Fibrin Sealant Vascular Surgery Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/ml thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) for hemostasis in participants receiving prosthetic expanded polytetrafluoroethylene (ePTFE) conduits as compared to a control group treated by manual compression with surgical gauze pads.

Official Title
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Clinical Evaluation of Efficacy and Safety of FS VH S/D 500 S-apr for Hemostasis in Subjects Undergoing Vascular Surgery

Conditions
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Adjunct to Hemostasis in Vascular Surgery (Synthetic Vascular Grafts)

Intervention / Treatment
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* Biological: FS VH S/D 500 s-apr, 60-seconds polymerization time
* Biological: FS VH S/D 500 s-apr, 120-seconds polymerization time
* Procedure: Manual compression with surgical gauze pads


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of all ages Subject undergoing peripheral vascular surgery, ie, conduit placement with an ePTFE graft such as arterio-arterial bypasses [including: axillo-femoral, ilio-femoral, femoro-femoral, ilio-popliteal, femoro-popliteal (including below knee), femoro-tibial vessel bypass], or arteriovenous dialysis access shunt in the upper or lower extremity. Signed informed consent Intraoperative inclusion criterion: - Suture line bleeding eligible for study treatment is present after surgical hemostasis (i.e., suturing). Suture line bleeding eligible for study treatment is defined as: any suture line bleeding that would prevent immediate closure of the wound and require treatment of the bleeding first, and on a scale of mild, moderate, and severe, the suture line bleeding is assessed as moderate or severe. (Moderate is defined as: either more than 25% of the suture line bleeds, or at least 5 suture line bleedings are present, if counting of suture line bleedings is possible, or one pulsatile suture line bleeding is present. Severe is defined as: either more than 50% of the suture line bleeds, or at least 10 suture line bleedings present, if counting of suture line bleedings is possible, or more than one pulsatile suture line bleedings are present, or at least one spurting suture line bleeding is present.) Note: Bleedings that can be treated with additional sutures are not appropriate for the study. Such anastomoses should receive additional sutures, be re-categorized, and if they still comply with the inclusion criteria, be randomized. Exclusion Criteria: Subjects concurrently participating in another clinical study treatment with another investigational drug or device within the last 30 days Other vascular procedures during the same surgical session (stenting and/or endarterectomy of the same artery are allowed) Arterio-arterial bypasses with more than 2 anastomoses (e.g., aorto-bifemoral, axillo-bifemoral etc.) Pregnant or lactating women Congenital coagulation disorders Prior kidney transplantation Heparin-induced thrombocytopenia Known prior exposure to aprotinin within the last 12 months Known hypersensitivity to aprotinin or other components of the product Known severe congenital or acquired immunodeficiency (e.g., HIV infection or long term treatment with immunosuppressive drugs) Prior radiation therapy to the operating field Severe local inflammation at the operating field. Intraoperative exclusion criterion: Major intraoperative complications that require resuscitation or deviation from the planned surgical procedure. Intraoperative change in planned surgical procedure, which results in subject no longer meeting preoperative inclusion and/or exclusion criteria, (e.g. abandonment of ePTFE graft placement).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FS VH S/D 500 s-apr - 60-Seconds<br>Fibrin Sealant, Vapor Heated, Solvent/Detergent-treated with 500 IU/ml thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) will be applied to the study suture line, 60-second polymerization time | Biological: FS VH S/D 500 s-apr, 60-seconds polymerization time<br>* FS VH S/D 500 s-apr (FS) is applied to the study suture line. The actual dose of FS VH S/D 500 s-apr depends on the length of the suture line and the intensity of bleeding and is to be decided by the surgeon, but the maximum dose per suture line shall not exceed 4 mL FS VH S/D 500 s apr. After application of FS VH S/D 500 s-apr to the study suture line is completed, the surgeon will wait for 1 minute to allow polymerization of FS VH S/D 500 s-apr.<br>|
| Experimental: FS VH S/D 500 s-apr - 120-Seconds<br>FS VH S/D 500 s-apr will be applied to the study suture line, 120-second polymerization time | Biological: FS VH S/D 500 s-apr, 120-seconds polymerization time<br>* Treatment will be identical to the FS VH S/D 500 s-apr Group, 60 seconds polymerization time, except that the surgeons will wait 2 minutes to allow polymerization and will then open the cross clamps.<br>|
| Active Comparator: Control Group- Manual compression with surgical gauze pads<br>Treatment of the study-suture line will be manual compression with surgical gauze pads. | Procedure: Manual compression with surgical gauze pads<br>* Treatment of the study suture line with manual compression with surgical gauze pads.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hemostasis at 4 Minutes After Treatment Application at the Study Suture Line. | Hemostasis at the study suture line must be maintained. Participants were considered treatment failures if they met any of the following conditions: Did not achieve hemostasis at 4 minutes Required additional hemostatic treatment during the first 4 minutes of the observation period Experienced rebleeding after the first 4 minutes of the observation period. | 4 minutes post start of treatment application | 
| 90% Confidence Interval for the Percentage of Participants Achieving Hemostasis at 4 Minutes After Treatment Application at the Suture Line | Hemostasis at the study suture line must be maintained until closure of the surgical wound. Participants were considered treatment failures if they met any of the following conditions: Did not achieve hemostasis at 4 minutes Required additional hemostatic treatment other than study treatment during the first 4 minutes of the observation period Experienced rebleeding after the first 4 minutes of the observation period. | 4 minutes post start of treatment application | 
| Hemostasis at 4 Minutes After Treatment Application at the Suture Line by Bleeding Severity - Moderate Bleeding | Investigators were shown videos of bleeding severities to standardize assessments. Moderate bleeding defined as: Either >25% of the suture line bleeds, or ≥5 suture line bleedings were present, if counting of suture line bleedings was possible, or 1 pulsatile suture line bleeding was present. Severe bleeding defined as: Either >50% of the suture line bleeds, or ≥10 suture line bleedings were present, if counting of suture line bleedings was possible, or >1 pulsatile suture line bleeding was present, or ≥1 spurting suture line bleeding was present. | 4 minutes post start of treatment application | 
| Hemostasis at 4 Minutes After Treatment Application at the Suture Line by Bleeding Severity - Severe Bleeding | Investigators were shown videos of bleeding severities to standardize assessments. Severe bleeding defined as: Either >50% of the suture line bleeds, or ≥10 suture line bleedings were present, if counting of suture line bleedings was possible, or >1 pulsatile suture line bleeding was present, or ≥1 spurting suture line bleeding was present. | 4 minutes post start of treatment application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hemostasis at 6 Minutes | Hemostasis at the study suture line must be maintained until closure of the surgical wound. | 6 minutes post start of treatment application start | 
| Percentage of Participants Achieving Hemostasis at 10 Minutes | Hemostasis at the study suture line must be maintained until closure of the surgical wound. | 10 minutes post start of treatment application | 
| Percentage of Participants With Intraoperative Rebleeding After Hemostasis at the Study Suture Line | Intraoperative rebleeding at the study suture line after occurrence of hemostasis. | Intraoperative day 0 | 
| Percentage of Participants With Postoperative Rebleeding After Hemostasis at the Study Suture Line | Any rebleeding requiring surgical reexploration | Postoperative through day 30 ± 5 | 
| Percentage of Participants With Any Transfusion Requirement | Proportion of participants who required transfusions (i.e., red blood cell (RBC) concentrates, fresh frozen plasma (FFP), and platelets) | Intraoperative (day 0) through day 30 ± 5 | 
| Percentage of Participants With Graft Occlusions | Determined clinically and defined as absence of blood flow through the graft. | Day 0 (procedure day) through day 30 ± 5 | 
| Percentage of Participants With Infections at the Surgical Site |  | Day 0 (procedure day) through day 30 ± 5 | 
| Vital Signs: Systolic and Diastolic Blood Pressure - Preoperative Baseline |  | Within 14 days prior to date of surgery | 
| Percent Change in Vital Signs: Systolic and Diastolic Blood Pressure | Percent Change in Systolic and Diastolic Blood Pressure (BP) Measured as: Preoperative Baseline - Intraoperative Day 0; Preoperative Baseline - Postoperative Day 1; and Preoperative Baseline - Postoperative Day 14 | Preoperative baseline through postoperative Day 14 | 
| Vital Signs: Heart Rate - Preoperative Baseline |  | Within 14 days prior to date of surgery | 
| Percent Change in Vital Signs: Heart Rate | Percent Change in Heart Rate Measured as: Preoperative Baseline - Intraoperative Day 0; Preoperative Baseline - Postoperative Day 1; and Preoperative Baseline - Postoperative Day 14 | Preoperative baseline through postoperative Day 14 | 
| Vital Signs: Respiratory Rate - Preoperative Baseline |  | Within 14 days prior to date of surgery | 
| Percent Change in Vital Signs: Respiratory Rate | Percent Change in Respiratory Rate Measured as: Preoperative Baseline - Intraoperative Day 0; Preoperative Baseline - Postoperative Day 1; and Preoperative Baseline - Postoperative Day 14 | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Hemoglobin |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Hematocrit |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Erythrocytes |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Leukocytes, Basophils, Eosinophils, Lymphocytes, Neutrophils, and Monocytes |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Platelets |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Creatinine, Bilirubin, and Blood Urea Nitrogen (BUN) |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Alanine Aminotransferase (ALT) |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Aspartate Aminotransferase (AST) |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: Activated Partial Thromboplastin Time (aPTT) |  | Preoperative baseline through postoperative Day 14 | 
| Laboratory Values Over Time: International Normalized Ratio (INR) |  | Preoperative baseline through postoperative Day 14 |