NAVI-STAR DIAGNOSTIC/ABLATION DEFLECTABLE TIP CATHETER

{0} p990025 # SUMMARY OF SAFETY AND EFFECTIVENESS DATA P990025, Biosense Webster, Inc. NAVI-STAR® Diagnostic/Ablation Catheter ## TABLE OF CONTENTS 1. Summary of Safety and Effectiveness: 2 1.1 General Information 2 1.2 Indications for Use 2 1.3 Contraindications 3 1.4 Warnings and Precautions 3 1.5 Device Description 3 1.5.1 Procedure Components 3 1.6 Device Model Numbers 4 1.6.2 Compatible Radiofrequency Generators 6 1.7 Alternative Practices and Procedures 6 1.8 Marketing History 6 1.9 Adverse Effects of the Device on Health 6 1.9.1 Observed Adverse Events 6 1.9.2 Anticipated Adverse Events 8 1.10 Summary of Preclinical Studies 8 1.10.1 Bench Testing on Physical Properties of the NAVI-STAR® Catheter and REF-STAR® Catheter 8 1.10.2 NAVI-STAR® Catheter Upper Allowable Lesion Limit 12 1.10.3 Lesion Comparison Test for the NAVI-STAR® Catheter vs. the CELSIUS Catheter 13 1.10.4 Animal Testing 13 1.10.5 Biocompatibility Testing 13 1.11 Summary of Clinical Investigations 14 1.12 Conclusions Drawn from the Studies 18 1.13 Panel Recommendation 18 1.14 FDA Decision 18 1.15 Approval Specification 18 Page 1 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {1} # Summary of Safety and Effectiveness Data ## 1.1 GENERAL INFORMATION Device Generic Name: Diagnostic/Ablation Catheter Device Trade Name(s): NAVI-STAR® Diagnostic/Ablation Catheter Device Model Numbers: NAVI-STAR® Diagnostic/Ablation Catheter, D-1183/D-1184 *Catheter interface cables, D-1195 Applicant’s Name and Address: *As approved under P950005(Celsius) Biosense Webster, Inc. 3333 Diamond Canyon Road Diamond Bar, CA 91765 PMA Number: P990025 Date of Panel Recommendation: N/A Date of Notice of Approval to the Applicant: JUN 15 2000 ## 1.2 INDICATIONS FOR USE The NAVI-STAR® Diagnostic/Ablation Catheter, and related accessory devices are indicated for catheter-based atrial and ventricular cardiac mapping, and when used with a compatible radiofrequency generator in adults and children 4 years of age and older for: - interruption of accessory atrioventricular (AV) conduction pathways associated with tachycardia; including persistent junctional re-entrant tachycardia (PJRT) and Mahaim fibers; - the treatment of AV nodal re-entrant tachycardia; and - creation of complete AV nodal block in patients with a difficult to control ventricular response to an atrial arrhythmia. When used with the CARTO® EP Navigation System, the NAVI-STAR® Diagnostic/Ablation catheter provides location information. Page 2 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {2} # 1.3 CONTRAINDICATIONS Do not use this device; - in patients with active systemic infection; - via the transseptal approach in patients with left atrial thrombus or myxoma, or interatrial baffle or patch; - via the retrograde transaortic approach in patients with aortic valve replacement. # 1.4 WARNINGS AND PRECAUTIONS See Warnings and Precautions in the final approved labeling (Instructions for Use). # 1.5 DEVICE DESCRIPTION The NAVI-STAR® catheter and related accessory devices, is designed to acquire and analyze individual data points during mapping of the atrial and ventricular structures of the human heart. For ablation, the catheter is used in conjunction with a compatible RF generator and required accessories. # 1.5.1 Procedure Components The following commercially available devices are required to conduct an EP procedure: - grounding pad (dispersive pad); - electrocardiogram (ECG) leads; - electrophysiology (EP) recording equipment; - compatible radiofrequency (RF) generator; and - pacing stimulator. The above devices are sold separately, and are not covered by this PMA application. # 1.5.1.1 NAVI-STAR® Diagnostic/Ablation Catheter The NAVI-STAR® catheter is a steerable, multi-electrode catheter with a deflectable tip. The catheter provides information for electrophysiological mapping of the heart and transmits RF current through the catheter tip electrode for ablation purposes. When used with the CARTO® system and REF-STAR® reference device, a real-time 3D reconstruction of the heart chamber is provided. For ablation, the catheter is used in conjunction with a compatible RF generator and a commercially available dispersive pad. Page 3 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {3} The NAVI-STAR® catheter is a 7 F catheter with a usable length of $115 \pm 3 \mathrm{~cm}$; the device is provided sterile (EtO). The device has a high-torque polyurethane shaft with a deflectable tip section containing an array of platinum electrodes. All electrodes may be used for recording and stimulation, but only the tip electrode may be used to deliver RF energy from the generator. A magnetic location sensor embedded in the tip electrode transmits location information to the CARTO® system. The catheter is available with either a thermocouple or thermistor temperature sensor. Tip deflection is controlled at the proximal end by a tubular handpiece in which a piston slides; a thumb knob on the piston controls piston travel. The plane of the curved tip can be rotated and the shape of the curve depends on the deflectable tip length and the location of the puller-wire anchor in the deflectable tip. Seven curve types, designated "B" through "F," "J," and "L" are available as shown in Figure 1. The catheter interfaces with the CARTO® system and a compatible RF generator via an interface cable and a junction box.  Figure 1. Curve types for the NAVI-STAR® Diagnostic/Ablation Catheter. ## 1.6 DEVICE MODEL NUMBERS | Manufacturing Part No. | U.S. Catalog No. | Description | | --- | --- | --- | | D-1183 | NS7TC-BL-174-HS | NAVI-STAR® 7F catheter with thermocouple temperature sensor, 4 mm tip electrode, 1-7-4 mm spacing. Hypertronics connector, provided | | | NS7TC-CL-174-HS | | | | NS7TC-DL-174-HS | | | | NS7TC-EL-174-HS | | Page 4 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {4} | | NS7TC-FL-174-HS NS7TC-JL-174-HS NS7TC-LL-174-HS | sterile | | --- | --- | --- | | D-1184 | NS7T-BL-174-HS NS7T-CL-174-HS NS7T-DL-174-HS NS7T-EL-174-HS NS7T-FL-174-HS NS7T-JL-174-HS NS7T-LL-174-HS | NAVI-STAR® 7F catheter with thermistor temperature sensor, 4 mm tip electrode, 1-7-4 mm spacing, Hypertronics connector, provided sterile | | D-1195 | C5-MH/REFMH-S C5-MH/NAVMH-S C5-MH/XRFMH-S | NAVI-STAR® interface cables for use with the CARTO® system | The U.S. catalog numbers for the NAVI-STAR® catheters are “smart numbers” containing basic information regarding the device, as follows: NS7 = NAVI-STAR® 7 F device<br/> TC = Thermocouple temperature sensor<br/> T = Thermistor temperature sensor<br/> B,C,D,E,F,J,L = Available curve types<br/> L = Large dome (4mm tip electrode)<br/> 174 = Ring electrode spacing<br/> H = Hypertronics connector<br/> S = Sterile_product The smart numbers for the catheter interface cables contain the following information: C5 = 5 foot extension cable<br/> MH = Hypertronics connector<br/> REF = For use with REF-STAR® catheter<br/> NAV = For use with NAVI-STAR® catheter<br/> XRF = For use with REF-STAR® External Reference Patch<br/> S = Sterile_product ## 1.6.1.1 Catheter Interface Cables Biosense Webster manufactures a variety of interface cables for use with its diagnostic/ablation catheters and the CARTO® system. The catheter interface cables for use with the NAVI-STAR® catheter and REF-STAR® devices have locking connectors on both ends. The cables connect the NAVI-STAR® and REF-STAR® catheters to a junction box. Biosense Webster’s market-approved generator interface cables connect the junction box to a compatible RF generator. A description of these cables can be found in P950005. A description of the REF-STAR® and CARTO® system can be found in K000248. Page 5 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {5} Page 6 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter ## 1.6.2 Compatible Radiofrequency Generators The NAVI-STAR® catheter should be used only with a legally marketed, compatible RF generator which has been shown to be safe and effective for cardiac ablation. The following table lists specifications for compatible RF generators. ### SPECIFICATIONS FOR COMPATIBLE RF GENERATORS | Generator | Specification | | --- | --- | | Thermometry | Thermocouple or Thermistor | | Temperature Limit, Maximum | 100°C | | Modes: (must operate in all 3 modes) | Temperature Control Temperature Monitoring Power Control | | Maximum Output Power | 50 Watts | | RF Output Frequency | 450kHz – 550kHz | | Impedance Cut-off | High: 250Ω Low: 40Ω | ## 1.7 ALTERNATIVE PRACTICES AND PROCEDURES Alternative therapy for cardiac arrhythmia includes direct surgical ablation, use of drugs for tachycardia control, antitachycardia pacing, and RF ablation with various market-approved catheters. All of the alternative ablation catheters are placed and moved within the heart using fluoroscopy. ## 1.8 MARKETING HISTORY The NAVI-STAR® Diagnostic/Ablation Catheter has not been marketed in the United States. The NAVI-STAR® Diagnostic/Ablation Catheter is available for sale in Canada, Europe, and South America. There are no countries from which the NAVI-STAR® catheter, or the related accessory devices, have been withdrawn from marketing for any reason related to safety or effectiveness. ## 1.9 ADVERSE EFFECTS OF THE DEVICE ON HEALTH ### 1.9.1 Observed Adverse Events The Biosense Webster NAVI-STAR® Diagnostic/Ablation Catheter was studied in 320 enrolled patients undergoing electrophysiologic (EP) mapping and RF catheter ablation to eliminate atrioventricular (AV) accessory pathways (AP) associated with tachycardia due to Wolff-Parkinson-White (WPW) syndrome. AV nodal re-entrant tachycardia {6} (AVNRT), or creation of complete AV nodal (AVN) block in patients with difficult to control ventricular response to an atrial arrhythmia. Three hundred twenty (320) patients were enrolled in the clinical study. Two hundred eighty-one (281) enrolled patients underwent RF ablation. These patients were followed for a mean of 8.22 months with a standard deviation of 4.37. The maximum length of follow-up was 20.39 months. All 281 patients undergoing RF ablation were included in the safety database. Sixteen adverse events were reported for the 281 patients who received ablation therapy; seven of these events were classified as major adverse events. Major and minor adverse events were classified according to the FDA's recommended definitions for evaluating ablation safety. The major adverse events, occurring within seven days post ablation, included complete heart block that required placement of a permanent pacemaker (2 patients); atrial puncture caused by a transseptal sheath (1 patient); retroperitoneal hemorrhage resulting from a groin stick for venous access (1 patient); minor (non-q-wave) myocardial infarction (1 patient), cardiac tamponade (1 patient), and pulmonary edema (1 patient). Minor adverse events included tricuspid regurgitation (2 patients); transient heart block (1 patient); pericardial effusion (1 patient) and dehydration (1 patient), dermal hypersensitivity (1 patient), femoral pseudoaneurysm (1 patient), mild fever with myalgia (1 patient), and trace pericardial effusion (1 patient). Three deaths were reported for the study (the patients expired 12 days, 34 days, and 49 days, respectively, post-procedure). All deaths were due to complications associated with the patient's primary disease condition. A summary of observed adverse events for all ablated patients is provided in the following table: Observed Adverse Events/Deaths (N=281) | Adverse Event Classification | % patients | Number of patients | 95% Confidence Interval* | | | --- | --- | --- | --- | --- | | Major | 2.5% | 7/281 | 0.010 | 0.053 | | Minor | 3.2% | 9/281 | 0.015 | 0.061 | | Death | 1.1% | 3/281 | 0.002 | 0.034 | *Confidence intervals by exact (binomial) method Page 7 - Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {7} Page 8 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter ## 1.9.2 Anticipated Adverse Events Adverse events (in alphabetical order) which may be associated with catheterization and ablation include: - Air embolism - Arrhythmias - AV fistula - Cardiac perforation/tamponade - Cardiac thromboembolism - Cerebrovascular accident (CVA) - Chest pain/discomfort - Complete heart block - Coronary artery dissection - Coronary artery spasm - Coronary artery thrombosis - Hemothorax - Increased phosphokinase level. - Laceration - Local hematomas/ecchymosis - Myocardial Infarction - Pericardial effusion - Pericarditis - Pleural effusion - Pneumothorax - Pseudoaneurysm - Pulmonary edema - Pulmonary embolism/tamponade - Thrombi - Thromboembolism - Thrombosis - Transient ischemic attack (TIA) - Valvular damage - Vascular bleeding/local hematomas - Vasovagal reactions - Ventricular tachyarrhythmia ## 1.10 SUMMARY OF PRECLINICAL STUDIES Nonclinical bench testing and animal testing have been conducted to demonstrate the safety and reliability and performance specifications of the NAVI-STAR® Catheter. The following sections summarize the results of this testing. ### 1.10.1 Bench Testing on Physical Properties of the NAVI-STAR® Catheter and REF-STAR® Catheter Design verification testing of the NAVI-STAR® catheter was conducted to establish conformance with applicable standards and FDA guidance documents. (For the purpose of this test, the NAVI-STAR® catheter was chosen as the worst-case example for the NAVI-STAR® family of devices.) Using standard methods consistent with the ANSI standard for Electrosurgical Devices (HF-18), AAMI standards for ECG connectors (ECGC), and the agency’s “Electrode Recording Catheter Preliminary Guidance” (1995) and the “Cardiac Ablation Preliminary Guidance” (1995), the catheter design was evaluated to demonstrate structural integrity and design performance. The integrity of the shaft, tip electrode, sensor housing, location sensor, and temperature sensors were tested on the bench, and under simulated use conditions. Reliability testing was conducted on sterilized catheters. The catheters were {8} evaluated for fatigue resistance, joint integrity, torsion, and tensile strength. All test samples met the established acceptance criteria for reliability testing. ## RELIABILITY TESTING | Test | Number | Acceptance Criteria | Results | | --- | --- | --- | --- | | Deflection | 20 | No mechanical failures before 200 cycles | All samples passed | | Flex cycles | 20 | No mechanical failures before 10 cycles | All samples passed | | Gas pressure/joint seal | 20 | Minimum pressure 4.6 psi | All samples passed | | Torque Barrel to Connector | 10 | Withstands ≥ 9 oz-in | All samples passed | | Torque Entire Catheter | 5 | Withstands > 2 turns | All samples passed | | Torque Tip Electrode to Soft Tip Joint | 5 | Withstands ≥ 2.6 oz-in | All samples passed | | Torque Shaft to Tip Joint | 5 | Withstands > 2 turns | All samples passed | | Torque Plot* | 20 | Withstands > 2 turns | All samples passed | | Torque Shaft to Piston Joint | 5 | Withstands > 2 turns | All samples passed | | Pull Test Barrel to Connector | 10 | Withstands ≥ 15 lbs | All samples passed | | Pull Test Entire Catheter | 5 | Withstands ≥ 4 lbs | All samples passed | | Pull Test Tip Electrode to Soft Tip Joint | 5 | Withstands ≥ 4 lbs | All samples passed | | Pull Test Shaft to Tip Joint | 5 | Withstands ≥ 4 lbs | All samples passed | | Pull Test Shaft to Piston Joint | 5 | Withstands ≥ 4 lbs | All samples passed | Mechanical performance testing was conducted on sterilized catheters. All test samples met the established acceptance criteria for mechanical testing. ## MECHANICAL PERFORMANCE TESTING | Test | Number of Devices Tested | Acceptance Criteria | Results | | --- | --- | --- | --- | | Soak | 20 | No mechanical failures after 5 hour soak in 37°C saline bath | All samples passed | | Steering Through Vascular Model | 20 | No mechanical failures before 20 insertions | All samples passed | | Steering | 20 | No mechanical failures before 100 cycles | All samples passed | | Bending Test | 20 | Baseline testing of catheter deflection with masses of: 50 g 100 g 150 g | All samples passed (characterization test: no set acceptance | Page 9 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {9} # MECHANICAL PERFORMANCE TESTING | Test | Number of Devices Tested | Acceptance Criteria | Results | | --- | --- | --- | --- | | | | 200 g | criteria) | | Tip Stiffness | 20 | Stiffness <27 g | All samples passed | | Side Force | 20 | Withstands >4 g | All samples passed | | Buckle Test | 20 | Baseline testing | All samples passed | Electrical performance testing was conducted on sterilized catheters five times during the qualification test (pre- and post-simulated ablation) to ensure that electrical performance was not compromised during the test cycle. All test samples met the established acceptance criteria for electrical performance testing. # ELECTRICAL PERFORMANCE TESTING | Test | Number of Devices Tested | Acceptance Criteria | Results | | --- | --- | --- | --- | | DC Lead Resistance | | | | | Pre-simulated ablation #1 | 20 | <10 Ω and within 0.4 Ω of each other | All samples passed | | Pre-simulated ablation #2 | 20 | | | | Pre-simulated ablation #3 | 20 | | | | Post-simulated ablation #1 | 20 | | | | Post-simulated ablation #2 | 20 | | | | DC Isolation Resistance | | Measured resistance >200 kΩ | All samples passed | | Pre-simulated ablation #1 | 20 | | | | Pre-simulated ablation #2 | 20 | | | | Pre-simulated ablation #3 | 20 | | | | Post-simulated ablation #1 | 20 | | | | Post-simulated ablation #2 | 20 | | | Page 10 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {10} # ELECTRICAL PERFORMANCE TESTING | Test | Number of Devices Tested | Acceptance Criteria | Results | | --- | --- | --- | --- | | RF Lead Impedance @ 5 kHz | | | | | Pre-simulated ablation | 20 | Impedance <10 Ω | All samples passed | | Post-simulated ablation | 20 | | | | RF Lead Impedance @ 500 kHz | | | | | Pre-simulated ablation | | Impedance <25 Ω | All samples passed | | Post-simulated ablation | 20 | | | | | 20 | | | | RF Isolation Impedance @ 5 kHz | | | | | Pre-simulated ablation | | Impedance @ 5 kHz | | | Post-simulated ablation | 20 | >100 kΩ | All samples passed | | | 20 | Phase angle between -86° to -90° | | | RF Isolation Impedance @ 500 kHz | | | | | Pre-simulated ablation | | Impedance @ 500 kHz | All samples passed | | Post-simulated ablation | 20 | >1 kΩ | | | | 20 | Phase angle between -86° to -90° | | | Temperature Reading | | | | | Thermocouple Sensor | | | | | Pre-simulated ablation | 10 | Thermocouple thermometer reading 60 ± 2°C | All samples passed | | Post-simulated ablation | 10 | | | | Thermistor Sensor | | | | | Pre-simulated ablation | 10 | Thermistor resistance reading 5.80 kΩ - 6.92 kΩ at 60°C | All samples passed | | Post-simulated ablation | 10 | | | | Verify PCB Calibration | 20 | Calibration results read “OK” | All samples passed | | Leakage Current | 20 | Measured RF leakage current ≤ 290 mA | All samples passed | Page 11 – Summary of Safety and Effectiveness Data for P990025. BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {11} Simulated use ablation was conducted to evaluate the functional performance of the catheter, cables, and CARTO® system. Lesion volume was measured for 10 of the 20 catheters, and was found to be comparable for all lesions and catheters. ## FUNCTIONAL PERFORMANCE TESTING | Name of Test | Number of Devices Tested | Acceptance Criteria | Results | | --- | --- | --- | --- | | Visual Inspection Post-Ablation | 20 | No mechanical failures | 19/20 samples passed* | | Lesion Volume | 10 | Consistent lesions should be created for 10 catheters | Consistent lesions were produced | * One sample failed due to a break in the tip electrode leadwire. ## In Vitro Location Accuracy: **Location Accuracy:** Location accuracy of the CARTO® system, and ablation characteristics of the NAVI-STAR® catheter when used with the CARTO® system were assessed *in vitro* and *in vivo*. The studies found that the CARTO® system is accurate in locating the NAVI-STAR® catheter on the bench, in animals, and in humans. Location accuracy is the difference between the actual catheter position and the CARTO® reported position. Two *in vitro* studies were conducted to evaluate the location accuracy of the CARTO® system. These studies support the claim that the CARTO® system has a location accuracy of &lt;1mm in a static environment. Beat-to-beat system variation, when measured in a dynamic animal model, was found to have an average maximal range and average mean error of 1.26±0.08 mm and 0.54±0.05 mm, respectively. ## 1.10.2 NAVI-STAR® Catheter Upper Allowable Lesion Limit A study was conducted to evaluate an upper limit for the number of lesions that can be created using a single NAVI-STAR® catheter. All catheters were subjected to electrical testing pre- and post-ablation, with satisfactory results. Reliability testing was performed post-ablation, and all catheters met the acceptance criteria. Based on this test it was concluded the NAVI-STAR® catheter is capable of delivering RF current for 250 minutes without degradation in physical characteristics or functional performance. Page 12 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {12} # 1.10.3 Lesion Comparison Test for the NAVI-STAR® Catheter vs. the CELSIUS Catheter A study was conducted to compare the lesions created with NAVI-STAR® catheters to lesions created with CELSIUS catheters. The CELSIUS catheter is a market approved catheter for the same indications for use as the NAVI-STAR®; that was approved under P950005. The results demonstrated no statistically significant difference in the volume of the lesions created by the NAVI-STAR® catheter when compared to lesions created by Celsius catheter. # 1.10.4 Animal Testing Animal studies were conducted to evaluate mapping accuracy and lesion characteristics and reproducibility of the CARTO® system and NAVI-STAR® catheter. - Beat-to-beat system variation, when measured in a dynamic animal model, was found to have an average maximal range and average mean error of $1.26 \pm 0.08 \mathrm{~mm}$ and $0.54 \pm 0.05 \mathrm{~mm}$, respectively. - The NAVI-STAR® catheter, when used with the CARTO® system, produces a reconstruction map that is consistent with the known anatomy and electrical activity of the pig heart. - Studies performed in the swine RA show that the NAVI-STAR® catheter produces reconstruction of the atrium that allows accurate guidance for catheter ablation procedures: the location, shape, and continuity of the linear lesions corresponded to the autopsy findings. The studies found that the NAVI-STAR® catheter, when used in conjunction with the CARTO® system and related accessory devices, can safely, consistently, and reliably map and ablate in the swine heart. # 1.10.5 Biocompatibility Testing The patient-contacting materials of the NAVI-STAR® catheter were tested according to ISO 10993-1:1 and ISO 10993-4. Under the ISO guidance, electrode catheters are classified as limited (&lt;24 hour) contact duration, circulating blood, externally communicating devices. The test data established the biocompatibility of the catheter materials for the intended use. Page 13 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {13} Page 14 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR™ Diagnostic/Ablation catheter # RESULTS OF CATHETER BIOCOMPATIBILITY TESTING | Test | Results | | --- | --- | | Cytotoxicity Test Using the ISO Elution Method in the L-929 Mouse Fibroblast Cell Line | Passed. The MEM test extracts showed no evidence of causing cell lysis or toxicity. The negative controls, reagent controls, and the positive controls performed as anticipated. Under the conditions of this study, the MEM test extracts were not cytotoxic. | | Delayed Contact Sensitization Study (A Maximization Method) in the Guinea Pig (Saline and Cottonseed Oil Extracts) | Passed. Under the conditions of this study, the extracts showed no evidence of causing delayed contact sensitization in the guinea pig. | | Acute Intracutaneous Reactivity Study in the Rabbit (Saline and Cottonseed Oil Extracts) | Passed. There was no evidence of significant irritation or toxicity from the extracts injected intracutaneously into rabbits. The Primary Irritation Index for the extracts was negligible. | | USP Systemic Toxicity Study in the Mouse (Saline and Cottonseed Oil Extracts) | Passed. There was no mortality or evidence of significant toxicity from the extracts. Each test article extract met the USP requirements. | | Thromboresistance in Two Dogs (in vivo) | Passed. Under the conditions of this study, the test article exhibited minimal to no thrombus, while the control article resisted thrombogenicity. | | Hemocompatibility Hemolysis in vitro procedure (Extraction) | Passed. Under the conditions of this study, the mean hemolytic index for the test article extract was 0%. The test article extract was considered to be nonhemolytic. | | Rabbit Pyrogen Study – Material Mediated | Passed. The total rise of rabbit temperatures during the 3-hour observation period was within acceptable USP limits. The test extract was judged as nonpyrogenic. | | Complement Activation Assay – ISO | Passed. The human plasma exposed to the test article did not exhibit increased C3a or SC5b-9 as compared to both untreated plasma and negative control plasma. The test article did not induce complement activation of C3 or C5 proteins in human plasma. | ## 1.11 SUMMARY OF CLINICAL INVESTIGATIONS The NAVI-STAR® Diagnostic/Ablation Catheter, when used in conjunction with the CARTO system and related accessory devices was evaluated in a clinical study with the Medtronic CardioRhythm Atakr RF generator, and the EPT RF generator for the treatment of supraventricular tachycardias. {14} Study Design: The NAVI-STAR® Diagnostic/Ablation Catheter was evaluated in a prospective, non-randomized, multi-center study. Acute success was defined as the inability to induce the arrhythmia for WPW and AVNRT patients, and complete heart block for AVN patients, following the ablation procedure. Chronic (3 month) success was defined as the absence of recurrence of the arrhythmia over a 3 month monitoring period. Patients Studied: Of the 320 patients enrolled, 281 patients underwent ablation and provided clinical data for the assessment of safety. For the effectiveness endpoints, the patient count included all patients treated with the NAVI-STAR® Diagnostic/Ablation Catheter, including those patients where the physician began the procedure using the NAVI-STAR® Diagnostic/Ablation Catheter and then changed to a non-protocol device to complete the procedure. The patients who began treatment with the NAVI-STAR® Diagnostic/Ablation Catheter, but were switched to a non-protocol device were considered treatment failures. Therefore, two hundred seventy-seven (277) patients were treated with the NAVI-STAR® Diagnostic/Ablation Catheter for an arrhythmia indicated in the study and were assessed for effectiveness. The other 39 patients were discontinued prior to ablation for the reasons and occurrence indicated in the table below: Patients Discontinued Prior to Ablation | Reason for Discontinuation | Number of Patients | | --- | --- | | Physician chose not to ablate (difficult pathway, close proximity to AV node, unusual location, or other) | 3 | | Unable to induce protocol arrhythmia | 22 | | Non-protocol arrhythmia | 14 | | Total number of discontinued patients: | 39 | Demographics: Of the 281 patients undergoing RF ablation, 158 (56%) were female and 123 (44%) were male, which is consistent with the prevalence of the disease. The mean age for all patients was 49 years (range 10-86). The distribution of supraventricular tachycardias treated is shown in the following table. Page 15 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {15} Distribution of Arrhythmias Treated | Indication | Number of patients | | | --- | --- | --- | | | % | # | | WPW | 24% | 69/281 | | AVNRT | 56% | 156/281 | | WPW/AVNRT | 1% | 4/281 | | AVNRT/other arrhythmia | 2% | 7/281 | | AV Node Ablation | 14% | 41/281 | | Non-study arrhythmia | % | 4/281 | | All Patients | 100% | 281 | Intraprocedural Data: For the 281 patients ablated, RF current was applied a total of 2,289 times during the study with a mean of 8.4 applications per patient (range 1-58) and a mean duration of 40.9 seconds per application (range 1-328). The mean temperature per application was 56.8°C (range 35-100°C). Mean fluoroscopy time was 20.4 minutes, and mean total procedure time was 194.5 minutes. Acute Effectiveness: Of the 277 patients treated with the NAVI-STAR® Diagnostic/Ablation Catheter, acute success was achieved in 269 patients (97.1%). The table below summarizes acute success rates by indication and group. Acute Procedural Success by Indication (n=277) | Indication | % | # | 95% Confidence Interval | | --- | --- | --- | --- | | WPW | 95.7% | 66/69 | [0.878, 0.991] | | AVNRT | 97.5% | 159/163 | [0.938, 0.993] | | WPW/AVNRT | 100% | 4/4 | [0.398, 1] | | AVNRT/supplemental arrhythmia* | 100% | 4/4* | [0.398, 1] | | AV Node Ablation | 97.6% | 40/41 | [0.871, 0.999] | | All Patients | 97.1% | 269/277 | [0.944, 0.987] | * Not counted in total Chronic Effectiveness: Of the 198 patients available for 3-month follow-up, chronic success was achieved in 185 (93.4%). Six-month chronic success was reported for 159 Page 16 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {16} (95.7%) of 166 core patients available for follow-up. The tables below summarize chronic success rates by indication and group. 95% confidence interval Chronic Success by Indication at 3 Months | Indication | 3 Months | | 95% Confidence Interval | | | --- | --- | --- | --- | --- | | | % | # | Lower Limit | Upper Limit | | WPW | 95.3% | 41/43 | 0.842 | 0.994 | | AVNRT | 93.0% | 107/116 | 0.858 | 0.964 | | WPW/AVNRT | 100% | 4/4 | 0.398 | 1.000 | | AVNRT/other arrhythmia | 100% | 5/5 | 0.478 | 1.000 | | AV Node Ablation | 93.1% | 27/29 | 0.772 | 0.992 | | AV Node Ablation & Other | 100% | 1/1 | 0.025 | 1.000 | | All Patients | 93.4% | 185/198 | 0.890 | 0.965 | 95% confidence interval Chronic Success by Indication at 6 Months | Indication | 6 Months | | 95% Confidence Interval | | | --- | --- | --- | --- | --- | | | % | # | Lower Limit | Upper Limit | | WPW | 91.2% | 31/34 | 0.763 | 0.981 | | AVNRT | 94.7% | 89/94 | 0.880 | 0.983 | | WPW/AVNRT | 100% | 3/3 | 0.292 | 1.000 | | AVNRT/other arrhythmia | 100% | 2/2 | 0.158 | 1.000 | | AV Node Ablation | 100% | 25/25 | 0.863 | 1.000 | | AV Node Ablation & Other | 100% | 1/1 | 0.025 | 1.000 | | All Patients | 95.0% | 151/159 | 0.903 | 0.978 | In separate clinical studies for a PMA approved ablation catheter (CELSIUS® P95005), Biosense Webster collected the clinical data shown in the table below. Page 17 – Summary of Safety and Effectiveness Data for P990025. BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter {17} Device Performance Compared to Control Group | Study Endpoint | NAVI-STAR® Catheter | Control | Exact One-Sided 95% Confidence Bound | | --- | --- | --- | --- | | Acute Success | 97.1% | 92.1% | 93.9% | | Chronic Success | 93.4% | 91.5% | 88.4% | | Major Complications | 1.8% | 3.5% | 4.4% | The safety, acute effectiveness, and chronic effectiveness results from the NAVI-STAR® Diagnostic/Ablation Catheter study were demonstrated to be statistically equivalent to the control data. ## 1.12 CONCLUSIONS DRAWN FROM THE STUDIES Preclinical testing demonstrates that the NAVI-STAR® Diagnostic/Ablation catheter should maintain its mechanical and electrical integrity, and that the patient contacting materials should be biocompatible under the proposed conditions of use. The bench testing established an appropriate degree of localization accuracy. Clinical data submitted under P990025 provide reasonable assurance that the NAVI-STAR® Diagnostic/Ablation catheter is reasonably safe and effective for the stated indications under the proposed conditions of use. ## 1.13 PANEL RECOMMENDATION Pursuant to the provision of Section 515 (c) (2) of the Food Drug and Cosmetic Act (FD&amp;C) as amended by the Safe Medical Devices Act of 1990 (SMDA 1990), this PMA application was not referred to the Circulatory System Devices Panel, and FDA Advisory Panel Committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this Panel. ## 1.14 FDA DECISION FDA determined that the device is reasonably safe and effective when used as indicated in the labeling. CDRH issued an approval order for the applicant’s PMA, P990025, on —JUN—15 2000 ## 1.15 APPROVAL SPECIFICATION - Directions for Use: See final approved labeling (Instructions for Use) - Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings and Precautions, and Adverse Events in the final approved labeling (Instructions for Use) - Post-Approval Requirements and Restrictions: See Approval Order. Page 18 – Summary of Safety and Effectiveness Data for P990025, BioSense Webster, Inc., NAVI-STAR® Diagnostic/Ablation catheter