Indications, safety and warnings for ENROUTE^™ Transcarotid Neuroprotection System

The ENROUTE Enflate Transcarotid RX Balloon Dilatation Catheter is intended for percutaneous transluminal angioplasty and post-dilatation of self-expanding stents in the carotid arteries.

The ENROUTE Enflate Transcarotid RX Balloon Dilatation Catheter is contraindicated for use in coronary arteries. Generally, further contraindications include, but may not be limited to:

• Patients with highly calcified lesions resistant to PTA.
• Patients with a target lesion with a large amount of adjacent acute or sub acute thrombus.
• Patients with uncorrected bleeding disorders.
• Patients that have not been anti-coagulated.

• Only physicians who have received appropriate training and are familiar with the principles, clinical applications, complications, side effects and hazards commonly associated with carotid interventional procedures should use this device.
• Do not use the balloon if there are any abnormalities in the sterile barrier (e.g. broken seal, torn or breached barrier) or the product.
• The device is provided sterile and for single use only. Do not resterilize and/or reuse it, as this can potentially result in compromised device performance and increased risk of crosscontamination which in turn, may result in patient injury, illness or death.
• Do not expose the device to organic solvents (e.g. alcohol).
• Do not use with Ethiodol or Lipiodol* contrast media. *Ethiodol and Lipiodol are Trademarks of Guerbet SA.
• To reduce the potential for vessel damage or the risk of dislodgement of particles, it is very important that the inflated diameter of the balloon should approximate the diameter of the vessel just proximal and distal to the lesion.
• When the balloon catheter is exposed to the vascular system, it should be manipulated while under high-quality fluoroscopic observation. Do not advance or retract the device unless the balloon is fully deflated under vacuum. If resistance is met during manipulation, determine the cause of the resistance before proceeding. Failure to do so may result in damage to the product or harm to the patient.
• Balloon pressure should not exceed the rated burst pressure. Use of a pressure monitoring device is recommended to prevent over-pressurization.
• To reduce the potential for air embolus into the vessel, use only the recommended balloon inflation medium (a 50/50 mixture by volume of contrast medium and normal saline). Never use air or any gaseous medium to inflate the balloon.

• Caution: Federal (USA) law restricts device to sale by or on the order of a physician.
• Carefully read all instructions prior to use. Observe all warnings and precautions noted throughout these instructions. Failure to do so may result in complications.
• The device should only be used by physicians who are trained in the performance of arteriography and who have received appropriate training in percutaneous transluminal angioplasty in the indicated arteries. PL20950 rev 02 Release Date 11/2022 Page 2 of 8
• Use the balloon prior to the “Use Before” date specified on the package.
• Prior to use, the device should be examined to verify functionality, integrity, and ensure that its size is suitable for the specific procedure. Always inspect the balloon catheter carefully for bends, kinks or other damage prior to insertion.
• Before and during the procedure, appropriate anticoagulant/antiplatelet therapy should be provided to the patient, as needed.
• The minimal acceptable guide catheter/introducer sheath size is printed on the package label. Do not attempt to pass the balloon catheter through a smaller size guide catheter/introducer sheath than indicated on the label. Use of a smaller than indicated accessory device can lead to introduction of air into that device as the balloon catheter is advanced, which may not be removed during air aspiration.
• Caution should be taken when treating patients with poor renal function who, in the physician's opinion, may be at risk for contrast-induced nephropathy.
• Embolic protection is recommended when using the balloon catheter in a carotid angioplasty procedure. If an embolic protection device is used, follow the applicable instructions for use.
• Exposure to X-ray radiation doses to patients and physicians should be limited by using sufficient shielding, reducing fluoroscopy times, and modifying X-ray technical factors when possible.

Potential complications, which may lead to additional intervention, include, but are not limited to:

• Abrupt Closure
• Acute Myocardial Infarction
• Acute vessel closure
• Allergic reaction (device, contrast medium and medications)
• Amputation
• Aneurysm
• Angina
• Arrhythmias (major, minor), including ventricular fibrillation
• Arteriovenous fistula
• Artery spasm
• Coma
• Death
• Drug reactions, allergic reaction to contrast medium
• Embolism
• Hematoma
• Hemorrhage, including bleeding at puncture site
• Hypotension / hypertension
• Infection
• Ischemia
• Necrosis
• Nephropathy
• Neurological events, including peripheral nerve injury and neuropathies
• Organ failure (single, multiple)
• Paralysis
• Pyrogenic reaction
• Renal failure
• Restenosis
• Seizures
• Sepsis / infection / inflammation
• Shock
• Stroke, air embolism and embolization or fragmentation of thrombotic or athlerosclerotic material
• Thrombosis
• Transient Ischemic Attack
• Vascular Complications (e.g. intimal tear, dissection, pseudoaneurysm, perforation, rupture, spasm, occlusion)
• Weakness
• X-ray radiation exposure may cause adverse events including, but not limited to, alopecia, burns, cataracts, or delayed neoplasia (cancers)

The ENROUTE® Transcarotid Stent System used in conjunction with the ENROUTE Transcarotid Neuroprotection System (NPS) is indicated for the treatment of patients at high risk and standard risk for adverse events from carotid endarterectomy, who require carotid revascularization and meet the criteria outlined below:

Use of the ENROUTE Transcarotid Stent System is contraindicated in the following patients:

• Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated.
• Patients in whom the ENROUTE Transcarotid NPS is unable to be placed.
• Patients with uncorrected bleeding disorders.
• Patients with known allergies to nitinol.
• Lesions in the ostium of the common carotid artery.

General Warnings

• Only physicians who have received appropriate training for transcarotid stenting and who are familiar with the principles, clinical applications, complications, side effects and hazards commonly associated with carotid interventional procedures should use this device.
• The safety and efficacy of the ENROUTE Transcarotid Stent System have not been demonstrated with embolic protection systems other than the ENROUTE Transcarotid NPS. Use the ENROUTE Transcarotid Stent System only with the ENROUTE Transcarotid NPS.
• The long term performance (> 3 years) of carotid stents has not yet been established.
• As with any type of vascular implant, infection secondary to contamination of the stent may lead to thrombosis, pseudoaneurysm or rupture.
• The stent may cause a thrombus, distal embolization or may migrate from the site of implant through the arterial lumen. Appropriate sizing of the stent to the vessel is required to reduce the possibility of stent migration (see Section 9.3 of these instructions). In the event of thrombosis of the expanded stent, thrombolysis and PTA should be attempted.
• Overstretching of the artery may result in rupture and life-threatening bleeding.
• In patients requiring the use of antacids and/or H2-antagonists before or immediately after stent placement, oral absorption of antiplatelet agents (e.g., aspirin) may be adversely affected.
• The appropriate antiplatelet and anticoagulation therapy should be administered pre- and post-procedure as suggested in Section 9.1 of these instructions.
• In the event of complications such as infection, pseudoaneurysm or fistulization, surgical removal of the stent may be required.

Patient Selection Warnings
Safety and effectiveness of the ENROUTE® Transcarotid Stent System has NOT yet been established in patients with the characteristics noted below.

• Lesion Characteristics:
  • Patients with evidence of intraluminal thrombus thought to increase the risk of plaque fragmentation and distal embolization.
  • Patients whose lesion(s) may require more than two stents.
  • Patients with total occlusion of the target vessel.
  • Patients with lesions of the ostium of the common carotid.
  • Patients with highly calcified lesions resistant to PTA.
  • Concurrent treatment of bilateral lesions.
• Patient Characteristics
  • Patients at low-to-moderate risk for adverse events from carotid endarterectomy.
  • Patients experiencing acute ischemic neurologic stroke or who experienced a stroke within 48 hours.
  • Patient has had a recent (<7 days) stroke of sufficient size (on CT or MRI) to place him or her at risk of hemorrhagic conversion during the procedure.
  • Patients with ipsilateral intracranial or extracranial arterial stenosis greater in severity than the lesion to be treated, cerebral aneurysm > 5 mm, AVM (arteriovenous malformation) of the cerebral vasculature, or intracranial tumor.
  • Patients with arterio-venous malformations in the territory of the target carotid artery.
  • Patients with bleeding diathesis or coagulopathies.
  • Patients with poor renal function, who, in the physician’s opinion, may be at high risk for a reaction to contrast medium.
  • Patients with perforated vessels evidenced by extravasation of contrast media.
  • Patients with aneurismal dilation immediately proximal or distal to the lesion.
  • Pregnant patients or patients under the age of 18.
• Access Characteristics
  • Patients with known internal carotid artery tortuosity that would preclude the use of catheter-based techniques.
  • Patients with known common carotid or internal carotid artery tortuosity that would preclude the use of catheter-based techniques.
  • Patients in whom common carotid access is not possible.

Risk of distal embolization may be higher if the ENROUTE Transcarotid Stent System cannot be used in conjunction with the ENROUTE Transcarotid NPS during the carotid stenting procedure.

Device Use Warnings

• USE OF A SMALLER THAN INDICATED ACCESSORY DEVICE OTHER THAN THE ENROUTE TRANSCAROTID ARTERIAL SHEATH MAY LEAD TO INTRODUCTION OF AIR INTO THAT DEVICE AS THE STENT DELIVERY SYSTEM IS ADVANCED, WHICH MAY NOT BE REMOVED DURING AIR ASPIRATION.
• Ensure that the catheter system is flushed according to the steps outlined in "Introduction of Stent Delivery System" (Section 9.4). Failure to do so could result in air entering the ENROUTE’s Transcarotid Arterial Sheath.
• Ensure that there is a tight seal between the ENROUTE catheter and the valve for the ENROUTE Transcarotid Arterial Sheath during aspiration. Failure to do so could result in air entering the ENROUTE Transcarotid Arterial Sheath.
• The black dotted pattern on the gray temperature exposure indicator found on the pouch must be clearly visible. DO NOT USE THE PRODUCT IF THE ENTIRE TEMPERATURE EXPOSURE INDICATOR IS COMPLETELY BLACK as the pre-programmed stent diameter may have been compromised.
• Do not use the device if there are abnormalities in the sterile barrier (e.g., broken seal, torn or breached barrier) or the product.
• This device is intended for one-time use only. Do not re-sterilize and/or reuse. Structural integrity and/or function may be impaired through reuse or cleaning.
• Do not use the ENROUTE® Transcarotid Stent System after the “Use By” date specified on the package.
• Do not use with Ethiodol or Lipiodol* contrast media, which may adversely affect the stent delivery system. *Ethiodol and Lipiodol are Trademarks of Guerbet S.A.
• Do not expose the delivery system to organic solvents (e.g., alcohol) as structural integrity and/or function of the device may be impaired.
• The stent is not designed for dragging or repositioning.
• Once the stent is partially deployed, it cannot be recaptured using the stent delivery system.
• As with any type of vascular implant, infection secondary to contamination of the stent may lead to thrombosis, pseudoaneurysm or rupture.
• When multiple stents are used, they should be of similar composition.
• Long-term outcomes following repeat dilatation of endothelialized stents are unknown.

Stent Handling Precautions

• The ENROUTE Transcarotid Stent System is supplied STERILE and is intended for single use only. DO NOT resterilize and/or reuse the device.
• The ENROUTE Transcarotid Stent System is shipped with the Tuohy Borst valve in the OPEN 
• position. Care should be taken not to pre-deploy the stent. The device should be prepped in the tray. (See Section 9.3 of these instructions).
• Do not use the ENROUTE Transcarotid Stent System after the "Use By" date specified on the package.
• Do not use if the pouch is opened or damaged.
• Store in a cool, dark, dry place.

Stent Placement Precautions

• Venous access should be available during carotid stenting in order to manage bradycardia and/or hypotension either by pharmaceutical intervention or placement of a temporary pacemaker, if needed.
• When catheters are in the body, they should be manipulated only under fluoroscopy. Radiographic equipment that provides high quality images is needed.
• The delivery system is not designed for the use of power injection. Use of power injection may adversely affect device performance.
• If resistance is met during delivery system introduction, the system should be withdrawn and another system used.
• Prior to stent deployment, remove all slack from the catheter delivery system (see Section 9.4, 4 of these instructions).
• Adequate distance must be maintained from the distal tip of the transcarotid access sheath and the proximal edge of the stent to avoid stent delivery within the lumen of the sheath.
• When treating multiple lesions, the distal lesion should be initially stented, followed by stenting of the proximal lesion. Stenting in this order obviates the need to cross the proximal stent in placement of the distal stent and reduces the chance for dislodging stents that have already been placed.
• Overlap of sequential stents is necessary, but the amount of overlap should be kept to a minimum (approximately 5 mm). In no instance should more than 2 stents overlap.
• Fractures of this stent may occur. Fractures may also occur with the use of multiple overlapping stents. Fractures have been reported most often in clinical uses for which the safety and effectiveness have not been established. The causes and clinical implications of stent fractures are not well characterized. Care should also be taken when deploying the stent as excessive force could, in rare instances, lead to stent deformation and/or fracture.

Post Stent Placement Precautions

• Recrossing a deployed stent with adjunct devices must be performed with caution.
• In the event of thrombosis of the expanded stent, thrombolysis and PTA should be attempted.

Adverse Events (in alphabetical order) that may be associated with the use of the ENROUTE Transcarotid Stent System when used in conjunction with the ENROUTE Transcarotid NPS include, but may not be limited to (based upon clinical trial data for the PRECISE Stent System and the ANGIOGUARD XP Emboli Capture Guidewire and clinical trial data from the ROADSTER and PROOF studies):

• Air embolism
• Allergic/anaphylactoid reaction
• Anemia
• Aneurysm
• Angina/coronary ischemia
• Arrhythmia (including bradycardia, possibly requiring need for a temporary or permanent pacemaker)
• Arterial dissection
• Arterial occlusion/restenosis of the treated vessel
• Arterial occlusion/thrombus, at puncture site
• Arterial occlusion/thrombus, remote from puncture site
• Arteriovenous fistula
• Atelectasis
• Atrial fibrillation
• Bacteremia or septicemia
• Cerebral edema
• Congestive Heart Failure
• Death
• Embolization, arterial
• Embolization, stent
• Emergent repeat hospital intervention
• Fever
• Gastrointestinal disorders
• GI bleeding from anticoagulation/antiplatelet medication
• Hallucination
• Hematoma bleed, access site
• Hematoma bleed, remote site
• Hemorrhage
• Hyperperfusion syndrome
• Hypotension/hypertension
• Hypomagnesaemia
• Hypophoshatemia
• Infection
• Intimal injury/dissection
• Ischemia/infarction of tissue/organ
• Local infection and pain at insertion site
• Malposition (failure to deliver the stent to the intended site)
• Myocardial infarction
• Nausea 
• Oxygen saturation decrease
• Pain
• Pseudoaneurysm
• Rales
• Renal failure
• Respiratory infection
• Restenosis of the vessel (> 50% obstruction)
• Rhinorrhea
• Seizure
• Severe unilateral headache
• Stent migration
• Stent thrombosis
• Stroke
• Transient ischemic attacks
• Transient intolerance to reverse flow
• Urinary tract infection
• Vasospasm
• Venous occlusion/thrombosis, at puncture site
• Venous occlusion/thrombosis, remote from puncture site
• Vessel rupture, dissection, perforation
• Vomiting
• Wheezing

These access kits are intended to introduce up to a .038 inch guidewire or catheter into the peripheral vascular system, including the carotid artery, following a small gauge needle stick.

Use of the access kit is contraindicated if the patient has a known or suspected obstruction in the vessel. There is an increased risk of pneumothorax for the patient who has severe chronic lung disease. Poor healing may result in the patient who has had irradiation to the anterior chest.

• Do not alter this device in any way.
• Do not use alcohol, acetone or solutions containing these agents. These solutions may affect the properties of the plastic components resulting in degradation of the device.
• Do not reuse this device. Reuse will result in increased biocontamination risk for the patient resulting in infection or pyrogenic response.
• Do not withdraw guidewire through metal needles; guidewire may shear or unravel.
• Do not attempt to straighten a wire that has been kinked or bent.
• Do not advance a guidewire that is kinked or becomes kinked or bent.
• Do not rotate the guidewire if significant resistance is felt.
• Do not resterilize.

• Store in a dry, dark, cool place. Do not use if package is open or damaged. Inspect all components prior to use.
• USA CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician.

• The potential complications related to the use of the access kit include, but are not limited to the following: Air embolism, device embolism, device dislodgement, pneumothorax, vein thrombosis, hematoma formation, hemothorax, vessel erosion, trauma to vessels, sepsis

The ENROUTE Transcarotid 0.014” Guidewire is intended for use in the peripheral vasculature, inclusive of the carotid artery.

The ENROUTE Transcarotid 0.014” Guidewire is not intended for use in:

• The cerebral or coronary vasculature.
• Patients judged not acceptable for percutaneous intervention.

• A guidewire is a delicate instrument and must not be advanced, withdrawn, or torqued if resistance is met. Guidewire manipulations must always be observed under fluoroscopy
• If the guidewire is removed and is to be re-inserted, it must be gently wiped with saline soaked gauze or placed in a bowl of sterile saline and inspected for signs of damage (weakened or kinked segments) prior to re-introduction.
• Do not re-introduce if guidewire is weakened or kinked.
• If the wire is removed and not immediately reinserted, store the wire in a bowl of sterile saline in order to avoid particulate adhering to the activated hydrophilic coating of the guidewire.

Failure to follow the instructions may compromise guidewire performance and result in complications.

• Do not withdraw or manipulate the coated wire in a metal cannula or sharp-edged object.
• Avoid wiping the device with dry gauze as this may damage the device coating.
• Avoid using alcohol, antiseptic solutions or other solvents to pre-treat the guidewire as this may cause unpredictable changes in the coating which can affect the device safety and performance.
• Always inspect the guidewire carefully for bends, kinks or other damage prior to insertion or re-insertion. Do not use damaged guidewires.

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