ANGIOJET RHEOLYTIC THROMBECTOMY LF140 CATHETER
Device Facts
| Record ID | P980037 |
|---|---|
| Device Name | ANGIOJET RHEOLYTIC THROMBECTOMY LF140 CATHETER |
| Applicant | Boston Scientific Corp |
| Product Code | MCX · Cardiovascular |
| Decision Date | Mar 12, 1999 |
| Decision | APPR |
| Device Class | Class 3 |
| Attributes | Therapeutic, Expedited Review |
Indications for Use
The AngioJet System is intended for removing thrombus in the treatment of patients with symptomatic coronary artery or saphenous vein graft lesions in vessels ≥ 2.0 mm in diameter prior to balloon angioplasty or stent placement.
Device Story
AngioJet Rheolytic Thrombectomy System comprises single-use LF140 catheter, single-use pump set, and multi-use drive unit. Catheter is 140 cm, 5.0 French, dual-lumen, over-the-wire device. Operates via Bernoulli effect: high-velocity saline jets directed backward create localized low-pressure zone at distal tip, inducing suction to break up and evacuate thrombus through exhaust lumen. Used in cardiac catheterization labs by interventional cardiologists. System tracks over standard 0.018-inch guide wire. Output is thrombus removal from coronary conduits. Clinical benefit includes reduction of thrombus burden prior to definitive revascularization (angioplasty/stenting), potentially reducing distal embolization and improving procedural success compared to thrombolytic infusion. Healthcare providers monitor procedure via angiography and ECG; output directly facilitates subsequent stent/balloon placement.
Clinical Evidence
Prospective, multi-center clinical trials (VeGAS 1 feasibility, VeGAS 2 randomized trial, AMI/TE treatment arms) enrolled 731 patients. Randomized trial (n=349) compared AngioJet to urokinase. Primary endpoint (composite of death, Q-wave MI, emergent CABG, TLR, CVA, or stent rethrombosis at 30 days) showed 70.9% success for AngioJet vs 70.4% for urokinase. AngioJet demonstrated higher device success (87.4% vs 75.3%) and lower bleeding/vascular complications. MACE (CK-MB) at 30 days was 15.6% for AngioJet vs 32.5% for urokinase. Preclinical evidence included bench testing, biocompatibility (ISO 10993), ex vivo porcine/human graft models, and canine in vivo studies.
Technological Characteristics
Dual-lumen catheter (5.0F, 140cm). Materials: 304L stainless steel (hypotubing, tip, manifold), titanium (ferrule), Pebax (shaft), polycarbonate/silicone (manifold). Energy source: high-pressure saline (6,700-10,300 psi). Connectivity: mechanical connection to drive unit/pump. Sterilization: sterile, single-use. Principle: Bernoulli-effect rheolytic thrombectomy. Software: None (mechanical system).
Indications for Use
Indicated for patients with symptomatic coronary artery or saphenous vein graft lesions in vessels ≥ 2.0 mm in diameter requiring thrombus removal prior to balloon angioplasty or stent placement. Contraindicated in patients contraindicated for other intracoronary interventional procedures or where the lesion cannot be accessed with a guide wire.
Submission Summary (Full Text)
{0}
AngioJet LF140 Catheter SSED...page 1
# Summary of Safety and Effectiveness Data
## AngioJet® Rheolytic™ Thrombectomy System
### Table of Contents
1. General Information...2
2. Indications and Usage...2
3. Contraindications...2
4. Warnings and Precautions...2
5. Device Description...3
Figure 1. AngioJet LF140 Catheter...3
6. Alternative Practices or Procedures...3
7. Marketing History...3
8. Adverse Events...4
5.1 Observed Adverse Events...4
Table 1. Clinical Trial Patient Enrollment...4
Table 2. Major Adverse Events (to 30 Days)...5
9. Summary of Preclinical Studies...7
9.1 Laboratory Studies...7
Table 3: Physical and Functional Testing for the AngioJet LF140 Catheter...8
Table 4: Physical and Functional Testing for the AngioJet Pump Set...8
Table 5: Critical Bond Testing for the AngioJet LF140 Catheter System...9
Table 5: Critical Bond Testing for the AngioJet Pump Set...9
9.2 Biocompatibility Testing...9
Table 7: Biocompatibility Testing for the AngioJet LF140 Catheter...10
Table 8: Biocompatibility Testing for the AngioJet Pump Set...10
Table 9: Materials for the AngioJet LF140 Catheter...11
Table 10: Materials for the AngioJet Pump Set...11
9.3 Animal Studies...12
9.4 Additional Studies...13
10. Summary of Clinical Studies...13
10.1 Overview...13
10.2 Objectives...13
10.3 Study design...13
10.4 Description of Patients and Gender Bias...14
10.5 Results:...14
Table 11. Principal Effectiveness and Safety Results...15
Figure 2. MACE (CK-MB)-Free Survival...16
10.6 Device Failures...16
Table 12. Device Failures...16
11. Conclusions Drawn from the Studies...17
12. Panel Recommendation...17
13. FDA Decision...17
14. Approval Specifications...17
{1}
# Summary of Safety and Effectiveness Data
AngioJet® Rheolytic™ Thrombectomy System
Possis Medical, Inc.
## 1. General Information
Device Generic Name: Percutaneous coronary thrombectomy catheter system (Class III)
Device Trade Name: AngioJet® Rheolytic™ Thrombectomy LF140 Catheter
AngioJet® Drive Unit
AngioJet® Pump Set
Applicant's Name and Address: Possis Medical, Inc.
9055 Evergreen Blvd. N.W.
Minneapolis, Minnesota 55433-8003
PMA Application Number: P980037
Date of Panel Recommendation: None
Date of Notice of Approval to the Applicant: March 12, 1999
## 2. Indications and Usage
The AngioJet System is intended for removing thrombus in the treatment of patients with symptomatic coronary artery or saphenous vein graft lesions in vessels ≥ 2.0 mm in diameter prior to balloon angioplasty or stent placement.
## 3. Contraindications
Do not use the AngioJet LF140 Catheter in patients:
- Who are contraindicated for other intracoronary interventional procedures, as the device only removes thrombus in preparation for balloon angioplasty or stent placement.
- In whom the lesion cannot be accessed with the guide wire.
## 4. Warnings and Precautions
See WARNINGS AND PRECAUTIONS in the final draft labeling (Information for Use)
AngioJet LF140 Catheter SSED...page 2
{2}
# 5. Device Description
Figure 1. AngioJet LF140 Catheter
The AngioJet® LF140 Rheolytic™ Thrombectomy Catheter (AngioJet LF140 Catheter) is one component of the AngioJet® Rheolytic™ Thrombectomy System (AngioJet System). The other two components are the single-use AngioJet® Pump Set and the multi-use AngioJet® Drive Unit (both packaged and sold separately). The AngioJet LF140 Catheter may only be used in conjunction with the AngioJet Pump Set and AngioJet Drive Unit.
The AngioJet LF140 Catheter is a 140 cm, 5.0 French, dual lumen, sterile, single-use catheter designed for removing thrombus from coronary conduits. High velocity saline jets directed back into the catheter create a localized low pressure zone at the distal tip (Bernoulli effect) which results in the suction, break-up, and removal of thrombus through the exhaust lumen.
The AngioJet LF140 Catheter is introduced through a guide catheter. An 8 French high flow guide catheter (0.080 inch minimum internal diameter) is sufficient to allow passage of the AngioJet LF140 Catheter with adequate clearance for injection of standard contrast media, if desired. The AngioJet LF140 Catheter tracks and operates over a standard 0.018 inch (or smaller) guide wire.
# 6. Alternative Practices or Procedures
Alternative treatments include intravenous or intra-arterial infusion of thrombolytic drugs such as tissue plasminogen activator, streptokinase, or urokinase to lyse the thrombus. Other mechanical treatments include: intracoronary balloon angioplasty, intracoronary stenting, and a device, which uses rotating cutting blades at the catheter tip.
# 7. Marketing History
The AngioJet System (all components including the AngioJet LF140 Catheter) has been marketed in the U.S. for a different indication (treatment of thrombosed dialysis access grafts) since December 1996 under premarket notification K960970.
LF140 Catheter has been marketed for coronary artery treatment in Australia, Austria, Switzerland, Canada, France, Germany, Greece, India, Italy, Netherlands, Norway, Portugal, Russia, and Saudi Arabia
There have been no countries from which the device has been withdrawn from marketing for any reason related to safety or effectiveness of the device.
AngioJet LF140 Catheter SSED... page 3
{3}
# 8. Adverse Events
## 5.1 Observed Adverse Events
A total of 731 patients were enrolled in two multi-center clinical trials of the AngioJet System, as summarized in Table 1.
Table 1. Clinical Trial Patient Enrollment
All patients in all Clinical Studies (n=731)
| Study Group | Feasibility patients (AngioJet) | VeGAS 2 Randomized Study | | |
| --- | --- | --- | --- | --- |
| | | AngioJet patients | Urokinase (control) | Total VeGAS 2 Patients |
| Vein Graft AngioJet Study (VeGAS 1 feasibility study) | 90 | | - | |
| VeGAS 2 Randomized Trial:
Qualification phase | 80 | | - | |
| Randomization phase | - | 180 | 169 | 349 |
| VeGAS 2 AMI Treatment Arm | - | 107 | - | 107 |
| VeGAS 2 TE Treatment Arm | - | 105 | - | 105 |
| Patient Totals | 170 | 392 | 169 | 561 |
Adverse events from the second Vein Graft AngioJet Study (VeGAS 2) Randomized Trial (AngioJet treatment arm), the Acute Myocardial Infarction (AMI) Treatment Arm, and the Thrombolysis Exclusion (TE) Treatment Arm are shown in Table 2 (n= 561 patients).
AngioJet LF140 Catheter SSED... page 4
{4}
All patients in the VeGAS 2 Randomized Trial, AMI Treatment Arm, and TE Treatment Arm (n=561)
Table 2. Major Adverse Events (to 30 Days)
% (number) difference [95% confidence interval]
| | Randomized Trial | | | AMI Treatment Arm
n=107 | TE Treatment Arm
n=105 |
| --- | --- | --- | --- | --- | --- |
| | AngioJet Arm
(n=180) | Urokinase Arm
(n=169) | Difference
[95% CI] | | |
| Death | 1.7% (3) | 3.0% (5) | -1.3% [-4.5, 1.9]¹ | 7.5% (8) | 1.9% (2) |
| MACE | 13.9% (25) | 21.9% (37) | -8.0% [-16.0, 0.0] | 13.1% (14) | 18.1% (19) |
| MACE (CK-MB) | 15.6% (28) | 32.5% (55) | -17.0% [-25.8, 8.2] | 13.1% (14) | 23.8% (25) |
| MI | 11.1% (20) | 19.5% (33) | -8.4% [-16.0, -0.9] | 3.7% (4) | 14.3% (15) |
| Q-MI | 2.2% (4) | 5.3% (9) | -3.1% [-7.1, 0.9] | 0.0% (0) | 1.0% (1) |
| Non-Q-MI | 8.9% (16) | 14.2% (24) | -5.3% [-12.0, 1.4] | 3.7% (4) | 14.3% (15) |
| MI (CK-MB) | 14.4% (26) | 30.8% (52) | -16.3% [-25.0, -7.7] | 3.7% (4) | 20.0% (21) |
| Q-MI | 2.2% (4) | 5.3% (9) | -3.1% [-7.1, 0.9] | 0.0% (0) | 1.0% (1) |
| Non-Q-MI | 12.2% (22) | 25.4% (43) | -13.2% [-21.3, -5.1] | 3.7% (4) | 20.0 (21) |
| TLR (TOTAL) | 3.3% (6) | 3.6% (6) | -0.2% [-4.0, 3.6] | 2.8% (3) | 5.7% (6) |
| CABG | 0.6% (1) | 3.0% (5) | -2.4% [-5.2, 0.4] | 0.9% (1) | 0.0% (0) |
| PTCA | 2.8% (5) | 0.6% (1) | 2.2% [-0.5, 4.9] | 1.9% (2) | 5.7% (6) |
| Abrupt Closure | 3.3% (6) | 4.7% (8) | -1.4% [-5.5, 2.7] | 4.7% (5) | 5.7% (6) |
| Subacute Closure | 2.8% (5) | 4.1% (7) | -1.4% [-5.2, 2.5] | 1.9% (2) | 6.7% (7) |
| Bleeding Complication | 5.0% (9) | 11.8% (20) | -6.8% [-12.7, -1.0] | 13.1% (14) | 12.4% (13) |
| Vascular Complication | 4.4% (8) | 17.8% (30) | -13.3% [-19.8, -6.8] | 12.1% (13) | 9.5% (10) |
| CVA | 1.7% (3) | 1.2% (2) | 0.5% [-2.0, 3.0] | 1.9% (2) | 1.0% (1) |
MACE = Death, Q wave and non-Q wave MI (CPK > 2X upper limit normal), emergent CABG, repeat target lesion revascularization, or CVA within 30 days of index procedure, as determined by the Clinical Events Committee.
MACE (CK-MB) = Death, Q wave and CK-MB non-Q wave MI (CK-MB > 3X upper limit normal), emergent CABG, repeat target lesion revascularization, or CVA within 30 days of index procedure, as determined by the Clinical Events Committee.
MI includes non-Q wave MI = CPK > 2X upper limit normal
AngioJet LF140 Catheter SSED...page 5
{5}
MI (CK-MB) includes non-Q wave MI = CK-MB > 3X upper limit normal
TLR= Target lesion revascularization.
Abrupt Closure = lesion-related new severely reduced flow (TIMI 0 or 1) within the target vessel that persisted, and required rescue by a non-assigned treatment strategy, or persisted and resulted in MI or death.
Subacute closure = new reduced (TIMI 0 or 1) flow at the target vessel as a result of a mechanical obstruction, such as dissection or luminal thrombus, occurring after completion of the index procedure but within 30 days of the index procedure.
Bleeding Complications = procedure related blood transfusions.
Vascular Complications = hematoma > 4cm, retroperitoneal bleed, false aneurysm, AV fistula, peripheral ischemia/nerve injury, hemolysis and hemolytic anemia.
¹ Difference = SAngioJet - Surokinase, SEdiff = sqrt(SEAngioJet² + SEurokinase²), CI = Diff + 1.96*SEdiff
Total Deaths: There were a total of 44 deaths among the 731 patients in all clinical studies. All deaths were reviewed by a masked, independent clinical events committee (ICEC). None of the deaths were judged by the ICEC to be directly attributable to the device. During the Feasibility Study 12 patient deaths occurred, four within 30 days of the assigned treatment (two due to cardiac arrest, and one each due to cardiogenic shock and intracerebral hemorrhage and cardiac arrest). In the Randomized Trial, 16 patients died, six in the AngioJet arm (one patient never received the assigned treatment) and ten in the urokinase treatment arm. Of the five patients that were treated with the AngioJet, the two deaths within 30 days were due to respiratory distress / electromechanical dissociation (n=1), and cardiomyopathy / congestive heart failure (n=1). The other three deaths occurred between 98 and 317 days post AngioJet treatment due to respiratory failure (n=1), and sudden cardiac death (n=2). Ten AMI Treatment Arm patients died during the study. The eight deaths which occurred within 30 days were due to cardiac arrest (n=4), cardiac tamponade (n=1), cardiogenic shock (n=1), myocardial rupture (n=1), and pericardial effusion / heart block (n=1). Six TE Treatment Arm patients died during the study. The two deaths within 30 days were due to cardiac arrest (n=1) and cardiogenic shock (n=1).
## 5.2 Potential Adverse Events
Potential adverse events (in alphabetical order) which may be associated with use of the AngioJet LF140 Catheter including those listed in Table 2 and the following:
- abrupt closure of treated vessel
- acute myocardial infarction
- arrhythmias, including VF and VT
- death
- dissection
- emboli, distal
- emergent CABG
- hemolysis
- hemorrhage, requiring transfusion
- hypotension/hypertension
- infection at the access site
- myocardial ischemia
- pain
- perforation
- pseudoaneurysm
AngioJet LF140 Catheter SSED... page 6
{6}
- reactions to contrast medium
- stroke/CVA
- thrombosis/occlusion
- total occlusion of treated vessel
- vascular spasm
## 9. Summary of Preclinical Studies
### 9.1 Laboratory Studies
#### In Vitro Studies
In vitro studies were conducted early in design development to assess AngioJet LF140 Catheter performance in simulated use models. Assessments focused on the following parameters: clot cutting rate-axial speed at which the Catheter could be advanced through clot with complete removal of the clot; particle analysis- evaluation of size and relative percentage of proximal and distal embolic particles resulting from Catheter operation; and hemolysis resulting from Catheter operation. These baseline studies proved the AngioJet LF140 Catheter to be acceptable for further design verification studies and subsequent evaluation in animal models.
#### Design Verification Studies
Evaluation of critical design parameters was performed with AngioJet System during the design verification phase of product development. Functional testing included evaluation of critical performance parameters, simulated use testing, and critical bond testing. The physical and functional tests performed on the AngioJet LF140 Catheter and AngioJet Pump Set are summarized in Tables 3 and 4. Test results met the acceptance criteria in all cases.
AngioJet LF140 Catheter SSED...page 7
{7}
Table 3: Physical and Functional Testing for the AngioJet LF140 Catheter
| Test Parameter | Acceptance Criteria | Samples | Results [Mean + SD (Range)] | Results |
| --- | --- | --- | --- | --- |
| Flow Rate – saline volume per time delivered by Catheter | 47-53 ml/min | 5 Catheters | 49.0 ± 0.7 ml/min (48-50 ml/min) | All passed |
| Stagnation Pressure - outflow lumen pressure | 60 psi minimum | 5 Catheters | 68.4 ± 3.2 psi (65-73 psi) | All passed |
| Net Evacuation Rate - difference between evacuated and infused volume per time | -8 to 18 ml/min with guide wire | 5 Catheters | -3.2 ± 1.2 ml/min [(-1.8)-(-4.4) ml/min] | All passed |
| Push/Track Force - force needed to insert and advance catheter | 1.0 lbf. maximum | 5 Catheters | 0.24 ± 0.06 lbf. (0.20-0.34 lbf.) | All passed |
| Pressurized Bend Test - minimum curvature in distal segment of pressurized catheter | Minimum of 0.5 cm bend radius over 180° without failure | 5 Catheters | No failures recorded | All passed |
| Pressurized Torque Test – over-rotation along Catheter length without failure | 720° rotation from tip to manifold without failure | 5 Catheters | No failures recorded | All passed |
| High Pressure Test - sustained Catheter operation at high pressure | 17,000 psi for 60 seconds without failure | 5 Catheters | No failures recorded | All passed |
| Operating Pressure - system pressure caused by Catheter | 6,700-10,300 psi | 5 Catheters | 7,290 ± 213 psi (7,000-7,500 psi) | All passed |
| Dynamic Pressure - exhaust pressure at the roller pump | 20-65 psi | 5 Catheters | 49 ± 4.2 psi (45-55 psi) | All passed |
Table 4: Physical and Functional Testing for the AngioJet Pump Set
| Test Parameter | Acceptance Criteria | Samples Tested | Results [Mean + SD (range)] | Results |
| --- | --- | --- | --- | --- |
| Pump Prime Time – time for pump to self prime | Prime time is 45 sec maximum | 30 Pump Sets | 14 ± 4.16 seconds (8-30 seconds) | All passed |
| Pump Volume (Mode 2) – volume of saline per time delivered by the pump | 47 ml/min minimum 53 ml/min maximum | 15 Pump Sets | 48.6 ± 0.71 ml/minute (48-50 ml/minute) | All passed |
| Pump Leakage - presence of saline at a connection point | Leak proof at 18,000 psi for 1 min minimum | 15 Pump Sets | No leaks | All passed |
| Check Valve Seal Test – saline leak at connection points | Leak proof at 18,000 psi for 1 min minimum | 15 Pump Sets | No leaks | All passed |
| Pump Life - total run time before pump failure | 20 min minimum | 16 Pump Sets | 138 ± 46 minutes (43-199 minutes) | All passed |
| Supply Line Pressure - pressure test to verify leak-tight assembly | Leak proof at 18,000 psi for 5 sec minimum | 110 Pump Sets | No leaks | All passed |
Critical bond test results for the AngioJet LF140 Catheter and AngioJet Pump Set are summarized in Tables 6 and 7. Test results met the acceptance criteria in all cases.
AngioJet LF140 Catheter SSED...page 8
{8}
AngioJet LF140 Catheter SSED...page 9
Table 5: Critical Bond Testing for the AngioJet LF140 Catheter System
| Test Parameter | Acceptance Criteria | Samples Tested | Results [Mean + SD (Range)] | Results |
| --- | --- | --- | --- | --- |
| Distal Catheter Tip-to-Pebax | 2.2 lbf. minimum | 5 subassemblies | 7.56 ± 0.17 lbf. (7.337-7.745 lbf.) | All passed |
| Manifold-to-Pebax | 1.0 lbf. minimum | 5 Catheters | 5.241 ± 0.202 lbf. (4.969-5.479 lbf.) | All passed |
| Hypotube-to-Filter Housing | 4.0 lbf. minimum | 15 Catheters | 12 ± 1.36 lbf. (9.39-13.95 lbf.) | All passed |
| Cap-to-Loop | 3.37 lbf. minimum | 37 Catheters | 4.988 ± 0.926 lbf. (3.791-7.635 lbf.) | All passed |
| Inner Body-to-Hypotube | 2.0 lbf. minimum | 15 Catheters | 3.59 ± 0.759 lbf. (2.685-5.329 lbf.) | All passed |
Table 5: Critical Bond Testing for the AngioJet Pump Set
| Test Parameter | Acceptance Criteria | Samples Tested | Results [Mean + SD (Range)] | Results |
| --- | --- | --- | --- | --- |
| Spike Assembly-to-Inflow Line Tensile Test | 4.0 lbf. minimum | 30 Pump Sets | 18.3 ± 1.05 lbf. (13.9-19.3 lbf.) | All passed |
| Bag Drop Impact Test | Survive 6 feet drop with 1800 ml in bag | 15 Pump Sets | No leaks | All passed |
| Inflow Line-to-Pump Tensile Test | 2.0 lbf. minimum | 15 Pump Sets | 16.6 ± 2.4 lbf. (8.8-18.0 lbf.) | All passed |
| Pump Piston -to-Boot and Prime Cup-to-Boot Tensile Test | 1.0 lbf. minimum | 30 Pump Sets | 11.3 ± 2.8 lbf. (4.9-17.9 lbf.) | All passed |
| Pump-to-Supply Line Tensile Test | 18.5 lbf. minimum | 15 Pump Sets | 54.9 ± 4.3 lbf. (48.3-65.8 lbf.) | All passed |
| Supply Line-to-Quick Connect Nut Tensile Test | 18.5 lbf. minimum | 15 Pump Sets | 38.6 ± 9.1 lbf. (28.8-51.2 lbf.) | All passed |
| Outflow Line-to-Male Luer Pressure Test | Hold 90 psi for 30 sec minimum | 10 Pump Sets | No failures | All passed |
| Outflow Line-to-Female Luer Pressure Test | Hold 90 psi for 30 sec minimum | 10 Pump Sets | No failures | All passed |
| Bag Tubing-to-Luer Tensile Test | 5.0 lbf. minimum | 16 Pump Sets | 44.1 ± 1.26 lbf. (41.5-45.7 lbf.) | All passed |
| Bag Tubing-to-Bag Tensile Test | 5.0 lbf. minimum | 13 Pump Sets | 33.2 ± 3.42 lbf. (26.8-38.1 lbf.) | All passed |
| Bag Tubing-to-Luer Pressure Test | 100 psi minimum for 20 min | 15 Pump Sets | No leaks | All passed |
| Paratube Male Luer Tensile Test | 5.0 lbf. minimum | 20 Pump Sets | 20.8 ± 0.91 lbf. (26.8-38.1 lbf.) | All passed |
| Paratube Female Luer Tensile Test | 5.0 lbf. minimum | 20 Pump Sets | 25.9 ± 0.86 lbf. (23.1-27.1 lbf.) | All passed |
## 9.2 Biocompatibility Testing
Tables 8 and 9 summarize results of the biocompatibility tests performed on the AngioJet LF140 Catheter and the AngioJet Pump Set, as recommended in ISO 10993: Biological Evaluation of
16
{9}
Medical Devices (performed on AngioJet Catheters and subassemblies). All samples passed all screening tests after exposure to the manufacturing process conditions.
Table 7: Biocompatibility Testing for the AngioJet LF140 Catheter
| Test Protocol | Sample | Result |
| --- | --- | --- |
| Cytotoxicity- cultured mouse L929 fibroblast cells exposed to MEM media. Catheter material extract*. | 1device | passed |
| Hemolysis- fresh rabbit blood incubated with 10ml of Catheter material extract, using 0.9% saline media. Adapted from ASTM 756-82 and ASTM 619. | 1device | passed |
| Systemic Toxicity- mice injected with Catheter material extract using 0.9% saline, USP alcohol, PEG, and cottonseed oil media, per USP XXII, p. 1497 and USP- NF, p. 2703. | 1device | passed |
| Intracutaneous Toxicity- rabbits injected with Catheter material extract using 0.9% saline, USP alcohol, PEG, and cottonseed oil media, per USP XXII, p. 1497 and USP- NF, p. 2703. | 4 devices | passed |
| Carcinogenicity / Genotoxicity- Salmonella typhimurium and mouse L5178Y/TK lymphoma cells exposed to Catheter material extract using 0.9% saline and DMSO media per Ames Salmonella Mutagenicity Assay, and *Health Effects Guideline 476 (Genetic Toxicology: in vitro mammalian cell gene mutation tests,) April 1984, published by OECD. | 2 devices | passed |
| Dermal Sensitization- Guinea pigs intradermally injected with Catheter material extract using Freund's complete adjuvant, per Magnusson and Linkgman, Allergic Contact Dermatitis, * Identification of Contact Allergans,* 1970, and USP XXII, p. 1497. | 1device | passed |
| Subchronic Toxicity- mice dosed 5 days with daily hematology and homeostatic evaluations, and gross necropsy at 14 days, per Page and Sawhney, *Proceedings of the Workshop on Subchronic Toxicity Testing,* 1980. | 1device | passed |
| Pyrogenicity- material mediated pyrogen testing per USP biological test <151>. | 3 devices | passed |
| Intramuscular Irritant Implant- 30 day intramuscular Catheter extract material implant in rabbits. | 4 devices | passed |
| Skin Irritation Implant- Modified Draize Test, ASTM F719-81, Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation | 1device | passed |
* Extraction method per USP <87>, XXII, as recognized by TC 194 (ISO 10993-12).
Table 8: Biocompatibility Testing for the AngioJet Pump Set
| Test Description | Sample | Results |
| --- | --- | --- |
| Cytotoxicity- Cultured mouse L929 fibroblast cells exposed to MEM media (Pump material extract*) | 1 device | Passed |
| Hemolysis- Fresh rabbit blood incubated with 10ml of Pump material extract, using 0.9% saline media (adapted from ASTM 756-82 and ASTM 619) | 1 device | Passed |
| Systemic Toxicity- Mice injected with Pump material extract using 0.9% saline, USP alcohol, PEG, and cottonseed oil media, per USP XXII, p. 1497 and USP NF, p. 2703 | Saline flow pathway materials | Passed |
| Irritation or Intracutaneous Toxicity- Guinea pigs were sensitized to 0.9% saline extracts of Pump material and subsequently exposed to pump materials. Procedures referenced: Magnusson & Kligman, 1970, and USP XXII, pages 1497-1499. | Saline flow pathway materials | Passed |
| Subchronic Toxicity- Mice dosed 5 days with daily hematology and homeostatic evaluations, and gross necropsy at 14 days, per Page and Sawhney, *Proceedings of the Workshop on Subchronic Toxicity Testing*, 1980. | 1 device | Passed |
| Pyrogenicity- Material mediated pyrogen testing per USP biological test <151>. | 3 devices | Passed |
The materials used in the blood/ tissue contact and sterile fluid path of the AngioJet LF140 Catheter and AngioJet Pump Set have a history of safety, strength, and biocompatibility in short-
AngioJet LF140 Catheter SSED... page 10
{10}
term use devices currently being marketed in the USA and internationally. The blood/tissue contact and sterile fluid path component materials are listed in Table10 and 11, respectively.
Table 9: Materials for the AngioJet LF140 Catheter
| Component | Material |
| --- | --- |
| High Pressure Saline Inflow Path | 304L stainless steel hypotubing, tip, manifold fitting; titanium ferrule |
| Catheter Shaft | Medical grade Pebax (polyether block amide) |
| Catheter Manifold | Medical grade Polycarbonate, silicone |
| Assembly Adhesives | Medical grade cyanoacrylate |
Table 10: Materials for the AngioJet Pump Set
| Component | Material |
| --- | --- |
| Outlet Adapter | 303/304 stainless steel |
| Pump Sleeve | Polytetrafluoroethylene (PTFE)* |
| Silicone Ring | Medical grade silicone* |
| High pressure seal | Polyethylene* |
| Pump Housing | 17-4 stainless steel* |
| Pump Filter | 316 stainless steel* |
| Prime Sensor Cup | Polycarbonate* |
| Pump Boot | Medical grade silicone* |
| Check Valve Ball | 304/316 stainless steel* |
| O-ring | Vinylidene Fluoride Hexafluoropropylene* |
| Pump Ferrule | Titanium* |
| Valve Block | 17-4 stainless steel* |
| Retaining Collar | 304 stainless steel |
| Supply Line Retainer | Titanium* |
| Nut | Polypropylene, 18-8 stainless steel |
| Supply Line | 304L stainless steel* |
| Compression Spring | 304 stainless steel* |
| Inlet Block | 316 stainless steel* |
| Spike | Medical grade ABS plastic* |
| Drip Chamber | PVC plastic* |
| Tubing | Medical grade PVC plastic* |
| Tubing Clamp | Medical grade polypropylene |
| Spike Filter | Polypropylene/PTFE* |
| Paratubing | Medical grade PVC plastic |
| Heat Shrink Ring | (FEP) |
| Piston Head | 6061 Aluminum |
| Piston | 17.4 stainless steel* |
* Fluid Pathway
## Ex Vivo Studies
Testing was performed to evaluate possible injury to the vessel wall during AngioJet LF140 Catheter operation in an ex vivo porcine arterial model. Fifteen Catheters were tested. The results showed that treatment effects were limited to focal endothelial cell denudation and few mild focal disruptions of the internal elastic lamina. Similar findings were also observed with passage of guide catheters and guide wires in the ex vivo model.
The AngioJet LF140 Catheter was also evaluated in an ex vivo human coronary bypass graft model using excised thrombotic saphenous vein grafts obtained from patients at the time of repeat bypass surgery. Four grafts and AngioJet LF140 Catheters were tested. The results showed no
AngioJet LF140 Catheter SSED... page 11
{11}
angiographic or histologic evidence of graft intimal dissection.
## 9.3 Animal Studies
Safety and effectiveness of the AngioJet System were evaluated in vivo in a canine model with treatment of simulated arterial thrombus. Twelve AngioJet LF140 Catheters were used to treat 10 coronary arteries, 10 peripheral arteries (femoral and renal) and five femoral veins in 12 dogs. Controls included sham Catheter treatment and vessel instrumentation with guide catheters and wires only. PTCA was also performed for comparison. In all cases, the AngioJet LF140 Catheter functioned properly and was successfully advanced to the target site using standard techniques. There were no perforations or observable hemorrhages caused by the Catheter, even when thrombolytic drugs were infused following Catheter treatment. Gross, histologic, and scanning electron microscopy (SEM) examination of explanted vessels revealed no serious injury to the vessel wall. There were no obvious differences between baseline, final procedure, and where applicable, four week and six month angiograms, ECGs, or ventriculograms.
A mild to moderate increase in serum free hemoglobin was observed following AngioJet System operation (baseline = 40.4 +/- 17.9 mg/dL; post-treatment operation = 643.3 +/- 270.9 mg/dL, mean Catheter operation time = 4.7 minutes); however, serum free hemoglobin returned to normal levels 1-4 days following operation. Blood urea nitrogen (BUN) and creatinine levels were within normal limits at all times and there were no significant effects of AngioJet System-related hemolysis noted.
In studies to simulate AngioJet LF140 Catheter treatment of a coronary thrombus, the total CK rose very little, while there was a slight increase in CK-MB (total CK, baseline = 168 IU/L; total CK, post- Catheter treatment = 571.5 IU/L-- largely attributed to surgical cutdown to establish vascular access; CK-MB, baseline = 1.25 ng/dL; peak CK-MB post- treatment = 5.65ng/dL). Thus, a slight amount of myocardial damage could not be excluded.
These studies demonstrated safety of the AngioJet System in an animal model, and provided the basis for clinical evaluation.
## 9.3.1 Clinical Relevance
Clinical use of the AngioJet System has shown that in some cases, arrhythmias and temporary heart block, requiring treatment with a temporary pacemaker, may occur during Catheter operation. The occurrence of arrhythmia has been noted especially during Catheter operation in the distal circulation supplying the AV node. Similar electrophysiologic aberrations have also been noted during coronary rotational atherectomy procedures. Animal testing was conducted using a porcine model to evaluate the mechanism for the generation of arrhythmias and heart block, which had not been previously observed in the canine studies. The results of these screening studies led to the hypothesis that heart block may be caused by localized transient increases in adenosine-- a cellular component of blood cells released during AngioJet LF140 Catheter-associated hemolysis-- and mediated by adenosine receptors on the SA and AV nodes. This hypothesis was supported by testing that showed a reduction in the incidence of heart block from 94% to 17% when subjects (N=8 pigs) were treated prior to device activation with aminophylline, a competitive antagonist for the adenosine receptor.
AngioJet LF140 Catheter SSED... page 12
{12}
AngioJet LF140 Catheter SSED...page 13
## 9.4 Additional Studies
Independent testing laboratories tested the AngioJet® Drive Unit according to the UL Standard for Safety of Medical and Dental Equipment (UL 544) and the IEC 60601-1 General Safety Standard and found it to be free from safety hazards and in compliance with the requirements of these standards.
An independent testing laboratory tested the AngioJet® Drive Unit according to FCC Class B and IEC 60601-1-2 Conducted and Radiated Mode and found it to be free from electromagnetic radiation hazards and in compliance with the requirements of these standards.
An independent testing laboratory tested the AngioJet® Drive Unit according to Clause 17h of EN 60601-1:1990 (defibrillation-proof safety) and found it to be in compliance with the requirements of that standard.
## 10. Summary of Clinical Studies
### 10.1 Overview
As summarized in Table 1, a total of 731 patients were enrolled in two multi-center trials of the AngioJet System with the LF140 Catheter under an approved IDE.
### 10.2 Objectives
The purpose of the Vein Graft AngioJet study was to establish the safety and effectiveness of thrombus removal by the AngioJet LF140 Catheter in saphenous vein bypass grafts or native coronary arteries ≥ 2.0 mm in diameter. The Randomized Trial was configured as a multicenter, 2-arm prospective trial comparing immediate AngioJet thrombectomy to urokinase thrombolysis (infusion for 6 to 30 hours), followed by definitive percutaneous treatment of the lesion.
### 10.3 Study design
The primary endpoint for the Randomized Trial and the AMI and TE treatment arms was defined as occurrence of death, Q wave MI, emergent CABG, target lesion revascularization, CVA, or stent rethrombosis by 30 days; or failure to achieve a post-procedure diameter stenosis < 50%, or failure to achieve post-procedure TIMI 3 flow, or to achieve a ≥ 20% change in diameter stenosis.
Baseline clinical and angiographic data were collected to establish angiographic evidence of thrombus. Clinical follow-up was required at 30 days, six months, and one year. Quantitative coronary angiography was performed pre-procedure, following thrombectomy, and after final treatment. Endpoints for all clinical studies were immediately analyzed on an intent-to-treat basis. An independent Clinical Events Committee adjudicated all major adverse events.
{13}
AngioJet LF140 Catheter SSED...page 14
## 10.4 Description of Patients and Gender Bias
The Randomized Trial was designed to evaluate 520 patients, but was stopped after 349 patients were enrolled because of a growing imbalance in some safety outcomes and increased difficulty in maintaining enrollment rates. The study population included patients with angiographically evident thrombus in either a saphenous vein bypass graft or a native coronary artery ≥ 2.0 mm in diameter who had not experienced an AMI within 24 hours. Patients who warranted percutaneous revascularization of one or two discrete thrombotic lesions within the same target vessel were eligible for enrollment. Patients experiencing an AMI (within 24 hr of symptom onset) were eligible for enrollment in an AMI Treatment Arm. Diagnosis of AMI was based on clinical symptoms, ECG evidence of ischemic ST changes, and elevated cardiac enzymes. Patients ineligible for enrollment in the randomized trial due to contraindications for urokinase thrombolysis were eligible for enrollment in the TE Treatment Arm.
The Randomized Trial and AMI and TE Treatment Arms enrolled patients of both genders. Of the 561 patients enrolled, 444 (79%) were male. This proportion of males (444/117 = 3.79) reflects the general referral pattern for patients undergoing percutaneous coronary intervention for symptomatic coronary artery disease. Analyses of efficacy and safety outcomes show that differences between the genders in pre-treatment reference vessel diameter in patients who received randomized AngioJet treatment resulted in outcome differences in post-procedure device success and minimum lumenal diameter. In addition, the rate of bleeding complications was higher in women in the TE Treatment Arm. No other variables examined showed a difference by gender.
## 10.5 Results:
The clinical trials enrolled patients with any duration of symptoms. Of the 440 patients reporting a duration of symptoms before AngioJet treatment, 135 (31%) reported symptoms less than 24 hours, 269 (61%) had symptom duration of 24 hours to two weeks, and 36 (8%) had symptoms lasting more than two weeks. Procedure success was 81%, 83%, and 75% for these three symptom duration categories, compared to 62%, 75%, and 63% for the same duration categories treated with the urokinase control. Examination of these results by lesion site (SVG vs. native) and post procedure minimum lesion diameter (MLD) did not show any interaction.
Table 11 shows the principal effectiveness and safety outcomes for the randomized cohort and the AMI and TE Treatment Arms. The primary endpoint for the trial combined efficacy measures at the end of treatment with freedom from major complications at 30 days. Results for this endpoint did not differ between randomized treatments (70.9% for AngioJet compared to 70.4% for urokinase).
{14}
Table 11. Principal Effectiveness and Safety Results
All Randomized, AMI, and TE Treatment Arm Patients Treated (561 Patients, 565 Lesions)
| Cohort | AngioJet RCT (N=180) | Urokinase RCT (N=169) | % Difference (95% C.I.) | AMI Arm (N=107) | TE Arm (N=105) |
| --- | --- | --- | --- | --- | --- |
| Efficacy Measures | | | | | |
| Lesion Success | 87.6% (156/178) | 79.6% (129/162) | 8.0 [0.1, 15.9] | 83.0% (88/106) | 77.9% (81/104) |
| Procedure Success | 86.3% (151/175) | 72.2% (117/162) | 14.1 [5.5, 22.6] | 77.1% (81/105) | 76.0% (79/104) |
| Device Success | 87.4% (153/175) | 75.3% (122/162) | 12.1 [3.9, 20.4] | 82.9% (87/105) | 76.9% (80/104) |
| Post-Procedure MLD (mm)
Range (min, max) | 2.59±0.82 (178)
(0.00, 5.42) | 2.45±1.08 (162)
(0.00, 4.70) | 0.14 [-0.1, 0.3] | 2.41±0.81 (106)
(0.00, 4.12) | 2.61±1.03 (104)
(0.00, 4.80) |
| Post-Procedure % DS
Range (min, max) | 22%±21% (178)
(-30%, 100%) | 28%±29% (162)
(-31%, 100%) | -6.0 [-11.3, -0.7] | 24%±24% (106)
(-37%, 100%) | 24%±27% (104)
(-32%, 100%) |
| TLR-Free at 30 Days | 96.7% | 96.4% | 0.2 [-3.6, 4.1] | 97.1% | 94.2% |
| TVR-Free at 30 Days | 95.0% | 95.8% | -0.8 [-5.2, 3.6] | 96.2% | 93.2% |
| TVF-Free at 30 Days | 85.0% | 77.5% | 7.5, -0.7, 15.6] | 86.0% | 81.8% |
| MACE (CK-MB) Free at 30 Days | 84.4% | 67.5% | 17.0 [8.1, 25.8] | 86.9% | 76.1% |
| Primary Endpoint-Free at 30 Days | 70.9% (124/175) | 70.4% (114/162) | 0.5 [-9.2, 10.2] | 75.2% (79/105) | 68.9% (71/103) |
| Safety Measures | | | | | |
| In-Hospital MACE (CK-MB) | 14.4% (26/180) | 32.5% (55/169) | 0.44 [0.30, 0.66] | 13.1% (14/107) | 20.0% (21/105) |
| Out-of-Hospital MACE (CK-MB)
to 30 Days | 3.9% (7/180) | 1.2% (2/169) | 3.29 [0.76, 14.23] | 0.0% (0/107) | 6.7% (7/105) |
| Abrupt Closure | 3.3% (6/180) | 4.7% (8/169) | 0.70 [0.25, 1.98] | 4.7% (5/107) | 5.7% (6/105) |
| Subacute Closure | 2.8% (5/180) | 4.1% (7/169) | 0.67 [0.22, 2.06] | 1.9% (2/107) | 6.7% (7/105) |
| Bleeding Complications | 5.0% (9/180) | 11.8% (20/169) | 0.42 [0.20, 0.88] | 13.1% (14/107) | 12.4% (13/105) |
| Vascular Complications | 4.4% (8/180) | 17.8% (30/169) | 0.25 [0.13, 0.49] | 12.1% (13/107) | 9.5% (10/105) |
| CVA to 30 Days | 1.7% (3/180) | 1.2% (2/169) | 1.41 [0.24, 8.27] | 1.9% (2/107) | 1.0% (1/105) |
Numbers are % (counts/sample size) and Mean±Standard Deviation.
CI = Confidence Interval.
Relative Risk = AJ/UK
SE = sqrt((1 - p₁)/n₁₁ + (1 - p₂)/n₂₁)
CI = RR*exp(±1.96*SERR)
Difference = AJ-UK
SE = sqrt(p₁*p₁/n₁ + p₂*p₃/n₂)
CI = Diff±1.96*SEDiff
Lesion Success = Achievement of a final residual diameter stenosis of <50% (by QCA core laboratory), and TIMI 3 flow post-procedure using any percutaneous method.
Procedure Success = Achievement of a final residual diameter stenosis of <50% (by QCA core laboratory), and TIMI 3 flow post-procedure in the absence of death, emergent bypass surgery, or Q wave MI prior to hospital discharge as determined by the independent Clinical Events Committee.
Device Success = Achievement of a final residual diameter stenosis of <50% (by QCA core laboratory), and TIMI 3 flow post-procedure, using the assigned device only (without crossover use of AngioJet in patients randomized to urokinase).
Minimal Lumen Diameter = Mean minimum lumen diameter using the "worst view" analysis method.
Diameter Stenosis (DS) = 100% X (1-[MLD/RVD]), based on the mean value from 2 orthogonal views (when available) using QCA.
TLR-free = No target lesion revascularization.
TVR-free = No target vessel revascularization.
TVF-free = No death, Q wave and WHO non-Q wave MI, or target vessel revascularization.
In-Hospital MACE (CK-MB) = Death, Q wave and non-Q wave (CK-MB > 3X upper limit normal) MI, emergent CABG, repeat target lesion revascularization, or CVA prior to hospital discharge as determined by the independent Clinical Events Committee.
Out-of-Hospital MACE (CK-MB) = Death, Q wave and non-Q wave (CK-MB > 3X upper limit normal) MI, emergent CABG, repeat target lesion revascularization, or CVA after hospital discharge as determined by the independent Clinical Events Committee.
Primary Endpoint Free at 30 Days = No death, Q wave MI, emergent CABG, target lesion revascularization, CVA, or stent thrombosis to 30 days as determined by the independent Clinical Events Committee, with TIMI 3 flow and DS <50% post-procedure, and a ≥0.20 change in diameter stenosis.
Bleeding Complications = Procedure related blood transfusions.
Vascular Complications = Hematoma >4 cm, retroperitoneal bleed, false aneurysm, AV fistula, peripheral ischemia/nerve injury, hemolysis and hemolytic anemia.
*Survival estimates by Kaplan-Meier method; Standard Error estimates by Greenwood formula:
Difference = S_AJ - S_UK
SE_Diff = sqrt(SE_AJ^2 + SE_UK^2)
CI = Diff±1.96*SEDiff
AngioJet LF140 Catheter SSED...page 15
{15}
Non-Q wave MI is an indicator of distal embolization and myocardial necrosis. MACE (CK-MB) is a composite of Death, Q wave and non-Q wave (CK-MB > 3X upper limit normal) MI, emergent CABG, repeat target lesion revascularization, or CVA. Figure 2 displays Kaplan-Meier actuarial curves of MACE (CK-MB)-free survival out to one year for the two treatments.
Figure 2. MACE (CK-MB)-Free Survival
Kaplan-Meier estimates and ± 1.5 standard errors of the mean
All Randomized Patients Treated (349 Patients)
Numbers of
Patients at 30 days 90 days 180 days 270 days 360 days
AngioJet 152 142 130 120 95
Urokinase 114 105 94 87 73
## 10.6 Device Failures
Table 12 summarizes the device failures reported during the clinical trials. AngioJet Drive Units and Pump Set failures are also noted. In no case did a device failure jeopardize patient health or treatment.
Table 12. Device Failures
| Failure Mode | Randomized Trial | AMI Treatment Arm | TE Treatment Arm | Qualifying Patient Arm | TOTAL |
| --- | --- | --- | --- | --- | --- |
| Mechanical drive unit failure | 1 | 1 | 1 | 0 | 3 |
| Pump set failure | 0 | 2 | 2 | 0 | 4 |
| Unable to deliver Catheter | 4 | 6 | 2 | 2 | 14 |
AngioJet LF140 Catheter SSED...page 16
{16}
# 11. Conclusions Drawn from the Studies
The preclinical laboratory evaluation of the AngioJet verified that it performed to design specification and provided adequate evidence of biocompatibility, sterility and shelf life. The *in vivo* preclinical studies demonstrated safety adequate to begin clinical evaluation.
In the randomized clinical trial, AngioJet treatment demonstrated lower rates than the control for major adverse cardiac events at both 30 days and 6 months follow-up. Safety outcomes for the two non-randomized registries did not differ significantly from the AngioJet randomized treatment arm.
AngioJet treatment was associated with higher acute clinical and angiographic success than with the control.
The foregoing results support the benefits of use of the AngioJet System for the target population outweigh the risk of illness or injury when used as indicated in accordance with the information for use.
# 12. Panel Recommendation
In accordance with the provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Circulatory System Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.
# 13. FDA Decision
FDA issued an approval order to Possis Medical, Inc. advising that its PMA was approved. See Approval Order
FDA performed an inspection and found the applicant in compliance with the Quality System Regulation (21 CFR Part 820).
# 14. Approval Specifications
Directions for Use: See Final Draft Labeling (Information for Use)
Hazards to Health from Use of the Device: See INDICATIONS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE EVENTS in the Final Draft Labeling (Information for Use).
Post-approval Requirements and Restrictions: See Approval Order
AngioJet LF140 Catheter SSED... page 17
