← Product Code MLV · P000039 # THE AMPLATZER(R) SEPTAL OCCLUDER (ASO) AND THE AMPLATZER EXCHANGE SYSTEM (P000039) _ABBOTT MEDICAL · MLV · Dec 5, 2001 · Cardiovascular · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P000039 ## Device Facts - **Applicant:** ABBOTT MEDICAL - **Product Code:** MLV - **Decision Date:** Dec 5, 2001 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Cardiovascular - **Attributes:** Therapeutic ## Intended Use The AMPLATZER® Septal Occluder (ASO) device is indicated for the occlusion of atrial septal defects (ASD) in secundum position. The ASO device is also indicated in patients who have undergone a fenestrated Fontan procedure and who now require closure of the fenestration. Patients indicated for ASD closure have echocardiographic evidence of ostium secundum atrial septal defect and clinical evidence of right ventricular volume overload (i.e., 1.5:1 degree of left to right shunt or RV enlargement). ## Device Story The AMPLATZER Septal Occluder is a self-expandable, double-disc device composed of Nitinol wire mesh filled with polyester fabric. It is delivered via a transcatheter approach using a specialized delivery system (sheath, dilator, loading device, and delivery cable). The device is deployed under echocardiographic guidance to occlude atrial septal defects or fenestrated Fontan communications. The discs anchor the device across the defect, promoting endothelialization and permanent closure. The procedure is performed by interventional cardiologists in a clinical setting. By providing a minimally invasive alternative to open-heart surgery, the device reduces hospital stay duration and avoids the risks associated with cardiopulmonary bypass. Clinical success is monitored via echocardiography to confirm defect closure and assess for residual shunts. ## Clinical Evidence Pivotal multi-center, non-randomized study of 442 patients (423 treated) compared to 154 surgical controls. Primary endpoints: technical success, procedure success, and 12-month composite success. 12-month closure success was 98.5% for the device vs 100% for surgery. Major adverse event rate was 1.6% for the device vs 5.2% for surgery (p=0.030). Registry study of 48 Fenestrated Fontan patients showed 100% 12-month success. Bench testing confirmed structural integrity (400 million cycles) and MRI safety up to 1.5 Tesla. ## Technological Characteristics Self-expandable double-disc occluder; materials: Nitinol wire mesh (nickel-titanium alloy) and polyester fabric. Dimensions: 4mm to 38mm sizes. Delivery system includes sheath, dilator, loading device, and delivery cable. Sterilization: Ethylene oxide (SAL 10^-6). Biocompatibility per ISO 10993. MRI safe up to 1.5 Tesla. Corrosion testing per ASTM F746. ## Regulatory Identification Approved PMA: P000039 ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} SSED P000039 The AMPLATZER® Septal Occluder System Summary of Safety and Effectiveness Data Table of Contents 1. General Information... 1 2. Indications And Usage ... 1 3. Contraindications ... 2 4. Warnings and Precautions ... 2 5. Device Description ... 2 6. Alternative Practices or Procedures ... 4 7. Marketing History ... 5 8. Adverse Events ... 6 8.1 Adverse Events of the Device on Health ... 6 8.2 Potential Adverse Events ... 7 9. Summary Of Preclinical Studies ... 8 9.1 Bench Testing ... 8 9.2 MRI Compatibility ... 10 9.3 Corrosion Testing ... 10 9.3.1 Corrosion – Bench Testing ... 10 9.3.2 Corrosion – Animal Testing ... 11 9.3.3 Abrasion ... 11 9.4 Biocompatibility Tests ... 11 9.5 Useful Life (Sterilization/Shelf Life) ... 12 9.6 Animal Testing ... 12 10. Summary Of Clinical Studies ... 13 10.1 Objective ... 13 10.2 Study Design ... 13 10.3 Patient Description and Accountability ... 14 11. Data Analysis and Results ... 15 12. Device Failures and Replacements ... 17 13. Conclusions Drawn From The Studies ... 17 13.1 Atrial Septal Defects ... 17 13.2 Fenestrated Fontan ... 18 14. Panel Recommendation ... Error! Bookmark not defined. 15. CDRH Decision ... Error! Bookmark not defined. 16. Approval Specifications ... Error! Bookmark not defined. {1} SSED Page 1 P000039 # 1. General Information Device Generic Name: Transcatheter Atrial Septal Defect Occlusion Device Device Trade Name: AMPLATZER® Septal Occluder and AMPLATZER® Delivery System Applicant's Name and Address: AGA Medical Corporation 682 Mendelssohn Avenue Golden Valley, MN 55427 USA Date(s) of Panel Recommendation: September 10, 2001 Premarket Approval Application (PMA) Number: P000039 Date of Good Manufacturing Practice Inspection: October 2000 Date of Notice of Approval to Applicant: # 2. Indications And Usage The AMPLATZER® Septal Occluder (ASO) device is indicated for the occlusion of atrial septal defects (ASD) in secundum position. The ASO device is also indicated in patients who have undergone a fenestrated Fontan procedure and who now require closure of the fenestration. Patients indicated for ASD closure have echocardiographic evidence of ostium secundum atrial septal defect and clinical evidence of right ventricular volume overload (i.e., 1.5:1 degree of left to right shunt or RV enlargement). {2} # 3. Contraindications 3.1 Any patient known to have extensive congenital cardiac anomaly which can only be adequately repaired by way of cardiac surgery. 3.2 Any patient known to have sepsis within one month prior to implantation, or any systemic infection that cannot be successfully treated prior to device placement. 3.3 Any patient known to have a bleeding disorder, untreated ulcer or any other contraindications to aspirin therapy, unless another anti-platelet agent can be administered for 6 months. 3.4 Any patient known to have a demonstrated intracardiac thrombi on echocardiography (especially left atrial or left atrial appendage thrombi). 3.5 Any patient whose size (i.e., too small for TEE probe, catheter size, etc) or condition (active infection, etc) would cause the patient to be a poor candidate for cardiac catheterization. 3.6 Any patient with the margins of the defect <5mm to the coronary sinus, AV valves or right upper lobe pulmonary vein. # 4. Warnings and Precautions The warnings and precautions can be found in the AMPLATZER Septal Occluder final labeling (Instructions for Use). # 5. Device Description The AMPLATZER® Septal Occluder is a self-expandable, double disc device made from a Nitinol wire mesh. The two discs are linked together by a short connecting waist corresponding to the size of the ASD. In order to increase its closing ability, the discs and the waist are filled with polyester fabric. The polyester fabric is securely sewn to each disc by a polyester thread. SSED P000039 {3} SSED Page 3 P000039 # Device Specifications ![img-0.jpeg](img-0.jpeg) Table 1 - Device Specifications / Recommended sheath sizes | Order Number | A DEVICE SIZE (=STRETCHED ASD) | B LA DISC DIAMETER | WIDTH OF CONNECTING WAIST | C RA DISC DIAMETER | SMALLEST RECOMMENDED SHEATH SIZE | | --- | --- | --- | --- | --- | --- | | 9-ASD-004 | 4 mm | 16 mm | 3 mm | 12 mm | 6-7 French | | 9-ASD-005 | 5 mm | 17 mm | 3 mm | 13 mm | 6-7 French | | 9-ASD-006 | 6 mm | 18 mm | 3 mm | 14 mm | 6-7 French | | 9-ASD-007 | 7 mm | 19 mm | 3 mm | 15 mm | 6-7 French | | 9-ASD-008 | 8 mm | 20 mm | 3 mm | 16 mm | 6-7 French | | 9-ASD-009 | 9 mm | 21 mm | 3 mm | 17 mm | 6-7 French | | 9-ASD-010 | 10 mm | 22 mm | 3 mm | 18 mm | 6-7 French | | 9-ASD-011 | 11 mm | 25 mm | 4 mm | 21 mm | 7 French | | 9-ASD-012 | 12 mm | 26 mm | 4 mm | 22 mm | 7 French | | 9-ASD-013 | 13 mm | 27 mm | 4 mm | 23 mm | 7 French | | 9-ASD-014 | 14 mm | 28 mm | 4 mm | 24 mm | 7 French | | 9-ASD-015 | 15 mm | 29 mm | 4 mm | 25 mm | 7 French | | 9-ASD-016 | 16 mm | 30 mm | 4 mm | 26 mm | 7 French | | 9-ASD-017 | 17 mm | 31 mm | 4 mm | 27 mm | 7 French | | 9-ASD-018 | 18 mm | 32 mm | 4 mm | 28 mm | 8-9 French | | 9-ASD-019 | 19 mm | 33 mm | 4 mm | 29 mm | 8-9 French | | 9-ASD-020 | 20 mm | 34 mm | 4 mm | 30 mm | 8-9 French | | 9-ASD-022 | 22 mm | 36 mm | 4 mm | 32 mm | 9 French | | 9-ASD-024 | 24 mm | 38 mm | 4 mm | 34 mm | 9 French | | 9-ASD-026 | 26 mm | 40 mm | 4 mm | 36 mm | 10 French | | 9-ASD-028 | 28 mm | 42 mm | 4 mm | 38 mm | 10 French | | 9-ASD-030 | 30 mm | 44 mm | 4 mm | 40 mm | 10 French | | 9-ASD-032 | 32 mm | 46 mm | 4 mm | 42 mm | 10 French | | 9-ASD-034 | 34 mm | 50 mm | 4 mm | 44 mm | 12 French | | 9-ASD-036 | 36 mm | 52 mm | 4 mm | 46 mm | 12 French | | 9-ASD-038 | 38 mm | 54 mm | 4 mm | 48 mm | 12 French | The AMPLATZER® Delivery System includes: - Delivery Sheath with Touhy-Borst Adapter - used to deliver the device. - Dilator – used to ease penetration of tissue. - Loading Device – used to introduce the AMPLATZER Septal Occluder into the delivery sheath. - Plastic Vise – facilitates directional control and serves as the “handle” for disconnecting (unscrewing) the delivery cable from the device. - Delivery Cable – the device is screwed onto the distal tip of the delivery cable, which allows for placement (and if necessary, retrieval) of the device. {4} ![img-1.jpeg](img-1.jpeg) Figure 1 AMPLATZER Septal Occluder Device and Delivery System ## 6. Alternative Practices or Procedures The only alternative to device closure of an ASD is open-heart surgery. Cardiac surgery that is required for closure of such defects is a major procedure that requires cardiopulmonary bypass. Surgery is relatively safe with a mortality of less than 1%. If the patient suffers from coexistent medical illnesses such as pulmonary disease, diabetes, renal failure, etc., the risks of surgery are higher. SSED P000039 {5} SSED Page 5 P000039 # 7. Marketing History These devices have not been marketed in the United States. The AMPLATZER Septal Occluder and Delivery System received the CE Mark in 1998. Additionally the AMPLATZER Septal Occluder and Delivery System has been marketed in the following countries: | Africa | India | Saudi Arabia | | --- | --- | --- | | Argentina | Israel | Singapore | | Australia | Italy | Slovakia | | Austria | Jordan | Spain | | Belgium | Korea | Sweden | | Brazil | Kuwait | Switzerland | | Canada | Lebanon | Taiwan | | Chile | Malaysia | Thailand | | China | Mexico | The Netherlands | | Colombia | Monaco | Tunisia | | Costa Rica | New Zealand | Turkey | | Czech Republic | Norway | United Kingdom | | Denmark | Pakistan | Uruguay | | Finland | Poland | Venezuela | | France | Portugal | | | Germany | Russia | | | Greece | | | | Hong Kong | | | {6} The AMPLATZER Septal Occluder has not been withdrawn from marketing for any reason relating to the safety and effectiveness of the device. The AMPLATZER Delivery Systems were voluntarily recalled by AGA Medical due to reports of dislodgment and embolization of the delivery sheath distal tip marker band. The sheaths are no longer manufactured with marker bands. ## 8. Adverse Events ### 8.1 Adverse Events of the Device on Health The AMPLATZER Septal Occluder was evaluated in a multi-center, non-randomized, pivotal study comparing the device to surgical closure of atrial septal defects; 423 patients received 433 devices with a total device exposure of 911.5 years. Individual patient exposure to the device averaged 25.6 months (ranging from 0 to 38.9). A Registry group was also studied to evaluate the device in patients with other conditions appropriate for device closure. Forty-eight (48) patients with Fenestrated Fontan (FF) (communication in the baffle with at least 5mm distance from the free atrial wall and central venous pressure less than 15Hg) were enrolled in the study. There was one death reported in the pivotal study (device group) and no deaths were reported in the Fenestrated Fontan Registry Group. The Data Safety Monitoring Board determined that the death was not device or procedure related. Table 1 Adverse Events – Pivotal Study | Major Adverse Events | AMPLATZER Patients | Surgical Control Patients | p-value | | --- | --- | --- | --- | | Cardiac Arrhythmia requiring major treatment | 2/442 (0.5%) | 0/154 (0.0%) | 1.00 | | Device Embolization with surgical removal | 3/442 (0.7%) | 0/154 (0.0%) | 0.57 | | Device Embolization with percutaneous removal | 1/442 (0.2%) | 0/154 (0.0%) | 1.00 | | Delivery System Failure | 1/442 (0.2%) | 0/154 (0.0%) | 1.00 | | Pericardial Effusion with tamponade | 0/442 (0.0%) | 3/154 (1.9%) | 0.017 | | Pulmonary Edema | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Repeat Surgery | 0/442 (0.0%) | 2/154 (1.3%) | 0.066 | | Surgical Wound Adverse Event | 0/442 (0.0%) | 2/154 (1.3%) | 0.066 | | Total Major Adverse Events Patients | 7/442 (1.6%) | 8/154 (5.2%) | 0.030 | SSED P000039 {7} Table 1 Adverse Events - Pivotal Study (continued) | Minor Adverse Events | AMPLATZER Patients | Surgical Control Patients | p-value | | --- | --- | --- | --- | | Anemia | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Allergic reaction (drug) | 2/442 (0.5%) | 0/154 (0.0%) | 1.00 | | Atelectasis | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Cardiac Arrhythmias Minor Treatment | 15/442 (3.4%) | 9/154 (5.8%) | 0.23 | | Device Embolization with percutaneous removal | 1/442 (0.2%) | 0/154 (0.0%) | 1.00 | | Extremity Tingling/Numbness | 1/442 (0.2%) | 0/154 (0.0%) | 1.00 | | Headaches/Possible TIA | 2/442 (0.5%) | 0/154 (0.0%) | 1.00 | | Delivery System Failure | 2/442 (0.5%) | 0/154 (0.0%) | 1.00 | | Pericardiotomy Syndrome | 0/442 (0.0%) | 2/154 (1.3%) | 0.066 | | Pericardial effusion | 0/442 (0.0% | 6/154 (3.9%) | <0.001 | | Pleural Effusion | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Pneumothorax | 0/442 (0.0%) | 3/154 (1.9%) | 0.017 | | Staph Infection | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Surgical Wound Adverse Events | 0/442 (0.0%) | 1/154 (0.6%) | 0.26 | | Thrombus formation | 3/442 (0.7%) | 0/154 (0.0%) | 0.56 | | Transfusions | 0/442 (0.0%) | 2/154 (1.3%) | 0.066 | | Upper Respiratory Infection/Fever | 0/442 (0.0%) | 2/154 (1.3%) | 0.066 | | Urinary Tract Disturbance | 1/424 (0.2%) | 0/154 (0.0%) | 1.00 | | Total Minor Adverse Events (Patients) | 27/442 (6.1%) | 29/154 (18.8%) | <0.001 | Table 2: Adverse Events -FF | | AMPLATZER Patients | Upper 95% Confidence Bound | | --- | --- | --- | | Major Adverse Events | | | | Repeat Surgery | 1/48 (2.1%) | 0.095 | | Hemothorax | 1/48(2.1%) | 0.095 | | Minor Adverse Events | | | | Vomiting (required 2 nights in hospital) | 1/48 (2.1%) | 0.095 | | Atrial fibrillation/cardioversion | 1/48 (2.1%) | 0.095 | | Total Adverse Events | 4/48 (8.3%) | 0.181 | # 8.2 Potential Adverse Events Placement of the AMPLATZER Septal Occluder involves using standard interventional cardiac catheterization techniques. The following adverse events (listed in alphabetical order) might be expected from interventional cardiac catheterization techniques. Air embolus - Allergic dye reaction - Anesthesia reactions Apnea Fever SSED P000039 {8} - Hypertension/hypotension - Infection including endocarditis - Perforation of vessel or myocardium - Pseudoaneurysm including blood loss requiring transfusion - Valvular regurgitation ## 9. Summary Of Preclinical Studies ### 9.1 Bench Testing Bench testing was done to ensure that all initial design requirements were met. Bench testing has demonstrated the strength and reliability of the device. Design verification of the device and its components has been conducted to verify that the device is safe for its intended use. SSED P000039 {9} Table 3 Summary of AMPLATZER Septal Occluder Testing | Test | Samples | | Specification | Results | | | | --- | --- | --- | --- | --- | --- | --- | | Pull Test Laser Weld – Marker Bands to Wire Braid | Wire Dia. | N | .004 - .006" diameter wire >12 lbs | Wire diameter | Mean ±SD (range) lbs | | | | .004" | 9 | | .004" | 30.3 ± 2.6 (26.3-35.5) | | | | .005" | 10 | .007" diameter wire >24 lbs | .005" | 36.79 ± 3.3 (32.9 - 40) | | | | .006" | 11 | | .006" | 37.6 ± 3.8 (29.9 - 42.6) | | | | .007" | 5 | .008" diameter wire >32.2 lbs | .007" | 49.8 ± 6.2 (41.2 - >55) | | | | .008" | 5 | | .008" | All samples exceeded 55 lbs | | | Pull Test Laser Weld- Screw Attachment to Marker Bands | Wire Dia. | N | .004 - .006" diameter wire >12 lbs | Wire Diameter | Mean ±SD (range) lbs | | | | .004" | 5 | | .004" | 34.8 ± 7.6 (28.3-45.3) | | | | .005" | 7 | .007" diameter wire >24 lbs | .005" | 38.3 ± 5.8 (31.1 - 47) | | | | .006" | 10 | | .006" | 47.9 ± 4.9 (34.95 - >50) | | | | .007" | 5 | .008" diameter wire >32.2 lbs | .007" | 49.8 ± 6.2 (41.2 - >55) | | | | .008" | 5 | | .008" | All samples exceeded 55 lbs | | | Pull Test Delivery Cable screw and device end screw | 5 | | 12 lbs | Mean ±SD (range) lbs 26.4 ± 2.3 (23.4 - 29.15) | | | | Device Integrity | 1 | | Structural Integrity must remain intact. | Structural integrity remained intact when single and multiple wires were cut, as well as when the left atrial disc post was cut. | | | | Life Cycle | 300 (30 each of the smallest & largest device in each of the wire diameters) | Structural integrity must remain intact after 400 million cycles | Size | Wire dia. | # Fail | | | | | | 4 | .004" | 0 | | | | | | 10 | .004" | 0 | | | | | | 11 | .005" | 0 | | | | | | 17 | .005" | 2¹ | | | | | | 18 | .006" | 0 | | | | | | 24 | .006" | 1 | | | | | | 26 | .007" | 0 | | | | | | 34 | .007"² | 0 | | | | | | 34 | .008" | 0 | | | | | | 40 | .008" | 0 | | ¹ In both cases, the devices had retained their preset shape and had to be compressed several times to detect the broken wires. If a wire were to fracture in the clinical setting, it would not protrude due to the shape memory property of Nitinol. ² Initially, the 34mm device was manufactured with .007" wire. It was later changed to .008" wire. SSED P000039 {10} Table 4 Summary of AMPLATZER Delivery System Testing | Test | Samples | | Specification | Results | | | --- | --- | --- | --- | --- | --- | | Delivery Sheath Kink Resistance | Size | N | The sheath must not kink during normal clinical use. | Size | Mean ± SD (range) degrees | | | 6F | 4 | | 6F | 131.3 ± 4.8 (125 – 135) | | | 7F | 4 | | 7F | 118.8 ± 2.5 (115 – 120) | | | 8F | 4 | | 8F | 112.5 ± 6.5 (105 – 120) | | | 9F | 4 | | 9F | 112.5 ± 2.9 (110 – 115) | | | 10F | 5 | | 10F | 106 ± 5.5 (100 – 110) | | | 12F | 5 | | 12F | 129 ± 4.2 (125 – 135) | | Delivery Cable Kink Resistance | 10 | | The cable must not kink during normal clinical use. | Mean ± SD (range) degrees 128.5 ± 7.8 (120-145) | | | Pull Tests - Delivery Sheath Hub to Tubing | Size | N | Pull strength must not be <3lbs. | Size | Mean ± SD (range) lbs | | | 6F | 4 | | 6F | 8 ± 1.3 (6.85 – 9.25) | | | 7F | 4 | | 7F | 10.5 ± 0.1 (10.3 – 10.7) | | | 8F | 4 | | 8F | 11.3 ± 0.1 (11.3 – 11.5) | | | 9F | 4 | | 9F | 11.6 ± 0.1 (11.5 – 11.8) | | | 10F | 5 | | 10F | 14.3 ± 0.1 (14.2 – 14.4) | | | 12F | 5 | | 12F | 17.3 ± 1.0 (16.2 – 18.7) | | Pull Test - Delivery Cable - Cable to Cable Screw Weld Joint | 10 | | 12 pounds | Mean ± SD (range) lbs 46.1 ± 5.5 (37 - >50) | | ## 9.2 MRI Compatibility Two AMPLATZER Septal Occluders were placed in a water phantom, fixed with adhesive tape, and examined by a Siemens 1.5 Tesla MRI apparatus. Various imaging modalities were used and minimal artifacts were only observed in the object vicinity. The device is MRI safe up to 1.5 Tesla. ## 9.3 Corrosion Testing ### 9.3.1 Corrosion – Bench Testing The device was tested per ASTM F746. The Nitinol sample did not display the general pitting found on the 316SS sample. In addition, there was no indication of crevice corrosion on the nickel-titanium sample as was seen on the 316 SS samples. Eight devices were tested for corrosion potential. The devices were degreased, rinsed with deionized water and blown with dry air. The electrolyte was prepared by dissolving 36.9g reagent grade sodium chloride in deionized water. After transfer to the corrosion cell, the electrolyte was deoxygenated by sparging with zero grade nitrogen for a minimum of 60 minutes. The devices were suspended in the corrosion cell and maintained in the electrolyte at open circuit for 60 minutes before beginning the polarization SSED P000039 {11} scan (0.6 V/h). The electrochemistry was performed with a PAR 263 Potentiosatat. In all devices the onset of corrosion occurred ca. 0.08 V from the open circuit potential. The corrosion potential (E_CORR) for the samples tested varied by ca. 0.08 V. The shape of the hysteresis curve indicates that localized corrosion may occur. ## 9.3.2 Corrosion – Animal Testing Post mortem examination was conducted in an animal specimen wherein two devices were implanted (device #1 – implanted 18 months and device #2 implanted 14 months). Although the animal was implanted with the AMPLATZER Muscular Ventricular Septal Occluder device, materials and methods are identical to the AMPLATZER Septal Occluder. Analysis revealed both devices were nearly covered by neoendocardium. Gross inspection revealed no wire breakage. Light microscopy at 40x revealed a smooth surface. Scanning electron microscopy was carried out and compared to a new control wire. Both surfaces appear identical. The wire surface appearance was typical of oxidized Nitinol wire. Both devices were weighed (275 mg and 156 mg). No evidence of corrosion was observed for either device. ## 9.3.3 Abrasion A device was explanted from a swine after 3 months (at least 26 million cycles). A biopsy was taken from the neo-endocardium for histologic examination. The device was examined grossly, by light microscopy and by scanning electron microscopy (SEM). No broken wires were detected. SEM examination was made at randomly selected wire intersection on both the large and small discs. The typical condition of the wires at the intersections was photographed. Results indicate that there are no signs of intersecting wires abrading each other. ## 9.4 Biocompatibility Tests The AMPLATZER Septal Occluder is constructed of Nitinol (a nickel-titanium alloy) and polyester. Sufficient information from the literature exists to demonstrate biocompatibility of the Nitinol for use in an implantable device.³,⁴,⁵ SSED P000039 {12} The polyester fabric and the patient contacting components of the delivery system underwent biocompatibility testing in accordance with FDA General Program Memorandum G95-1, which provides an FDA-modified matrix of International Standard ISO 10993, "Biological Evaluation of Medical Devices Part 1: Evaluation and Testing." Table 5 – Summary of Biocompatibility Testing | Test | Result | | | --- | --- | --- | | | Polyester Fabric | Delivery System | | Cytotoxicity | Pass | Pass | | Sensitization | Non-sensitizer | Non-sensitizer | | Hemolysis | Non hemolytic | Non-hemolytic | | Intracutaneous Injection (Irritation) | Pass | Pass | | Toxicity | Pass (Subchronic) | Pass (Systemic) | | Acute Systemic Injection | Pass | Not required | | Ames Salmonella Mutagenicity | No mutagenic activity | Not required | | Implantation | Moderate reaction* | Not required | | Chronic Toxicity | Pass | Not required | *A “moderate reaction” is exactly what is expected when tissue ingrowth is the desired result. ## 9.5 Useful Life (Sterilization/Shelf Life) The AMPLATZER Septal Occluder and Delivery System are single-use devices which are provided sterile (via ethylene oxide) to the user. The sterilization cycle was validated to ensure successful sterilization to a Sterility Assurance Level (SAL) of $10^{-6}$. Product and package stability testing of the AMPLATZER Septal Occluder and Delivery System was performed. Visual inspection and physical testing indicated that the device performed within product specification for up to 3 years. Based upon these results, an expiration date of 3 years has been established. ## 9.6 Animal Testing Animal studies were conducted to evaluate the device design and to demonstrate that the AMPLATZER Septal Occluder was capable of providing rapid closure and endothelialization of atrial septal defects without evidence of residual shunting. Twelve (12) Yucatan minipigs underwent surgical creation of an atrial septal defect and were allowed to recover for 10 – 14 days. The animals were then implanted with the AMPLATZER Septal Occluder. Sequential angiographic studies and blood gas measurements were repeated at one week, one month and three month intervals. The animals were then euthanized with removal of the heart and lungs for gross and histologic examination. SSED P000039 {13} At 3 months all animals studied exhibited complete endothelialization by neoendothelium. This tissue in-growth demonstrated that the device was firmly fixed into position and was covered by a glistening non-thrombogenic layer of cells. In this final state, it was apparent that no thrombosis, shunting or dislodgment occurred. ## 10. Summary Of Clinical Studies ### 10.1 Objective The objective of the study was to compare the clinical performance of the AMPLATZER Septal Occluder device for atrial septal defect (ASD) closure with that documented for the ASD Surgical Repair Procedure. A Registry Group was also studied to evaluate the device in patients with Fenestrated Fontan. ### 10.2 Study Design A multi-center, non-randomized, controlled clinical study was performed to evaluate the safety (incidence of major adverse events) and effectiveness (closure of the defect defined as ≤ 2mm shunt) of the AMPLATZER Septal Occluder. #### Pivotal Study Enrolled patients had echocardiographic evidence of ostium secundum atrial septal defect (device group: defect size ≤ 38mm) and clinical evidence of right ventricular volume overload or had clinical symptoms such as paradoxical embolism or atrial dysrhythmia in the presence of a minimal shunt. Exclusion criteria included: - Patients with multiple defects that could not be adequately covered by the device (device group only). - Associated congenital cardiac anomalies requiring surgery. - Ostium primum or sinus venosus atrial septal defects. - Partial anomalous pulmonary venous drainage. - Pulmonary vascular resistance above 7 Woods units or a right-to-left shunt at the atrial level with a peripheral arterial saturation < 94%. - Patients with recent myocardial infarction, unstable angina and decompensated congestive heart failure. - Patient with right and/or left ventricular decompensation with ejection fraction < 30%. - Sepsis. - History of repeated pulmonary infection. - Any type of serious infection < 1 month prior to procedure. - Malignancy where life expectancy was < 2 years. - Demonstrated intracardiac thrombi on echocardiography. - Weight < 8 Kilograms. - Inability to obtain informed consent. SSED P000039 {14} - Patients with gastritis, gastric ulcer, duodenal ulcer, bleeding disorders etc. and other contraindications to aspirin therapy unless other anti-platelet agents can be administered for 6 months. ## Registry Group The inclusion criteria for the Registry group were: - Fenestrated Fontan (communication in the baffle with at least 5mm distance from the free atrial wall and central venous pressure less than 15Hg). ## 10.3 Patient Description and Accountability Patients were enrolled into the pivotal study from March 1998 through March 2000 at 29 centers in the United States. Device placement was attempted in 442 patients. In 18 patients the device was recaptured prior to releasing from the delivery cable due to anatomical conditions. There was one acute embolization. Thus 423 patients received 433 devices. ASD surgical data was collected prospectively in 117 patients and retrospectively in 37 patients. Table 6: Patient Baseline Demographics | Variable | | AMPLATZER Patients | Surgical Control Patients | p-value | | --- | --- | --- | --- | --- | | Age (years) | Mean±s.d.(N) [range] | 18.1 ± 19.3 (442) [0.6, 82.0] | 5.9 ± 6.2 (154) [0.6, 38.2] | <0.001 | | Gender | | | | | | Female | | 299/442 (67.6%) | 94/154 (61.0%) | 0.14 | | Male | | 143/442 (32.4%) | 60/154 (39.0%) | | | Height (cm) | Mean±s.d.(N) [range] | 134.6 ± 32.0 (440) [58,188] | 105.5 ± 26.9 (151) [60,178] | <0.001 | | Weight (kg) | Mean±s.d (N) [range] | 42.3 ±27.3 (440) [6.3,130] | 20.6 ± 15.2 (153) [4.8,78.4] | <0.001 | | Medical History | | | | | | CHF | | 11/442 (2.5%) | 7/154 (4.5%) | 0.27 | | Failure to Thrive | | 14/442 (3.2%) | 13/154 (8.4%) | 0.012 | | CAD | | 9/442 (2.0%) | 0/154 (0%) | 0.12 | | Respiratory Infections | | 7/442 (1.6%) | 13/154 (8.4%) | <0.001 | | TIA | | 6/442 (1.4%) | 1/154 (0.6%) | 0.68 | | COPD | | 1/442 (0.2%) | 0/154 (0%) | 1.00 | | Hypertension | | 16/442 (3.6%) | 0/154 (0%) | 0.016 | | Stroke | | 13/442 (2.9%) | 0/154 (0%) | 0.026 | | Recurrent Strokes/TIA’s | | 5/442 (1.1%) | 1/154 (0.6%) | 1.00 | | Diabetes | | 4/442 (0.9%) | 0/154 (0%) | 0.58 | SSED P000039 {15} Table 7: Pre-Closure –Fenestrated Fontan | Age (years) | Mean±s.d (N) [range] | 7.8 ± 6.9 (48) [1.6, 44.9] | | --- | --- | --- | | Gender: Female | | 29/48 (60.4%) | | Height (cm) | Mean±s.d.(N) [range] | 114.5 ± 25.2 (46) [78,168] | | Weight (kg) | Mean±s.d (N) [range] | 22.4 ± 13.5 (48) [9.7, 68.7] | | Medical History: | | | | CHF | | 1/48 (2.1%) | | Failure to thrive | | 1/48 (2.1%) | | Stroke | | 2/48 (4.2%) | | Heart Murmur | | 26/47 (55.3%) | | Pulmonary Ejection Murmur | | 2/47 (4.3%) | | Mid Diastolic Murmur | | 1/47 (2.1%) | | Right axis deviation | | 11/45 (24.4%) | | Peaked p waves | | 1/45 (2.2%) | | Cardiomegaly | | 20/45 (44.4%) | ## 11. Data Analysis and Results Patients with ostium secundum atrial septal defects and clinical evidence of right ventricular volume overload who were being evaluated for ASD closure underwent physical examination which included: heart murmur classification; an electrocardiogram (EKG) to document cardiac electrical characteristics; a chest x-ray to evaluate heart size and pulmonary vasculature; a detailed 2D Color Doppler Transthoracic Echo (TTE) to evaluate the atrial septal defect location, number of ASD’s, size of the ASD’s, and distance from the ASD to the coronary sinus, pulmonary vein, and AV valves. The patients were instructed to avoid strenuous activity for a period of one month and to take aspirin for 6 months post placement (3-5mg/kg/day). Additionally, patients were examined and a transthoracic Echocardiogram (TTE) was conducted at 24 hours, 6 months and 1 year. Post-discharge data was collected in surgical patients when available. Ninety-four (94) surgical repair patients were confirmed to be closed by echo at 12 months. All were assumed closed at 12 months. Trivial and small shunts were considered hemodynamically insignificant. An independent core lab assessed a subset of echo videotapes for 12-month shunt status; a Data Safety Monitoring Board adjudicated all adverse events. SSED P000039 {16} Table 8: Principal Effectiveness and Safety Results - Pivotal Study | | AMPLATZER Patients1 | Surgical Control Patients | 90% Confidence Interval | | --- | --- | --- | --- | | Technical Success | 423/442 (95.7%) | 154/154 (100.0%) | (-0.084,-0.010) | | Procedure Success | 413/423 (97.6%) | 154/154 (100.0%) | (-0.059, +0.008) | | Early (≤ 30 days) Composite Success | 401/442 (90.7%) | 148/154 (96.1%) | (-0.111, -0.005) | | 12-month Composite Success | 331/362 (91.4%) | 146/154 (94.8%) | (-0.096, +0.019) | | 24-hour Closure Success | 404/418 (96.7%) | 154/154 (100%) | (-0.073, -0.001) | | 6-month Closure Success | 376/387 (97.2%) | 154/154 (100%) | (-0.068, +0.003) | | 12-month Closure Success | 326/331 (98.5%) | 149/149 (100%) | (-1.052, 0.017) | | | | | | | Principal Safety Measures | | | | | Major Adverse Events 12-months | 7/442 (1.6%) | 8/154 (5.2%) | (-0.090, -0.002) | | Minor Adverse Events 12-months | 27/442 (6.1%) | 29/154 (18.8%) | (-0.200, -0.070) | | 12-month Composite Success (K-M) | 0.934 | 0.938 | [-0.077, +0.036] | | Survival at 30 days (K-M) | 0.939 | 0.956 | [-0.052, +0.018] | | Survival at 180 days (K-M) | 0.936 | 0.947 | [-0.048, +0.026] | Table 9: Principal Effectiveness and Safety Results - Pivotal Study Patient Age $< {20}$ years | | AMPLATZER Patients | Surgical Control Patients | 90% Confidence Interval | | --- | --- | --- | --- | | Technical Success | 315/328 (96.0%) | 149/149 (100%) | (-0.086, -0.005) | | Procedure Success | 306/315 (97.1%) | 149/149 (100%) | (0.074, +0.005) | | Early (≤ 30 days) Composite Success | 295/328 (89.9%) | 143/149 (95.9%) | (-0.124, -0.007) | | 12-month Composite Success | 256/281 (91.1%) | 142/149 (95.3%) | (-0.108, +0.013) | | 24-hour Closure Success | 301/310 (97.1%) | 149/149 (100%) | (-0.075, +0.005) | | 6-month Closure Success | 270/278 (97.1%) | 149/149 (100%) | (-0.077, +0.006) | | 12-month Closure Success | 246/251 (98.0%) | 149/149 (100%) | (-0.068, +0.014) | | | | | | | Principal Safety Measures | | | | | Major Adverse Events 12-months | 6/328 (1.8%) | 7/149 (4.7%) | (-0.086, +0.008) | | Minor Adverse Events 12-months | 16/328 (4.9%) | 29/149 (19.5%) | (-0.221, -0.085) | | 12-month Composite Success (K-M) | 0.930 | 0.944 | [-0.055, +0.027] | | Survival at 30 days (K-M) | 0.933 | 0.954 | [-0.059, +0.017] | | Survival at 180 days (K-M) | 0.930 | 0.954 | [-0.062, +0.014] | 1Unit of analysis $=$ Patient. Although 10 patients had 2 defects each treated with an AMPLATZER Septal Occluder; all patients with multiple AMPLATZER implants were successfully treated. Technical Success: successful deployment of the device, or the successful completion of the surgical procedure. Procedure Success: successful closure of the defect as measured immediately following the procedure $(\leq 2\mathrm{mm}$ residual shunt) Composite Success: All device placement attempts without a major adverse event, surgical reintervention, embolization, technical failure or major shunt (defined as $>2\mathrm{mm}$ ). Closure Success: among patients that were technical successes, closure of the atrial septal defect (defined as a shunt $\leq 2\mathrm{mm}$ ) without the need for surgical repair. SSED P000039 {17} Major Adverse Events: Events that are life threatening, prolong hospitalization or have long-term consequences or need for ongoing therapy. These include but are not limited to cerebral embolism, cardiac perforation with tamponade, endocarditis, pericardial effusion with tamponade, repeat surgery, death, cardiac arrhythmias requiring permanent pacemaker placement or long term anti-arrhythmic medication and device embolizations requiring immediate surgical removal. Minor Adverse Events: Device embolization with percutaneous retrieval, cardiac arrhythmia with treatment, phrenic nerve injury, hematoma, other vascular access site adverse events, retroperitoneal hematoma, surgical wound adverse events, other procedural adverse events, pericardial effusion requiring medical management, evidence of device associated thrombus formation without embolization (with or without treatment) and marker band embolization without known sequelae. Table 9: Principal Efficacy Results—FF | PRINCIPAL EFFECTIVENESS RESULTS | AMPLATZER Patients | Lower 95% Confidence Bound | | --- | --- | --- | | Technical Success | 46/48 (95.8%) | 0.875 | | Procedure Success | 46/46 (100.0%) | 0.937 | | Early Composite Success | 44/48 (91.7%) | 0.819 | | 6 month Success | 38/38 (100.0%) | 0.924 | | Primary Efficacy Outcome (12 month Success) | 32/32 (100.0%) | 0.911 | | Hospital days Mean±s.d. (N) [range] | 1.2±0.7 (39) [0.0, 4.0] | (0.95, 1.41) | Table 10: Principal Safety Results – FF | PRINCIPAL EFFECTIVENESS RESULTS | AMPLATZER Patients^{1} | Upper 95% Confidence Bound | | --- | --- | --- | | Major Adverse Events | 2/48 (4.2%) | 0.125 | | Minor Adverse Events | 2/48 (4.2%) | 0.125 | | Total Adverse Events | 4/48 (8.3%) | 0.181 | 1Unit of analysis = patient ## 12. Device Failures and Replacements Device: Reported device failures include deformed upon deployment (“cobra”) and immediate device embolization Delivery System: Marker band embolization, sheath kink/accordion, and leaking hubs have been reported for the delivery system. ## 13. Conclusions Drawn From The Studies ### 13.1 Atrial Septal Defects SSED P000039 {18} Effectiveness of the AMPLATZER Septal Occluder for treatment of atrial septal defects has been demonstrated by: - Successful closure of ASD's at 12-month follow-up without the need for additional surgical repair in 326 out of 331 patients. - These results are statistically equivalent to the 100% rate reported for the ASD Surgical Repair Control group. The Lower 95% confidence bound for the difference in 12-month success rate is -1.052, which is greater than the protocol specified requirement of -.08. - The adverse event rates associated with the use of the AMPLATZER device at 12 months are within the protocol-defined acceptable limits. The mortality rate for the device cohort was 0%, which is less than the proposed 2%; the major adverse event rate for AMPLATZER patients was 1.6%, which is less than the proposed 10% rate. The overall AMPLATZER adverse event rate (7.2%) was statistically significantly lower than that reported for the control group (24.0%) (p = <0.001). - In addition to a high rate of effectiveness and a low risk of major adverse events, the mean length of hospital stay for AMPLATZER patients of 1 day is statistically significantly lower than the mean of 3.4 days documented for the ASD Surgical Repair control group (p <0.001). ## 13.2 Fenestrated Fontan Effectiveness of the AMPLATZER Septal Occluder for treatment of Fenestrated Fontans has been demonstrated by: - Results consistent with those obtained for treatment of ASD. - Primary Efficacy Outcome at 12 months follow-up without the need for additional surgical repair in 32 of 32 patients, obviates the need for a second surgical procedure in this patient population. - The adverse event rates associated with the use of the AMPLATZER device at 12 months are within the protocol-defined acceptable limits. The mortality rate for the device cohort was 0%, which is less than the proposed 2%; the major adverse event rate for AMPLATZER patients was 4.2%, which is less than the proposed 10% rate. In conclusion, the AMPLATZER® device operates as designed and is safe and effective in the clinical environment in the intended patient population and is appropriate for market release. SSED P000039 {19} SSED Page 19 P000039 ## 14. Panel Recommendation At an advisory meeting held on September 10, 2001, the Circulatory System Devices recommended that Amplatzer® ASO System be approved subject to the submission to, and approval by, the Center for Devices and Radiological Health (CDRH) the following: - changes to the labeling for the Amplatzer® ASO System; - items to be incorporated into the training program; and - collection of 5-year follow-up data for patients enrolled in the clinical investigations contained in the PMA. ## 15. CDRH Decision CDRH concurred with the Circulatory System Devices Panel recommendation of September 10, 2001, and conveyed the Conditions of Approval in a facsimile dated November 11, 2001. AGA Medical indicated concurrence with those Conditions of Approval. FDA issued an approval order on _______________. The applicant’s manufacturing facility was inspected on October 30, 2000 and contract sterilization facility was inspected on May 1, 2001. These facilities were found to be in compliance with the device Good Manufacturing Practice regulations. ## 16. Approval Specifications Indications for Use: See the Instructions for Use (Attachment 1) Hazards to Health from use of the Device: See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE EVENTS in the Instructions for Use (Attachment 1). Postapproval requirements and restrictions: See approval order. The Approval Order, Summary of Safety and Effectiveness Data, and labeling can be found on the Internet at address _______________. --- **Source:** [https://fda.innolitics.com/device/P000039](https://fda.innolitics.com/device/P000039) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com