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
1 Angiogram to confirm eligibility criteria can be done within 30 days prior to index procedure or during the procedure, as long as it is carried out prior to randomization of the patient. IVUS should only be captured if it is the standard-of-care of the site PI to use IVUS in his/her patients in this population.
2 Duplex ultrasound is required at 30 days ± 14 days post-procedure, at 180 days, and at 1, 2 and 3 years; if a patient is symptomatic or occlusion is suspected, duplex as well as angiogram should be completed. Additionally, a duplex ultrasound must be completed within 30 days (±14 days) post-reintervention to the index limb.
3 While ABI/TBI measurement is listed at both "baseline" and "pre-procedure" time points, this measurement only needs to occur once before the procedure (either at baseline or at pre-procedure time point).
4 Index wound needs to be assessed before the procedure to confirm patient eligibility (ischemic arterial wound). If the picture of the wound was taken within 7 days prior to index procedure, the picture does not need to be repeated the day of index procedure. If the picture was taken > 7 days prior to index procedure, a second picture must be taken the day of index procedure and can be taken up to 24 hours post-procedure. In cases where picture is taken on the day of index procedure, baseline will be defined as "within 24 hours post-procedure". Index wound assessment for healing and infection will be assessed by the core laboratory through 90 days (14 days, 30 days, 42 days and 90 days). For index wounds that are not healed by 90 days, the index wound will be assessed by the core laboratory at 180 days. If the index wound is not healed by 180 days, index wound assessment by the core laboratory will be carried out at 1 year. Index wounds that have healed by 90 days will not be assessed by the core laboratory at 180 days and 1 year. A formal office visit is highly recommended at 14-day and 42-day follow-up for evaluation of index wound. The option to take wound pictures remotely at 14 days and 42 days in accordance to the core laboratory wound imaging guidelines is for subjects that are unable to complete an office visit. No wound images will be collected outside of the protocol defined timepoints.
5 New wound is defined as wound below the knee in the index limb that was not identified at the time of the index procedure or wound that has recurred in the same location following the healing of the index wound. The new wound will be assessed firstly by the wound assessment core laboratory for etiology. Subsequently, the new wound will be evaluated by the site per protocol until the wound is healed through the 5-year follow-up. If a new wound is first observed at 5-year follow-up, a picture will be taken for etiology assessment by the core laboratory. As this will be the final patient visit for the trial, no additional pictures of the new wound will be required following the initial picture submitted to the core laboratory. The 14-day and 42-day visits are not required for subjects with new wounds.
* To aid in follow-up compliance, if necessary, an independent service may be utilized to provide in-home visits for clinical follow-up.
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# 3. Clinical Endpoints
With regards to safety, the primary safety endpoint was freedom from Major Adverse Limb Event (MALE) at 6 months + Peri-Operative Death (POD) at 30 days. MALE includes above-ankle amputation in index limb and major re-intervention on index limb at 6 months, and POD includes perioperative mortality at 30 days. Major re-intervention includes the creation of a new bypass graft, bypass graft revision, the use of thrombectomy, or thrombolysis related to the target lesion. The hypothesis test is designed to show non-inferiority of Esprit BTK arm to PTA arm with a one-sided alpha of 0.025. The null $(\mathrm{H}_0)$ and alternative $(\mathrm{H}_1)$ hypotheses are:
$$
\mathrm{H}_0: q_{BTK} - q_{PTA} \leq \delta
$$
$$
\mathrm{H}_1: q_{BTK} - q_{PTA} > \delta
$$
where $q_{BTK}$ and $q_{PTA}$ are the primary safety endpoint rates for the Esprit BTK arm and PTA arm, respectively. The non-inferiority margin of $\delta$ is set at -0.1 (-10%).
With regards to effectiveness, the primary effectiveness endpoint was a composite of limb salvage and primary patency at 1 year. It included freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel, binary restenosis of target lesion, and clinically-driven target lesion revascularization (CD-TLR). Binary restenosis was defined as the presence of a hemodynamically significant restenosis >50% by angiography, or Peak Systolic Velocity Ratio (PSVR) ≥ 2.0 by duplex ultrasound. In the presence of abnormal reference Peak Systolic Velocity (PSV), the duplex ultrasound core laboratory used additional secondary criteria (correlating factors) to identify target lesion stenoses >50% in severity. Target lesion revascularization (TLR) is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. Bailout with metallic stent, in either study arm, due to acute closure or to achieve <30% stenosis during index procedure will be considered a CD-TLR.
The hypothesis test is designed to show superiority of Esprit BTK arm to PTA arm with a one-sided alpha of 0.025. The null $(\mathrm{H}_0)$ and alternative $(\mathrm{H}_1)$ hypotheses are:
$$
\mathrm{H}_0: P_{BTK} - P_{PTA} \leq 0
$$
$$
\mathrm{H}_1: P_{BTK} - P_{PTA} > 0
$$
where $P_{BTK}$ and $P_{PTA}$ are the primary effectiveness endpoint rates for the Esprit BTK arm and PTA arm, respectively.
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The primary safety endpoint and primary effectiveness endpoint were evaluated when all subjects had completed their 1-year visit. The primary safety endpoint was tested for non-inferiority of Esprit BTK arm to PTA arm. The primary effectiveness endpoint was tested for the superiority of Esprit BTK arm as compared to PTA arm.
Both primary analyses must pass for the trial to be successful.
The primary effectiveness endpoint was modified during the trial to add binary restenosis and change the timepoint from 6 to 12 months. To account for the change in definition, LIFE-BTK RCT also included the original composite primary effectiveness endpoint as one of the two powered secondary endpoints analyzed at 1 year:
- Binary restenosis of the target lesion
- A composite endpoint of freedom from above ankle amputation of the index limb, total occlusion of the target vessel and CD-TLR.
Additionally, index wound measurements and assessment for healing and infection over time were performed by a wound core laboratory. Assessment of new wounds (i.e., wound that was not present at baseline) for etiology was also performed by the core laboratory at the time of first identification. New wound progression was then assessed by the site.
## B. Accountability of PMA Cohort (RCT Group)
In LIFE-BTK, a total of 261 subjects (Esprit BTK: 173; PTA:88) were randomized at 50 investigational sites, between August 18, 2020, and September 14, 2022. A total of 179 target lesions were treated in the Esprit BTK arm, and 92 lesions in the PTA arm. Early termination at 1 year, due to lost-to-follow-up, consent withdrawal or death, occurred in 11.6% (20/173) of the subjects in the Esprit BTK arm and 11.4% (10/88) in the PTA arm. The final 1-year follow-up visit for the RCT group occurred on August 17, 2023. The details on subject disposition for intent-to-treat (ITT) population and as-treated (AT) population are presented in Figure 3 and Figure 4 respectively.
At 6 months, there were 244 subjects active in the trial. For the evaluation of the primary safety endpoint, if a subject had a safety endpoint event prior to termination, this subject is included in the analysis, or if the terminated subject had no status prior to the lower limit of the 6-month follow-up window, the subject was excluded. At the time of database snapshot, of the 261 subjects enrolled in LIFE-BTK RCT, data on 245 subjects were available for evaluation of the primary safety endpoint at 6 months².
At 1 year, there were 231 subjects active in the trial. If a subject had an effectiveness endpoint event prior to termination, this subject is included in the analysis. For the evaluation of the effectiveness endpoint, if a subject did not have imaging information (either DUS or angiography) to confirm vessel patency status at 1-year, the subject was
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excluded from the analysis unless they had an effectiveness endpoint event earlier. At the time of database snapshot, based on the above rules, data on 220 subjects were available for the evaluation of the primary effectiveness endpoint at 1 year.
Figure 3: Subject disposition flow chart – Intent-to-Treat Population
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Figure 4: Subject disposition flow chart - As-Treated Population
Note: In the Esprit BTK arm, there were 2 subjects who expired within 30 days post-procedure. These 2 subjects are not counted at the 6-month follow-up on this chart, but they are included in the primary safety endpoint analysis in Table 9. Therefore, the total number of evaluable subjects of the Esprit BTK arm for the primary safety endpoint at 6 months was 160 (and not 158 as shown on this flowchart).
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In the PTA arm, one subject was withdrawn (as lost-to-follow-up) at day 281 post-procedure. However, the last contact information of the subject in the study was 90 days post-index procedure which was prior to the beginning of the 6-month follow-up windows (180 days - 28 days = 152 days). Therefore, the subject was not included in the primary safety endpoint analysis since there was no information on the status of the subject. This subject is included in the total of 86 active PTA subjects at 6-month follow-up as shown in the flowchart. However, this subject did not have any known endpoint event prior to withdrawal and therefore was excluded from the analysis in Table 9.
## C. Study Population Demographics and Baseline Parameters
The key baseline demographics and risk factors for the LIFE-BTK RCT population are presented in Table 7. The demographics of the study population are typical for a CLTI study, and 80.1% of the subjects were enrolled in the US and 19.9% outside of US. All baseline characteristics were well balanced with no statistical differences between the study arms.
The mean ages were 73.3 ± 9.9 and 71.1 ± 10.4 years in the Esprit BTK and PTA arms, respectively. Over one-third of subjects in both arms were female. Out of the total registered population, 59% were identified as white and 41% as non-white, with 16.5% of the total population identified as Hispanic ethnicity. Mean body mass index values were 27.85 ± 5.47 and 28.94 ± 5.77 kg/m² in the Esprit BTK and PTA arms, respectively. Rutherford Becker (RB) Category in both arms was about evenly split between RB 4 and RB 5 and, hence, half of the population in both arms had wound(s) on the index limb at baseline.
Risk factors had a high prevalence in both arms, including diabetes (~70%), hypertension (90-95%), and hyperlipidemia (~80%). About half of the subjects in both arms were tobacco users, one-third of the population had previous percutaneous or surgical coronary revascularization, and about 60% in both arms had multi-vessel peripheral vascular disease. There were no significant differences between the Esprit BTK and PTA arms in baseline characteristics.
Table 7. Baseline Demographics and Medical History (Intent-to-Treat Population)
| | Esprit BTK
(N=173) | PTA
(N=88) |
| --- | --- | --- |
| DEMOGRAPHICS | | |
| Age (Year) | | |
| Mean ± SD (n) | 73.3 ± 9.9 (173) | 71.1 ± 10.4 (88) |
| Range (min, max) | (47, 94) | (49, 92) |
| Gender | | |
| Male | 67.6% (117/173) | 69.3% (61/88) |
| Female | 32.4% (56/173) | 30.7% (27/88) |
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| | Esprit BTK (N=173) | PTA (N=88) |
| --- | --- | --- |
| Race | | |
| White | 56.6% (98/173) | 63.6% (56/88) |
| American Indian or Alaska Native | 0.0% (0/173) | 1.1% (1/88) |
| Asian | 20.8% (36/173) | 12.5% (11/88) |
| - Chinese | 77.8% (28/36) | 100.0% (11/11) |
| - South Asian | 16.7% (6/36) | 0.0% (0/11) |
| - Other | 5.6% (2/36) | 0.0% (0/11) |
| Black or African American | 12.1% (21/173) | 12.5% (11/88) |
| Native Hawaiian or Other Pacific Islander | 0.6% (1/173) | 2.3% (2/88) |
| Declined or unable to disclose | 10.4% (18/173) | 8.0% (7/88) |
| Ethnicity | | |
| Hispanic | 17.9% (31/173) | 13.6% (12/88) |
| Non-Hispanic | 76.3% (132/173) | 79.5% (70/88) |
| Declined or unable to disclose | 5.8% (10/173) | 6.8% (6/88) |
| BMI | | |
| Mean ± SD (n) | 27.85 ± 5.47 (173) | 28.94 ± 5.77 (88) |
| Range (min, max) | (18.0, 49.6) | (18.6, 45.9) |
| RISK FACTORS | | |
| Tobacco Use | 52.6% (91/173) | 53.4% (47/88) |
| Hypertension | 94.2% (163/173) | 90.9% (80/88) |
| Hyperlipidemia | 80.9% (140/173) | 81.8% (72/88) |
| Diabetes Mellitus | 71.1% (123/173) | 69.3% (61/88) |
| MEDICAL HISTORY and PRESENTATION | | |
| History of Peripheral Artery Disease | 82.7% (143/173) | 77.3% (68/88) |
| Multi-vessel Peripheral Vascular Disease | 62.5% (105/168) | 61.2% (52/85) |
| Previous Amputation to Target Limb | 9.2% (16/173) | 8.0% (7/88) |
| Cardiac History | | |
| - Prior Myocardial Infarction | 16.9% (27/160) | 14.8% (13/88) |
| - Previous Percutaneous or Surgical | 34.7% (59/170) | 35.6% (31/87) |
| Coronary Revascularization | | |
| - Congestive Heart Failure | 19.4% (33/170) | 19.3% (17/88) |
| Neurologic and Renal History | | |
| - Cerebrovascular Disease | 13.2% (22/167) | 17.4% (15/86) |
| - Prior Cerebrovascular Accident (CVA) or Stroke | 11.7% (20/171) | 17.0% (15/88) |
| - Transient ischemic attack | 3.5% (6/170) | 2.3% (2/87) |
| - Renal Disease | 15.8% (27/171) | 16.3% (14/86) |
| Rutherford Becker Category | | |
| - RB4 | 52.0% (90/173) | 51.1% (45/88) |
| - RB5 | 48.0% (83/173) | 48.9% (43/88) |
| ABI of Target Limb, Mean ± SD (n) | 0.87 ± 0.32 (150) | 0.91 ± 0.33 (77) |
| TBI of Target Limb, Mean ± SD (n) | 0.51 ± 0.31 (50) | 0.46 ± 0.24 (29) |
| Wound on Target Limb at Baseline | 49.1% (85/173) | 51.1% (45/88) |
N: Total number of subjects. n: Number of subjects with available data for variable of interest
Data presented as $\% (\mathrm{n} / \mathrm{N})$ or Mean $\pm$ standard deviation
BMI: Body Mass Index; ABI: Ankle Brachial Index; TBI: Toe Brachial Index
Baseline target lesion characteristics, procedural and post-procedural information are presented in Table 8. There were a total of 179 target lesions in 173 subjects in the Esprit BTK arm, and 92 target lesions in 88 subjects in the PTA arm. The largest number of
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target lesion segments were located in the anterior tibial artery (AT), with $34.3\%$ (59/172) and $27.0\%$ (24/89) in the Esprit BTK arm and PTA arm, respectively. The mean lesion length ( $\sim 44\mathrm{mm}$ ) and mean reference vessel diameter ( $\sim 2.9\mathrm{mm}$ ) were similar between the arms. The mean pre-procedure percentage of diameter stenosis ( $\% \mathrm{DS}$ ) was $72.6 \pm 18.9\%$ in the Esprit BTK arm and $73.7 \pm 21.0\%$ in the PTA arm. At post-procedure, the mean in-device and in-segment $\% \mathrm{DS}$ were numerically lower in the Esprit BTK arm compared to the PTA arm. The Esprit BTK arm also achieved a higher percentage of final diameter ( $\% \mathrm{DS}$ ) $< 30\%$ at the rate of $95.9\%$ (163/170), compared to the PTA arm which had a rate of $72.6\%$ (61/84).
Table 8. Baseline, Procedure and Post-Procedure Target Lesion Characteristics (Intent-to-Treat Population)
| | Esprit BTK (N=173) (L=179) | PTA (N=88) (L=92) |
| --- | --- | --- |
| Baseline Angiographic Core Laboratory Reported Lesion Characteristics | | |
| Artery Segment | | |
| - Anterior Tibial | 34.3% (59/172) | 27.0% (24/89) |
| - Posterior Tibial | 15.1% (26/172) | 18.0% (16/89) |
| - Peroneal | 16.3% (28/172) | 23.6% (21/89) |
| - Tibioperoneal Trunk | 15.1% (26/172) | 16.9% (15/89) |
| - Tibioperoneal Trunk – Posterior Tibial | 8.7% (15/172) | 9.0% (8/89) |
| - Tibioperoneal Trunk – Peroneal | 10.5% (18/172) | 5.6% (5/89) |
| Lesion Length (mm) | | |
| Mean ± SD (l) | 43.78 ± 31.84 (172) | 44.75 ± 29.07 (89) |
| Range (min, max) | (3.82, 148.40) | (5.33, 125.10) |
| Reference Vessel Diameter Pre-intervention | | |
| Mean ± SD (l) | 2.94 ± 0.77 (147) | 2.82 ± 0.74 (80) |
| Range (min, max) | (1.37, 5.23) | (1.35, 4.79) |
| Calcification | | |
| None | 99.4% (171/172) | 100.0% (89/89) |
| Moderate | 0.6% (1/172) | 0.0% (0/89) |
| Thrombus | | |
| Absent | 100.0% (172/172) | 100.0% (89/89) |
| Ulceration | 0.0% (0/172) | 0.0% (0/89) |
| Aneurysm | 0.0% (0/172) | 0.0% (0/89) |
| TASC II Type | | |
| A | 48.3% (83/172) | 52.8% (47/89) |
| B | 35.5% (61/172) | 25.8% (23/89) |
| C | 16.3% (28/172) | 21.3% (19/89) |
| D | 0.0% (0/172) | 0.0% (0/89) |
| % Diameter Stenosis (DS) Pre-intervention | | |
| Mean ± SD (l) | 72.6 ± 18.9 (172) | 73.7 ± 21.0 (89) |
| Range (min, max) | (23, 100) | (18, 100) |
| Total Occlusion at Treatment Site | 15.1% (26/172) | 20.2% (18/89) |
| Angiographic Core Laboratory Reported Post-Procedure Measurements | | |
| Residual %DS after Pre-dilatation/PTA | | |
| Mean ± SD (l) | 30.0 ± 12.6 (84) | 25.0 ± 8.7 (3) |
| Range (min, max) | (3, 61) | (15, 31) |
| Post-procedure In-Device %DS | | |
| Mean ± SD (l) | 13.1 ± 8.2 (170) | 21.8 ± 11.4 (84) |
| Range (min, max) | (-9, 35) | (-7, 48) |
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| | Esprit BTK
(N=173)
(L=179) | PTA
(N=88)
(L=92) |
| --- | --- | --- |
| Post-procedure In-Segment %DS
Mean ± SD (l)
Range (min, max) | 17.0 ± 9.3 (170)
(-6, 60) | 22.8 ± 11.2 (84)
(-5, 48) |
| Final Diameter Stenosis < 30% | 95.9% (163/170) | 72.6% (61/84) |
| Residual Dissection Post-Intervention | 0.0% (0/170) | 0.0% (0/84) |
| Procedural Characteristics (Site-Reported) | | |
| Pre-dilation Performed | 100.0% (179/179) | 100.0% (92/92) |
| Scaffold Post-dilated Without Complications | 99.4% (176/177) | NA |
| Metal Stent Bailout | 0.0% (0/173) | 5.7% (5/88) |
N: number of subjects. L: Total number of target lesions. : Number of target lesions with available data for variable of interest
Data presented as % (l/L) or Mean ± standard deviation.
The procedural endpoints for technical and device success are described in Table 9. Technical Success is defined on a per lesion basis as the attainment of a final residual stenosis of < 30% at the intended target lesion(s) following use of the study device(s). Standard pre-dilatation catheters and post-dilatation catheters (if applicable) may be used. Bailout at lesion level does not impact technical success if the above criteria are met. Measurements of % diameter stenosis for technical success were per angiographic core laboratory. Device success is defined on a per device basis, as the achievement of successful delivery and deployment of the study device(s) at the intended target lesion and successful withdrawal of the delivery catheter.
Table 9. Procedural Endpoints
| | Esprit BTK
(N = 173)
(L = 179)
(D = 356) | PTA
(N = 88)
(L = 92) | Difference
[95% CI]1 |
| --- | --- | --- | --- |
| Technical Success | 95.9% (163/170) | 72.6% (61/84) | 23.26% [13.91%, 33.84%] |
| Device Success | 95.2% (339/356) | N/A | N/A |
1 By Newcombe score method. The confidence interval was calculated without any multiplicity adjustment.
N: Total number of subjects. L: Number of target lesions. D: Number of devices. NA: Not applicable.
## D. Safety and Effectiveness Results
### 1. Safety Results
The analysis of safety was based on the as-treated population (AT) of 260 subjects. Data on a total of 245 subjects were available for the evaluation of the primary safety endpoint at 6 months post-procedure. The key safety outcomes for this study are presented below in Table 10, and in Figure 5. Adverse effects are reported in Table 11 and Table 12.
As shown in Table 10, the primary safety endpoint was met (p-value = 0.0019). The individual components of the primary safety endpoint are presented in Table 10, in a non-hierarchical fashion. A total of 5 events in 5 subjects occurred in the Esprit BTK
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arm, and none in the PTA arm. These events were two peri-operative deaths, two above ankle amputations and one major re-intervention on the index limb. All 5 events were assessed by the investigator as not related to the study procedure and not related to the study device.
Table 10. Primary Safety Endpoint
| Primary Safety Endpoint As-Treated (AT) (N=260) | Esprit BTK (N=170) | PTA (N=90) | Difference (One Sided Lower 97.5% CL)¹ | P-value² |
| --- | --- | --- | --- | --- |
| Freedom from MALE³ at 6 months and POD at 30 days | 96.9% (155/160) | 100.0% (85/85) | -3.13% (-7.11%) | 0.0019 |
| Components | Esprit BTK | PTA | Difference [95% CI]¹ | - |
| Freedom from Major Adverse Limb Events…
---
**Source:** [https://fda.innolitics.com/device/P230036](https://fda.innolitics.com/device/P230036)
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