Fibrin Sealant Vascular Surgery Study - Full Text View

Purpose

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.

Condition	Intervention	Phase
Adjunct to Hemostasis in Vascular Surgery (Synthetic Vascular Grafts)	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	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Clinical Evaluation of Efficacy and Safety of FS VH S/D 500 S-apr for Hemostasis in Subjects Undergoing Vascular Surgery

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:

Percentage of Participants Achieving Hemostasis at 4 Minutes After Treatment Application at the Study Suture Line. [ Time Frame: 4 minutes post start of treatment application ] [ Designated as safety issue: No ]
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.
90% Confidence Interval for the Percentage of Participants Achieving Hemostasis at 4 Minutes After Treatment Application at the Suture Line [ Time Frame: 4 minutes post start of treatment application ] [ Designated as safety issue: No ]
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.
Hemostasis at 4 Minutes After Treatment Application at the Suture Line by Bleeding Severity - Moderate Bleeding [ Time Frame: 4 minutes post start of treatment application ] [ Designated as safety issue: No ]
Investigators were shown videos of bleeding severities to standardize assessments.
1. 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.
2. 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.
Hemostasis at 4 Minutes After Treatment Application at the Suture Line by Bleeding Severity - Severe Bleeding [ Time Frame: 4 minutes post start of treatment application ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Percentage of Participants Achieving Hemostasis at 6 Minutes [ Time Frame: 6 minutes post start of treatment application start ] [ Designated as safety issue: No ]
Hemostasis at the study suture line must be maintained until closure of the surgical wound.
Percentage of Participants Achieving Hemostasis at 10 Minutes [ Time Frame: 10 minutes post start of treatment application ] [ Designated as safety issue: No ]
Hemostasis at the study suture line must be maintained until closure of the surgical wound.
Percentage of Participants With Intraoperative Rebleeding After Hemostasis at the Study Suture Line [ Time Frame: Intraoperative day 0 ] [ Designated as safety issue: No ]
Intraoperative rebleeding at the study suture line after occurrence of hemostasis.
Percentage of Participants With Postoperative Rebleeding After Hemostasis at the Study Suture Line [ Time Frame: Postoperative through day 30 ± 5 ] [ Designated as safety issue: No ]
Any rebleeding requiring surgical reexploration
Percentage of Participants With Any Transfusion Requirement [ Time Frame: Intraoperative (day 0) through day 30 ± 5 ] [ Designated as safety issue: No ]
Proportion of participants who required transfusions (i.e., red blood cell (RBC) concentrates, fresh frozen plasma (FFP), and platelets)
Percentage of Participants With Graft Occlusions [ Time Frame: Day 0 (procedure day) through day 30 ± 5 ] [ Designated as safety issue: Yes ]
Determined clinically and defined as absence of blood flow through the graft.
Percentage of Participants With Infections at the Surgical Site [ Time Frame: Day 0 (procedure day) through day 30 ± 5 ] [ Designated as safety issue: Yes ]
Vital Signs: Systolic and Diastolic Blood Pressure - Preoperative Baseline [ Time Frame: Within 14 days prior to date of surgery ] [ Designated as safety issue: Yes ]
Percent Change in Vital Signs: Systolic and Diastolic Blood Pressure [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
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
Vital Signs: Heart Rate - Preoperative Baseline [ Time Frame: Within 14 days prior to date of surgery ] [ Designated as safety issue: Yes ]
Percent Change in Vital Signs: Heart Rate [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Percent Change in Heart Rate Measured as: Preoperative Baseline - Intraoperative Day 0; Preoperative Baseline - Postoperative Day 1; and Preoperative Baseline - Postoperative Day 14
Vital Signs: Respiratory Rate - Preoperative Baseline [ Time Frame: Within 14 days prior to date of surgery ] [ Designated as safety issue: Yes ]
Percent Change in Vital Signs: Respiratory Rate [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Percent Change in Respiratory Rate Measured as: Preoperative Baseline - Intraoperative Day 0; Preoperative Baseline - Postoperative Day 1; and Preoperative Baseline - Postoperative Day 14
Laboratory Values Over Time: Hemoglobin [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Hematocrit [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Erythrocytes [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Leukocytes, Basophils, Eosinophils, Lymphocytes, Neutrophils, and Monocytes [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Platelets [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Creatinine, Bilirubin, and Blood Urea Nitrogen (BUN) [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Alanine Aminotransferase (ALT) [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Aspartate Aminotransferase (AST) [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]
Laboratory Values Over Time: International Normalized Ratio (INR) [ Time Frame: Preoperative baseline through postoperative Day 14 ] [ Designated as safety issue: Yes ]

Enrollment:	101
Study Start Date:	December 2007
Study Completion Date:	December 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: FS VH S/D 500 s-apr - 60-Seconds 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 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.
Experimental: FS VH S/D 500 s-apr - 120-Seconds 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 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.
Active Comparator: Control Group- Manual compression with surgical gauze pads Treatment of the study-suture line will be manual compression with surgical gauze pads.	Procedure: Manual compression with surgical gauze pads Treatment of the study suture line with manual compression with surgical gauze pads.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576420

Locations

United States, Alabama

Birmingham, Alabama, United States
United States, Arizona

Tucson, Arizona, United States
United States, California

Long Beach, California, United States
United States, Florida

Jacksonville, Florida, United States
United States, Kentucky

Lexington, Kentucky, United States
United States, Louisiana

Baton Rouge, Louisiana, United States
United States, Pennsylvania

Pittsburgh, Pennsylvania, United States
United States, Utah

Salt Lake City, Utah, United States
United States, Virginia

Charlottesville, Virginia, United States

Virginia Beach, Virginia, United States
United States, Washington

Seattle, Washington, United States

Sponsors and Collaborators

Baxter Healthcare Corporation

More Information

Publications:

Saha SP, Muluk S, Schenk W 3rd, Burks SG, Grigorian A, Ploder B, Presch I, Pavlova BG, Hantak E. Use of fibrin sealant as a hemostatic agent in expanded polytetrafluoroethylene graft placement surgery. Ann Vasc Surg. 2011 Aug;25(6):813-22. Epub 2011 Apr 21.

Responsible Party:	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00576420 History of Changes
Other Study ID Numbers:	550602
Study First Received:	December 18, 2007
Results First Received:	September 13, 2012
Last Updated:	October 26, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Fibrin Tissue Adhesive
Hemostatics
Coagulants

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013