The EVARREST® Fibrin Sealant Patch Liver Study

A Phase III Randomized, Controlled, Superiority Study Evaluating EVARREST® Fibrin Sealant Patch Versus Standard of Care Treatment in Controlling Parenchymal Bleeding During Hepatic Surgery

To evaluate the safety and hemostatic effectiveness of EVARREST® Fibrin Sealant Patch (EVARREST) versus standard of care treatment (SoC) in controlling parenchymal bleeding during hepatic surgery.

Study Overview

• Status: Completed
• Conditions: Hemorrhage
• Intervention / Treatment: Other: Standard of Care (SoC); Biological: EVARREST® Fibrin Sealant Patch

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • Clinical Investigation Site #3
  • Woodville South, Australia, 5011
    • Clinical Investigation Site #2
• New Zealand
  • Auckland, New Zealand, 93-503
    • Clinical Investigation Site #1
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Clinical Investigation Site #6
  • Cambridge, United Kingdom, CB2 0QQ
    • Clinical Investigation Site #7
  • Edinburgh, United Kingdom, EH16 4SA
    • Clinical Investigation Site #4
  • Leeds, United Kingdom, LS9 7TF
    • Clinical Investigation Site #5
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Clinical Investigation Site #13
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Clinical Investigation Site #10
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Clinical Investigation Site #16
    • Chicago, Illinois, United States, 60637
      • Clinical Investigation Site #12
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Clinical Investigation Site #15
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Clinical Investigation Site #9
  • New York
    • New York, New York, United States, 10032
      • Clinical Investigation Site #11
    • New York, New York, United States, 10065
      • Clinical Investigation Site #14
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Clinical Investigation Site #8
    • Pittsburgh, Pennsylvania, United States, 15213
      • Clinical Investigation Site #17

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects ≥ 18 years of age, requiring elective or urgent, open hepatic surgery.
• Presence of an appropriate bleeding hepatic parenchymal Target Bleeding Site (TBS) as identified intra-operatively by the surgeon
• Subjects or legally authorized representatives must be willing to participate in the study, and provide written informed consent. (Note: This criteria does allow for hospital translators to be used where approved by Ethics Committees/Institutional Review Boards)

Exclusion Criteria:

• Subjects with any intra-operative findings identified by the surgeon that may preclude conduct of the study procedure;
• TBS is from large defects in arteries or veins where the injured vascular wall requires repair with maintenance of vessel patency and which would result in persistent exposure of EVARREST® to blood flow and pressure during healing and absorption of the product;
• TBS with major arterial bleeding requiring suture or mechanical ligation;
• Subjects admitted for trauma surgery;
• Subject is a transplant patient for fulminant hepatic failure
• Subject with TBS within an actively infected field;
• Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony confine;
• Subjects with known intolerance to blood products or to one of the components of the study product or is unwilling to receive blood products;
• Subjects who are known, current alcohol and / or drug abusers;
• Subjects who have participated in another investigational medical device or investigational drug trial within 30 days of surgery or are expected to participate in another medical device or investigational drug trial during the course of the study;
• Female subjects who are pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EVARREST® Fibrin Sealant Patch; EVARREST® Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts - a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin).	Biological: EVARREST® Fibrin Sealant Patch
OTHER: Standard of Care (SoC); SoC is a composite of techniques/methods typically used by the surgeon to control bleeding after conventional methods (i.e. suture, ligation, cautery) are ineffective or impractical. For this study, SoC will be initiated with continuous firm manual compression with or without gauze or sponge and with or without a topical absorbable hemostat (example SURGICEL).	Other: Standard of Care (SoC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemostasis at the Target Bleeding Site (TBS) at 4-minutes Following Randomization	Proportion of subjects achieving hemostasis at the TBS at 4-minutes following randomization and with no re-bleeding requiring treatment at the TBS any time prior to initiation of wound closure. Hemostasis is defined as no detectable bleeding at the TBS.	Intraoperative, 4 minutes following randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemostasis at the Target Bleeding Site (TBS) at 10-minutes Following Randomization	Proportion of subjects achieving hemostatic success at 10 minutes following randomization and no further bleeding requiring treatment prior to initiation of wound closure.	Intraoperative, 10 minutes following randomization
Absolute Time to Hemostasis	The absolute time to achieve hemostasis at or after 4 minutes from randomization.	Intraoperative, an average of 4.2 minutes following randomization
Incidence of Re-bleeding Events From the TBS During the Study Follow-up		Up to 60-days following surgery
Incidence of Adverse Events (AEs)		Up to 60-days following surgery
Incidence of Adverse Events That Were Potentially Related to Thrombotic Events	Number of participants with adverse events that were potentially related to thrombic events	Up to 60-days following surgery

Collaborators and Investigators

• Sponsor: Ethicon, Inc.

Publications and helpful links

General Publications

• Corral M, Ferko N, Hollmann S, Hogan A, Jamous N, Batiller J, Shen J. Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials. Curr Med Res Opin. 2016;32(2):367-75. doi: 10.1185/03007995.2015.1128405. Epub 2015 Dec 21.
• Koea JB, Batiller J, Aguirre N, Shen J, Kocharian R, Bochicchio G, Garden OJ. A multicentre, prospective, randomized, controlled trial comparing EVARREST fibrin sealant patch to standard of care in controlling bleeding following elective hepatectomy: anatomic versus non-anatomic resection. HPB (Oxford). 2016 Mar;18(3):221-8. doi: 10.1016/j.hpb.2015.12.006. Epub 2016 Feb 1.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: November 19, 2013
• First Submitted That Met QC Criteria: November 22, 2013
• First Posted (ESTIMATE): November 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 11, 2016
• Last Update Submitted That Met QC Criteria: May 31, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Hepatobiliary Surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: BIOS-13-005; 2013-002535-24 (EUDRACT_NUMBER)