Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) During Parenchymous Tissue Open Surgeries

A Prospective, Single-blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) as an Adjunct to Hemostasis During Parenchymous Tissue Open Surgeries

This study is designed to assess the safety and efficacy of Fibrin Sealant Grifols in patients undergoing open surgical procedures where bleeding may be present on parenchymous tissue (e.g., solid abdominal organs such as the liver). The purpose of this study is to demonstrate that Fibrin Sealant Grifols is not inferior to commercially-available oxidized cellulose pads (Surgicel®) in providing benefit in the time to hemostasis (i.e, the stoppage of bleeding). This study has a Preliminary Part (I) for study teams to become familiar with the application of Fibrin Sealant Grifols and to assess safety and a Primary Part (II) to assess the safety and efficacy of Fibrin Sealant Grifols. In both parts of the study, patients will be randomized in a 1:1 ratio to either Fibrin Sealant Grifols or Surgicel.

Study Overview

• Status: Completed
• Conditions: Parenchymous Tissue Surgical Bleeding
• Intervention / Treatment: Biological: Fibrin Sealant Grifols; Device: Surgicel®

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1082
    • 602
  • Pécs, Hungary, 7623
    • 600
• Russian Federation
  • Moscow, Russian Federation, 115478
    • 640
  • Saint-Petersburg, Russian Federation, 197758
    • 641
• Serbia
  • Belgrade, Serbia, 11000
    • 621, 622, 623
  • Niš, Serbia, 18000
    • 620, 625
  • Novi Sad, Serbia, 21000
    • 624
• United States
  • California
    • Loma Linda, California, United States, 92354
      • 224
    • Los Angeles, California, United States, 90033
      • 214
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • 213
  • Georgia
    • Augusta, Georgia, United States, 30912
      • 223
  • Illinois
    • Chicago, Illinois, United States, 60611
      • 228
  • Indiana
    • Goshen, Indiana, United States, 46526
      • 227
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • 207
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • 220
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • 229
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • 201
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • 231
  • New York
    • Albany, New York, United States, 12208
      • 200
    • New York, New York, United States, 10029
      • 211
    • New York, New York, United States, 10032
      • 212
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • 230
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • 233
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • 400
    • Philadelphia, Pennsylvania, United States, 19102
      • 218
    • Philadelphia, Pennsylvania, United States, 19107
      • 204
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • 205
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • 217
    • Nashville, Tennessee, United States, 37232-7610
      • 206
  • Texas
    • Houston, Texas, United States, 77030
      • 216, 219
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • 232
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • 226
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • 202

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline (within 24 hours prior to surgical procedure).
• Require elective (non-emergency), open (non-laparoscopic), hepatic resection (anatomic or non-anatomic resections of at least one anatomical hepatic segment, or equivalent tissue volume).
• A target bleeding site can be identified.
• Target bleeding site is identified on the cut raw liver surface (resection area).
• Target bleeding site has moderate bleeding according to the Investigator's judgment.

Exclusion Criteria:

• Require hepatic resection due to trauma.
• Infection in the anatomic surgical area.
• History of severe (e.g. anaphylactic) reactions to blood or to any blood-derived product.
• Previous known sensitivity to any Fibrin Sealant Grifols component or any Surgicel® component.
• Females who are pregnant or nursing a child at Baseline (within 24 hours prior to surgical procedure).
• Receiving an organ transplant during the same surgical procedure.
• Undergone a therapeutic surgical procedure within 30 days from the screening visit.
• A target bleeding site cannot be identified.
• The target bleeding site has a mild or severe bleeding.
• Occurrence of major intraoperative complications that require resuscitation or deviation from the planned surgical procedure.
• Application of any topical haemostatic material on the resection surface of the liver prior to application of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fibrin Sealant Grifols; Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).	Biological: Fibrin Sealant Grifols; Combination of 3 mL fibrinogen and 3 mL thrombin, in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to the target bleeding site.
Active Comparator: Surgicel®; Surgicel® is a sterile, absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.	Device: Surgicel®; Up to four Surgicel® sheets applied to the target bleeding site according to Package Insert instructions and the surgeon's usual clinical practice.; Other Names: Fibrillar absorbable hemostat; Oxidized regenerated cellulose hemostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start	Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.	From start of treatment until 4 minutes after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Achieving Hemostasis by Three Minutes After Treatment Start	Subjects achieving hemostasis at the target bleeding site by 3 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.	From start of treatment until 3 minutes after treatment start
Time to Hemostasis	Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start.	From start of treatment until 10 minutes after treatment start
Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points	Cumulative proportion of subjects having achieved hemostasis by each of the following time points: At 2 minutes following start of study treatment; At 5 minutes following start of study treatment; At 7 minutes following start of study treatment; At 10 minutes following start of study treatment	From start of treatment until 10 minutes after treatment start
Prevalence of Treatment Failures	Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.	From start of treatment until 10 minutes after treatment start

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 18, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimate): December 21, 2012

Study Record Updates

• Last Update Posted (Estimate): February 8, 2017
• Last Update Submitted That Met QC Criteria: December 16, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Fibrin Sealant; Parenchymous tissue open surgery; Hepatic Resection; Oxidized cellulose pads
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: IG1102