← Product Code [MGB](/productcode/MGB) · P050043 # FEMORAL INTRODUCER SHEATH AND HEMOSTASIS (FISH) DEVICE 5,6, AND 8 FRENCH (P050043) _Morris Innovative Research, Inc. · MGB · Aug 20, 2007 · Cardiovascular · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P050043 ## Device Facts - **Applicant:** Morris Innovative Research, Inc. - **Product Code:** [MGB](/productcode/MGB.md) - **Decision Date:** Aug 20, 2007 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Cardiovascular - **Attributes:** Therapeutic ## Indications for Use The Femoral Introducer Sheath and Hemostasis Device (FISH™ Device) is intended for hemostatic closure of femoral artery access sites. The system is indicated for use in reducing time to hemostasis and time to ambulation in patients who have undergone diagnostic procedures using 5, 6, or 8 French procedural sheaths. ## Device Story FISH™ is a vascular closure device utilizing a patch of porcine-derived ExtraCellular Matrix (ECM) pre-mounted on a sheath introducer. The device is supplied in a sterile kit including access needle, guide wire, and pre-dilator. During use, the ECM patch is deployed at the femoral artery puncture site to facilitate hemostasis. The device is operated by a physician in a clinical setting. By providing a biological scaffold for tissue repair, the device reduces time to hemostasis and time to ambulation compared to manual compression, potentially improving patient comfort and enabling earlier hospital discharge. The healthcare provider uses the device to close the access site immediately following catheter removal; the output is the achieved hemostasis, which directly affects the patient's recovery timeline and mobility. ## Clinical Evidence Prospective, randomized, multi-center clinical trial (N=206 diagnostic patients) comparing FISH™ (n=139) to manual compression (n=67). Primary safety endpoint: MACE rate non-inferiority (delta 5%). Primary effectiveness endpoints: time to hemostasis (TTH) and time to ambulation (TTA). Results: Median TTH 6 min (FISH) vs 17 min (control) (p<0.0001); Median TTA 2.0 hrs (FISH) vs 4.2 hrs (control) (p<0.0001). MACE rate 0.72% (FISH) vs 0% (control). Minor adverse events 2.88% (FISH) vs 1.49% (control). ## Technological Characteristics Materials: Porcine Small Intestinal Submucosa (SIS) containing collagen (Types I, III, VI), glycosaminoglycans, proteoglycans, and glycoproteins. Components: Sheath introducer, ECM patch, access needle, guide wire, pre-dilator. Sterilization: Ethylene Oxide (EtO). Packaging: Tyvek™ covered PEG tray. Mechanical testing: Burst pressure, leak testing, and retention strength validated against ASTM/ISO standards. ## 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} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA ## I. GENERAL INFORMATION Device Generic Name: Femoral Introducer Sheath Hemostasis Device Device Trade Name: FISH™ Device Applicant: MIR Corporation 907 W. Second St. Bloomington, IN 47403 Premarket Approval (PMA) Application Number: P050043 Date of Panel Recommendation: None Date of Notice of Approval to Applicant: August 20, 2007 ## II. INDICATIONS FOR USE The Femoral Introducer Sheath and Hemostasis Device (FISH™ Device) is intended for hemostatic closure of femoral artery access sites. The system is indicated for use in reducing time to hemostasis and time to ambulation in patients who have undergone diagnostic procedures using 5, 6, or 8 French procedural sheaths. ## III. CONTRAINDICATIONS This product should not be used in patients who have a known sensitivity or allergy to porcine derived material or resorbable sutures. ## IV. WARNINGS AND PRECAUTIONS The warnings and precautions for the FISH™ device can be found in the Instructions for Use. ## V. DEVICE DESCRIPTION FISH™ is an approach to vascular closure that utilizes a patch of ExtraCellular Matrix (ECM), pre-mounted on a sheath introducer, to serve as the closure mechanism. The device is supplied in a sterile ready to use kit with access needle, guide wire and pre-dilator. The kit is packaged in a thermoform tray with a Tyvek™ covered lid. P050043 SSED Page 1 of 15 {1} # Materials and Configuration Small Intestinal Submucosa (SIS) Composition is a natural biomaterial, primarily composed of protein with secondary amounts of carbohydrates and lipids. SIS is obtained from porcine intestine using a process that retains the natural composition of matrix molecules such as collagen (Types I, III, VI), glycosaminoglycans (hyaluronic acid, chondroitin sulfate A and B, heparin, and heparin sulfate), proteoglycans, and glycoproteins (fibronectin), which are known to have important roles in host tissue repair and remodeling. ## VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative practices and procedures for attaining hemostasis at the femoral artery puncture site post-catheterization include mechanical compression, manual compression, percutaneous delivery of sutures at the femoral access site, collagen-based hemostasis devices and staples. ## VII. MARKETING HISTORY The FISH™ device has not been marketed within the United States or any place outside of the United States. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH The FISH™ System was evaluated in a randomized controlled clinical investigation involving 206 diagnostic patients enrolled at 8 United States clinical sites, 139 (67%) who received the FISH™ device and 67 (33%) the control, Manual Compression (MC). Prior to enrollment of randomized patients, each site enrolled non-randomized roll-in patients for training purposes. There were a total of 19 diagnostic roll-in patients. There was one (1) death reported during the randomized investigation, which was not device-related. This patient was randomized to the FISH™ device. Closure method-related adverse events seen in the clinical study were: - Hematoma - Bleeding Requiring Transfusion - Pseudoaneurysm Requiring Thrombin Injection Potential complications of allergic reaction, adhesion formation, infection or abscess, foreign body reaction, wound dehiscence, or vessel occlusion were not seen. Table 1 summarizes the adverse events reported within the randomized investigation’s 30-day follow-up period. Events are summarized by percentage of randomized patients experiencing the event during the clinical investigation. P050043 SSED Page 2 of 15 {2} Table 1. Major and Minor Complications through 30 Days – Diagnostic Intent-To-Treat (ITT) Patients | Cumulative Major and Minor Complications - Blackwelder Test for Equivalence | | | | | | | --- | --- | --- | --- | --- | --- | | Randomized Subjects n = 206 | FISH™ Device (n=139) | | Manual Comp. (n=67) | | p-value ** | | | % of Patients | No. of Events | % of Patients | No. of Events | | | | 95% CI * | | 95% CI * | Events | | | Combined Major Complications | 0.72% | 1 | 0% | 0 | <0.0001 | | | (0.02%, 3.94%) | | (0.0%, 5.36%) | | | | Access-site related bleeding requiring transfusion | 0.72% | 1 | 0 | 0 | <0.0001 | | | (0.01%, 2.88%) | | (0.0%, 3.42%) | | | | New ischemia in ipsilateral leg | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Vascular surgical repair, Ultrasound guided compression, transcatheter embolization, or stent graft | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Surgery for access-site related nerve injury | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Permanent access-site related nerve injury | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Access-site related infection requiring intravenous (IV) antibiotics and/or extended hospitalization | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Combined Minor Complications | 2.88% | 4 | 1.49% | 1 | 0.039 | | | (0.79%, 7.20%) | | (0.04%, 8.04%) | | | | Access-site related hematoma > 6cm | 2.16% | 3 | 1.49% | 1 | 0.012 | | | (0.45%, 6.18%) | | (0.04%, 8.04%) | | | | Pseudoaneurysm treated with ultrasound-guided thrombin injection | 0.72% | 1 | 0% | 0 | <0.0001 | | | (0.13%, 3.73%) | | (0.02%, 5.14%) | | | | Pseudoaneurysm treated with ultrasound-guided fibrin adhesive injection | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Non-treated pseudoaneurysm (documented by ultrasound) | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Non-treated Arteriovenous Fistula (documented by ultrasound) | 0 | 0 | 0 | 0 | -- | | | (0.0%, --) | | (0.0%, --) | | | | Device Success*** | 99% | -- | -- | -- | -- | | | 137/139 | | -- | | | | Procedure Success*** | 100% | -- | 100% | -- | -- | | | 139/139 | | 67/67 | | | * Exact 95% Confidence Interval (CI) based on Clopper-Pearson method ** Blackwelder's test with an equivalent limit of 0.05. The significance level of 0.041 was used for the interim analysis (p-value was not calculated if Adverse Event rates were 0 for both treatment groups) ***Device Success – the ability to achieve hemostasis without major adverse events or the use of mechanical compression and within the allotted time (60 minutes). *** Procedure Success – the ability to establish hemostasis in a given subject within any time period using any method. Table 1 shows that the overall Major Adverse Clinical Event (MACE) rates were 0.72% and 0.0% for FISH™ device and control group, respectively. The overall Minor Adverse Events rates were 2.88% and 1.5% for the FISH™ device and control group, respectively. The p-values were used for both MACE and Minor Adverse Events < 0.0001 and <0.041 respectively. The results of this statistical analysis demonstrate that the FISH™ device is non-inferior to Manual Compression in terms of safety. P050043 SSED Page 3 of 15 {3} # IX. SUMMARY OF PRECLINICAL STUDIES ## Objectives The objectives of the preclinical studies were to test the biocompatibility, device functionality, sterilization, and shelf life of the device. ## Biocompatibility The FISH™ device was studied for compatibility with standards listed in International Organization for Standardization (ISO) 10993 Biological Evaluation of Medical Devices. The evaluation included cytotoxicity, systemic toxicity, hemolysis, sensitization, irritation and pyrogenicity. The evaluation demonstrated that the FISH™ device is non-toxic, non-hemolytic, non-irritant, and non-pyrogenic. Table 2. Biocompatibility Test Results | Test Description | Standard Method | Category | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Cytotoxicity Study Using the ISO Elution Method, (1X Minimal Essential Media Extract) | ISO 10993-5 | 1 | No evidence of test sample causing cell lysis or toxicity. | PASS | | Murine Local Lymph Node Assay – 0.9% Sodium Chloride Extract | ISO 10993-10 | 1 | The test samples are to be considered not sensitizing to the animal. | PASS | | Murine Local Lymph Node Assay – Dimethyl Sulfoxide (DMSO) Extract | ISO 10993-10 | 1 | The test samples are to be considered not sensitizing to the animal. | PASS | | ISO Intracutaneous Study – Extract – Sesame Oil Extract | ISO 10993-10 | 1 | No evidence of irritation from the extract injected intracutaneously into rabbits. | PASS | | USP (United States Pharmacopeia) and ISO Systemic Toxicity Study – Extract – 0.9% Sodium Chloride Extract | ISO 10993-11 | 1 | No mortality or evidence of systemic toxicity from the extract injected into mice by either an intravenous or intraperitoneal route. | PASS | | USP and ISO Systemic Toxicity Study – Extract – Sodium Chloride Extract | ISO 10993-11 | 1 | No mortality or evidence of systemic toxicity from the extract injected into mice by either an intravenous or intraperitoneal route. | PASS | | In Vitro Hemolysis Study (Modified ASTM (American Society for Testing and Materials) Method) – 0.9% Sodium Chloride Extract | ISO 10993-4 | 1 | The test samples shall be found to be nonhemolytic. | PASS | P050043 SSED Page 4 of 15 {4} | Test Description | Standard Method | Category | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Plasma Recalcification Time Coagulation Study – Plasma Extract | ISO 10993-4 | 1 | The test samples shall not significantly decrease the coagulation time of human plasma. | PASS | | ISO Intracutaneous Study – Extract – 0.9% Sodium Chloride Extract | ISO 10993-10 | 1 | No evidence of irritation from the extract injected intracutaneously into rabbits. | PASS | | Thromboresistance | ISO 10993 | 2 | Cannot cause abnormal or significant thrombus | PASS | ## Functionality Laboratory testing was conducted on the FISH™ device to evaluate the physical characteristics of the device relative to its performance and safety. Results from these physical tests provide evidence that the device performs consistently and meets currently accepted industry standards. Table 3 summarizes the results of functionality device testing. Table 3. FISH™ Device Mechanical Testing | Test | Acceptance Criteria | Results | | --- | --- | --- | | Packaging (n=6) | | | | No Entrapment | No entrapment of suture, guidewire holder, guidewire | PASS | | No Breach | No breach of packaging | PASS | | No visible channels | No channel shall appear across the seal | PASS | | No lengthwise warp/curl | No lengthwise warp/curl greater than 0.25" | PASS | | Packaging Burst Test (n=6) | | | | Burst Pressure | No seal burst below 2.5 PSI (Pounds-force per Square Inch) | PASS | | Dilator Tip Insertion (n=9) | | | | Ease of Insertion | No visual sign of tip distortion | PASS | | Kinking of tubing | No dilator shall kink during insertion | PASS | | Sheath Tip Insertion (n=9) | | | | Ease of Insertion | No visual sign of tip distortion | PASS | | Kinking of tubing | No sheath shall kink during insertion | PASS | | SIS Sleeve Insertion (n=9) | | | | Ease of Insertion | All patches shall enter the in vitro model | PASS | | Note condition of SIS patch | No patch shall tear, suture break or sheath damage occur during insertion | PASS | | Remove Release Wire (n=9) | | | | Ease of removal | All release wires need to release without difficulty | PASS | | Advancement of Sheath (n=8) | | | | SIS patch resistance | Sheath shall move without moving patch | PASS | | Dilator Hub, Valve Cap Snap Fit (n=8) | | | | Ease of Removal | All dilator hubs must be removable from the sheath hubs | PASS | | Leak Test (n=8) | | | | Valve Cap | No leaks allowed | PASS | | Valve – Dilator | No leaks allowed | PASS | | Valve – Release Wire | No leaks allowed | PASS | P050043 SSED Page 5 of 15 {5} | Test | Acceptance Criteria | Results | | --- | --- | --- | | Handle | | | | Barb and Flush Tube | No leaks allowed | PASS | | Insertion Site | No leaks allowed | PASS | | Device Compatibility (n=8) | | | | Ease of Introduction | All devices must easily enter the hub and tubing of the sheath | PASS | | Resistance of advancing device | No device shall experience “hang up” or high resistance | PASS | | Leak Test – Hemostatic Valve (n=8) | | | | With catheter installed | No leaks shall develop with catheter in place in the sheath hub | PASS | | After catheter removed | No leaks shall develop when catheter is removed from sheath hub | PASS | | Device Compatibility (n=8) | | | | Removal of device | No device shall have difficulty being removed | PASS | | Removal of Sheath (n=8) | | | | Movement of SIS | SIS patch must stay in position and create a hydrostatic seal after sheath removal | PASS | | Centimeter markings (n=8) | | | | Adherence | At least 75% of marking shall remain after use | PASS | | Compression Mechanism (n=8) | | | | Pass/Fail | Compression suture shall deploy with minimal effort and not fail | PASS | | Release Wire Assembly (n=8) | | | | Retention Strength (lbs) | Assembly must equal or exceed 3.5lbs. | PASS | | Flushtube/Barb Assembly (n=9) | | | | Retention Strength (lbs) | Assembly must equal or exceed 4lbs. | PASS | | Suture Tab Assembly (n=6) | | | | Retention Strength (lbs) | Retention strength must exceed 2lbs or suture must break. | PASS | Various ISO and ASTM Standard were used in developing the protocols used in the test listed in the table above. ## Sterilization and Shelf Life The FISH™ device is packaged in a Tyvek™ covered polyethylene glycol (PEG) tray, which is heat sealed. All of the components are manufactured in a clean-room environment and the final product is sterilized using Ethylene Oxide (EtO) sterilization. The Sterilization process was validated with a modified Method “C” (Overkill Method) as referenced in Section B.4.3 of the International Standard document ANSI/AAMI/ISO 11135:1994. The successful execution of this demonstrated a theoretical $10^{-6}$ level of sterility or the probability of one non-sterile unit in one million. The product has passed 12 month shelf life testing included non-accelerated aging for both the device and packaging as well as meeting ASTM and ISO standards for drop testing, low pressure hazards, vehicle stacking and vehicle vibration. P050043 SSED Page 6 of 15 {6} Table 4. Results from sterilization testing | Acceptance Criteria | Results | | --- | --- | | Residue Testing: <20 mg/device for EtO | PASS | | Residue Testing: <12 ethylene chlorohydrin | PASS | | Product Sterility: Negative for growth for the half-cycle | PASS | | Bacteriostasis/Fungistasis: No evidence of bacteriostatic or fungistatic effects on product | PASS | | Biological Indicators - Internal Process Challenge Devices and External Process Challenge Devices: negative for growth | PASS | ## Animal Studies Animal testing was conducted to assess the safety and effectiveness of the FISH™ device. The animal testing was performed in 12 canines and 8 swine with one device per animal. Six animals were evaluated acutely (24 hours) and 14 were evaluated with chronic follow-up (2-50 days). The results provided preliminary evidence of device safety and effectiveness when the device is used as directed. ## X. SUMMARY OF CLINICAL STUDIES ### Objectives The objectives of the clinical studies were to assess the safety and effectiveness of the FISH™ device in the treatment of bleeding that occurs during femoral artery catheterization. ### Study Design The FISH™ closure device was studied in an open-label, randomized, multi-center clinical trial which enrolled 297 diagnostic and interventional patients. This United States based trial compared the FISH™ device to manual compression. The study included both diagnostic (N=206) and interventional (N=91) patients requiring a procedure with an 8 Fr or smaller sheath size. The study of interventional patients with the FISH™ device is currently ongoing. Data from the interventional study is not discussed here. Each investigator had the opportunity to enroll up to 2 roll-in patients which were non-randomized patients. There were a total of 28 roll-in (diagnostic and interventional) patients in the study. The patients were randomized using a 2:1 randomization scheme (FISH™ device vs. Manual Compression). Of the 206 diagnostic patients enrolled in the study, 139 received the FISH™ device and 67 received manual compression. This study included 8 U.S. sites and enrolled patients between January 2004 and June 2006. There were a total of 40 investigators who enrolled patients for the study. The endpoints for the study were safety where the study device was required to show equivalence to the control and effectiveness where the device was required to demonstrate superiority in reduced time hemostasis, ambulation, eligible discharge and discharge. P050043 SSED Page 7 of 15 {7} All patients enrolled in the study provided a signed written informed consent and agreed to return for a follow-up evaluation at $30 \pm 5$ days. The study included patients who were undergoing diagnostic or therapeutic coronary or peripheral procedure performed percutaneously via the common femoral artery. The candidates were required to meet general inclusion and exclusion criteria. The patients did not require a femoral artery angiogram prior to placement of the $\mathrm{FISH}^{\mathrm{TM}}$ device. ## Inclusion Criteria Patients were enrolled in the study if they met all of the following inclusion criteria: 1. Candidate for a diagnostic or therapeutic coronary or peripheral procedure performed percutaneously via the common femoral artery 2. Patient age > 18 years old and < 80 years old 3. Patient agrees to return for a follow-up evaluation at $30 \pm 5$ days 4. Patient provides a signed written informed consent ## Exclusion Criteria Patients were not enrolled in the study if any of the following exclusion criteria were present: 1. Known significant bleeding or platelet disorder 2. Von Willebrand’s disease 3. Anemia (Hgb (Hemoglobin) < 10 grams per deciliter, Hct (Hematocrit) < 30%) 4. Thrombasthenia 5. Systemic Hypertension (> 180 mm Hg systolic) unresponsive to treatment 6. Pregnant or lactating 7. ACT (Activated Clotting Time) > 400 seconds at time of sheath removal 8. A known allergic reaction to pork products or any other materials used in the device 9. Preexisting immune deficiency 10. Needing a procedure requiring an introducer sheath size of > 8 French 11. Arterial closure site depth > 7.5 centimeters 12. Ipsilateral arterial site closure with manual compression ≤ 6 weeks before the catheterization procedure 13. Closure with another closure device ≤ 180 days before the catheterization procedure. 14. Known hypercoagulable – repeated problems with clotting 15. Patient has unilateral or bilateral lower extremity amputation(s) 16. Patient is unable to routinely walk at least 20 feet without assistance 17. Patient has active systemic or cutaneous infection or inflammation 18. Patient has a pre-existing severe noncardiac systemic disease or illness that results in an expected life expectancy of < 30 days 19. Patient is participating in the study of another investigational device or drug in which follow-up is ongoing 20. Systemic fibrinolytic agents have been used ≤ 24 hours prior to or during the catheterization procedure such that the fibrinogen level is < 100 mg/dl (milligrams per deciliter) P050043 SSED Page 8 of 15 {8} 21. There is indication that puncture has been made in the profunda femoris artery, superficial femoral artery, or at the bifurcation of the arteries 22. Patient has had prior ipsilateral femoral vascular surgery or prior stent placement in the vicinity of the puncture site 23. The puncture site is through a vascular graft 24. There has been use of an intra-aortic balloon pump through the arterial puncture site. 25. Patient has an ipsilateral venous sheath 26. Pseudoaneurysm, arteriovenous (AV) fistula, intraluminal thrombus, or arterial dissection are present in the ipsilateral femoral artery prior to arterial closure 27. Patient has intra-procedural bleeding around the access site 28. Patient has a palpable ipsilateral hematoma of any size observed during the catheterization procedure 29. Patient develops absent pedal pulses in the ipsilateral lower extremity during the catheterization procedure 30. Systolic blood pressure is < 90 mm Hg after the catheterization procedure and before device deployment 31. There was difficulty attaining arterial access, multiple punctures were required for arterial access, or the posterior wall of the femoral artery was thought to have been punctured during arterial access 32. There was difficulty inserting the introducer sheath at the start of the catheterization procedure due to vessel scarring or tortuosity 33. Patient is determined to require a procedure that will extend his/her hospitalization (e.g., patient is undergoing Coronary Artery Bypass Graft (CABG) surgery) 34. Patient has already participated in this study ## Effectiveness Endpoints The study was designed to demonstrate that time to hemostasis (TTH) is superior as compared to the control therapy. TTH was measured from the time of sheath pull to the time the patient achieved hemostasis. For this study, the time of hemostasis was defined as “absence of oozing blood that is readily treated by light compression methods (e.g., sandbags, pressure dressing, light manual pressure).” The study was also designed to demonstrate time to ambulation (TTA) as superior compared to the control therapy. TTA was measured from the time of sheath removal to the time when the patient stood at the bedside and walked at least 20 feet without evidence of re-bleeding. Secondary endpoints included the measure of time to eligible discharge (TTED), time to discharge (TTD), procedure success rate, and patient discomfort. ## Safety Endpoints The null hypothesis for safety was that the experimental device had a major adverse event rate that exceeded that of the control by a delta of 5%. The alternative hypothesis was that the experimental device has a primary safety endpoint rate less than that of the control or exceeding that of the control by no more than the delta 5%. P050043 SSED Page 9 of 15 {9} Null Hypothesis $$ \text{FISH}^{\text{TM}} (\%\text{MACE}) > \text{Manual Compression} (\%\text{MACE}) + 5\% \text{ delta} $$ Alternative Hypothesis $$ \text{FISH}^{\text{TM}} (\%\text{MACE}) < \text{Manual Compression} (\%\text{MACE}) + 5\% \text{ delta} $$ ## Patient Assessments All patients were required to return for a follow-up examination at $30 \pm 5$ days. All adverse events were recorded and physical examinations of the sites were conducted. In addition, 150 patients received femoral ultrasound evaluations of the puncture site for evidence of vascular compromise, arterio-venous fistulae or pseudoaneurysms; at 30 days, no significant findings were identified. ## Demographics The average patient age was 60 years, the average activated clotting time (ACT) at the time of sheath pull was 129 seconds and $62\%$ of the patients were diagnosed with hypertension. ## Effectiveness Results For all effectiveness endpoints the FISH™ device proved superior in diagnostic patients compared to the control manual compression. The median times for hemostasis in the FISH™ patients were 6 minutes versus 17 minutes for the control group manual compression. The median times for ambulation for the FISH™ device were 2.0 hours for the FISH™ group versus 4.2 hours for the control. The median time to eligible discharge was 2.3 hours versus 4.5 hours for the control manual compression. The median time to discharge was 3.0 hours for the FISH™ patients versus 4.9 hours for the control group manual compression. ![img-0.jpeg](img-0.jpeg) Figure 1. Histogram of Percentage of Patients vs. Time to Hemostasis (in minutes) P050043 SSED Page 10 of 15 {10} ![img-1.jpeg](img-1.jpeg) Figure 2. Histogram of Percentage of Patients vs. Time to Ambulation (in minutes) Table 5. Diagnostic Procedures: Effectiveness Endpoint Results for ITT Patients* | Primary Effectiveness | | | | | --- | --- | --- | --- | | Time to Hemostasis (Minutes) | FISH™ | Manual Compression | p-value | | N* | 139 | 67 | <0.0001 | | Mean (Standard Deviation) | 9.4 (8.7) | 17.2 (6.7) | | | Median | 6 | 17 | | | Min – Max | 2 - 75 | 7 – 55 | | | Time to Ambulation (Hours) | FISH™ | Manual Compression | p-value | | N* | 131 | 65 | <0.0001 | | Mean (Standard Deviation) | 2.6 (2.5) | 4.3 (1.0) | | | Median | 2.0 | 4.2 | | | Min – Max | 0.9 – 19.6 | 1.3 – 7.3 | | | Secondary Effectiveness | | | | | Time to Eligible Discharge (Hours) | FISH™ | Manual Compression | p-value | | N* | 130 | 65 | <0.0001 | | Mean (Standard Deviation) | 3.1 (3.3) | 5.5 (4.0) | | | Median | 2.3 | 4.5 | | | Min – Max | 1 – 22.4 | 1.5 - 24.2 | | | Time to Discharge (Hours) | FISH™ | Manual Compression | p-value | | N* | 127 | 65 | <0.0001 | | Mean (Standard Deviation) | 16.2 (43.1) | 24.9 (53.1) | | | Median | 3.0 | 4.9 | | | Min – Max | 1.5 - 263 | 3.4 – 217.9 | | | Equivalence Study At 30 Days | | | | | Discomfort (Subjective Scale 0-10) | FISH™ | Manual Compression | p-value | | N* | 138 | 67 | -- | | Mean (Standard Deviation) | 0.51 (1.5) | 0.21 (1.0) | | | Median | 0 | 0 | | | Min – Max | 0 - 8 | 0 – 6 | | *The effectiveness calculations were based on the Wilcoxon Two-Sample Test using a normal approximation and two-sided criteria (Pr > Z < .0001). *Note: Differences in sample sizes between variables were due to missing data points or delays due to subsequent procedures. P050043 SSED Page 11 of 15 {11} The results of the above statistical analyses demonstrate that the FISH™ device is superior to Manual Compression in terms of effectiveness measures for vascular hemostasis and equivalent relative to discomfort subjectively measured at 30 days post-procedure. Table 6. Diagnostic Procedures: Patient Distribution for TTH, TTA, TTED, TTD | Variable | FISH™ | Control Manual Compression | | --- | --- | --- | | Time to Hemostasis | | | | ≤ 6min | 50.72% (70/138)* | 0.00% (0/67) | | ≤ 12min | 83.33% (115/138) | 22.39% (15/67) | | ≤ 18min | 89.86% (124/138) | 52.24% (35/67) | | ≤ 24min | 97.10% (134/138) | 92.54% (62/67) | | ≤ 30min | 97.83% (135/138) | 98.51% (66/67) | | Time to Ambulation | | | | ≤ 2 hours | 50.77% (66/130)* | 1.54% (1/65) | | ≤ 3 hours | 79.23% (103/130) | 6.15% (4/65) | | ≤ 5 hours | 96.15% (125/130) | 83.08% (54/65) | | ≤ 7 hours | 97.69% (127/130) | 96.92% (63/65) | | ≤ 10 hours | 98.46% (128/130) | 100.00% (65/65) | | Time to Eligible Discharge | | | | ≤ 2 hours | 41.86% (54/129)* | 1.54% (1/65) | | ≤ 3 hours | 72.87% (94/129) | 3.08% (2/65) | | ≤ 5 hours | 91.47% (118/129) | 72.31% (47/65) | | ≤ 7 hours | 96.12% (124/129) | 92.31% (60/65) | | ≤ 10 hours | 97.67% (126/129) | 93.85% (61/65) | | Time to Discharge | | | | ≤ 2 hours | 15.08% (19/126)* | 0.00% (0/65) | | ≤ 3 hours | 50.00% (63/126) | 0.00% (0/65) | | ≤ 5 hours | 76.98% (97/126) | 58.46% (38/65) | | ≤ 10 hours | 82.54% (104/126) | 80.00% (52/65) | | ≤ 24 hours | 88.10% (111/126) | 86.15% (56/65) | | ≤ 48 hours | 92.86% (117/126) | 87.69% (57/65) | *Note: Differences in total number of patients between variables were due to missing data points or delays due to subsequent procedures. ## Secondary Effectiveness Endpoints - Time to Eligible Discharge (TTED) – this was measured from the time of sheath pull to the time when the patient was deemed eligible for discharge from the hospital based only on the condition of the access site. The study demonstrated TTED superiority of the FISH™ device as compared to the control therapy. P050043 SSED Page 12 of 15 {12} ![img-2.jpeg](img-2.jpeg) Figure 3. Histogram of Percentage of Patients vs. Time to Eligible Discharge (in minutes) - Time to Discharge (TTD) – this was measured from time of sheath removal to the time the patient was discharged. The study demonstrated TTD superiority of the FISH™ device as compared to the control therapy. ![img-3.jpeg](img-3.jpeg) Figure 4. Histogram of Percentage of Patients vs. Time to Discharge (in minutes) - Patient Discomfort – All patients were subjectively asked at the 30 day follow-up to rate their site-related discomfort from 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. The results from this subjective study showed the device to be equal to the control. ![img-4.jpeg](img-4.jpeg) Figure 5. Average and Standard Deviation of Patients Discomfort at 30 Days (Subjective Scale 0-10) P050043 SSED Page 13 of 15 {13} - Procedure Success Rate (defined as the number of patients in which hemostasis was achieved with freedom from major complications vs. the number attempted). This includes hemostasis which was achieved using adjunctive compression (such adjunctive compression is typically used for ≤ 5 minutes). ## Device Failures Device failure was defined as an instance in which hemostasis could not be achieved using the FISH™ device within an allotted time (60 minutes) or with Manual Compression (Control), meaning when additional means such as a fem-stop or a mechanical compression clamp were required to achieve hemostasis. Only one case of device failure was noted in the diagnostic patients. ## Gender Differences According to one study, approximately 36% of patients receiving catheterization are female. Of the study population for this trial, 38% of the patient population were female. There was one report of a major adverse event (n=1) in the treatment group which was of a female patient. There were four total reports of combined major and minor adverse events. Three of these events occurred in women. Other endpoints did not show a statistically significant difference. Differences in the time to discharge endpoints are shown below. Table 7. Time to discharge – gender differences | Procedure | Randomization | Gender | Ave TTH | Ave TTA | Ave TTED | Ave TTD | | --- | --- | --- | --- | --- | --- | --- | | Diagnostic | Manual Compression | Female | 17.06 | 251.2 | 356.1 | 1231.2 | | | | Male | 17.4 | 268.8 | 302.8 | 1786.6 | | | | p-value | 0.828 | 0.263 | 0.371 | 0.487 | | | Device FISH™ | Female | 8.12 | 123.0 | 158 | 310.9 | | | | Male | 9.4 | 162.3 | 195.5 | 1252.2 | | | | p-value | 0.288 | 0.085 | 0.267 | 0.029 | Time to Discharge (TTD) was one effectiveness category that showed a statistically significant correlation with patient gender. This endpoint was often controlled by other parameters outside the influence of the type of closure method. This included patients who were going to have subsequent procedures based on the diagnostic procedure performed. These subsequent procedures could add significantly to the average TTD even if only a small subgroup of patients went on to follow-up procedures as seen in the chart. ## Safety Results For the diagnostic patients, the FISH™ device demonstrated safety with a total adverse event rate of 0.7% (1/139) versus the control 0.0% (0/67). The one event for the FISH™ device was a site-related bleeding requiring transfusion. These rates for MACE in the diagnostic patients were found to be equivalent (p < 0.0001) under the experimental conditions outlined prospectively in the investigational plan. P050043 SSED Page 14 of 15 {14} The minor adverse event rate was low for both the FISH™ device (2.9%) and the control (1.5%); the tests for equivalence showed these to be equal (p=0.039). The events for the device include 3 hematomas > 6 cm and 1 pseudoaneurysm. For the control there was one hematoma > 6 cm. During the course of this clinical trial there was one patient death (1 FISH™, 0 Manual Compression). The death was not related to the use of the device. There were no Unanticipated Site-Related Adverse Events. Please see Table 1 for major and minor complications through 30 days. ## XI. CONCLUSIONS DRAWN FROM STUDIES Based on the results from the clinical, *in vivo* and *in vitro* studies there is valid scientific evidence and reasonable assurance that the FISH™ device is safe and effective when used in accordance with the instructions for use. The FISH™ device has demonstrated safety through its low incidence of complications in diagnostic patients when compared to manual compression. The FISH™ device has demonstrated effectiveness by achieving hemostasis and ambulation earlier than the control group using manual compression. ## XII. 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 Support Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel. ## XIII. CDRH DECISION FDA issued an approval order on August 20, 2007. The applicant's manufacturing facility was inspected and was found to be in compliance with the Quality System Regulation (21 CFR 820). ## XIV. APPROVAL SPECIFICATIONS Directions for use: See the labeling. Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions and Adverse Events in the labeling. Postapproval Requirements and Restrictions: See approval order. ## XV. REFERENCES 1. Saif S. Rathore, MPH; Yongfei Wang, MS; Martha J. Radford, MD; Diana L. Ordin, MD, MPH; and Harlan M. Krumholz, MD, SM. Sex Differences in Cardiac Catheterization after Acute Myocardial Infarction: The Role of Procedure Appropriateness. Volume 137, Issue 6; pp. 487-493:2002. P050043 SSED Page 15 of 15 --- **Source:** [https://fda.innolitics.com/device/P050043](https://fda.innolitics.com/device/P050043) **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