Safety and Efficacy Study of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Peripheral Vascular Surgery

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 Peripheral Vascular Surgery

The purpose of this study is to demonstrate that the application of Fibrin Sealant Grifols provides a measurable benefit when compared to hemostasis achieved through conventional surgical technique (suture) and by standard hemostatic action, such as mechanical pressure through manual compression. This study has a Preliminary Part (I) in which all subjects are treated with Fibrin Sealant Grifols and a Primary Part (II) in which subjects are randomized in a 2:1 ratio to either Fibrin Sealant Grifols or manual compression.

Study Overview

• Status: Completed
• Conditions: Vascular Surgical Bleeding
• Intervention / Treatment: Biological: Fibrin Sealant Grifols; Procedure: Manual Compression

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Miskolc, Hungary, 03526
    • 501
  • Pecs, Hungary, 07623
    • 500
  • Veszprém, Hungary, 8200
    • 502
• Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • 540
  • Rostov-on-Don, Russian Federation, 344022
    • 542
  • Saint-Petersburg, Russian Federation, 194354
    • 541
  • Saint-Petersburg, Russian Federation, 195271
    • 543
  • Saint-Petersburg, Russian Federation, 197374
    • 544
• Serbia
  • Belgrade, Serbia, 11000
    • 523
  • Belgrade, Serbia, 11040
    • 521
  • Novi Sad, Serbia, 21000
    • 522,524
• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • 407
  • California
    • Palo Alto, California, United States, 94304
      • 125
    • San Diego, California, United States, 92120
      • 119
  • Florida
    • Jacksonville, Florida, United States, 32207
      • 149
    • Jacksonville, Florida, United States, 32216
      • 148
    • Tampa, Florida, United States, 33606
      • 137
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • 140
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • 114
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • 110
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • 146
    • New Orleans, Louisiana, United States, 70112
      • 132
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • 129
    • Bethesda, Maryland, United States, 20889
      • 135
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • 102
  • New York
    • Bronx, New York, United States, 10467-2401
      • 142
    • Manhasset, New York, United States, 11030
      • 406
    • Stony Brook, New York, United States, 11794
      • 113
  • Ohio
    • Dayton, Ohio, United States, 45409
      • 409
    • Toledo, Ohio, United States, 43606
      • 104
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • 100, 128
    • West Reading, Pennsylvania, United States, 19611
      • 115
  • Texas
    • Fort Worth, Texas, United States, 76107
      • 147
    • Houston, Texas, United States, 77024
      • 402
  • Utah
    • Salt Lake City, Utah, United States, 84132-3201
      • 139
  • Washington
    • Seattle, Washington, United States, 98104
      • 103
    • Tacoma, Washington, United States, 98431
      • 138
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • 111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• 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), primary, open (non-laparoscopic; non-endovascular) peripheral vascular surgery.
• Require one of the following peripheral vascular procedures involving proximal end-to-side arterial anastomosis utilizing coated or uncoated Polytetrafluoroethylene grafts: a) Femoral-femoral bypass grafting, b) Femoral-popliteal bypass grafting, c) Femoral-distal bypass grafting, d) Ilio-iliac bypass grafting, e) Ilio-femoral bypass grafting, f) Ilio-popliteal bypass grafting, g) Aorto-iliac bypass grafting, h) Aorto-femoral bypass grafting, i)Axillo-femoral bypass grafting, and j) Upper extremity vascular access for hemodialysis.
• A target bleeding site can be identified.
• Target bleeding site has moderate arterial bleeding.

Exclusion Criteria:

• Undergoing a re-operative procedure.
• Undergoing other vascular procedures during the same surgical session (stenting and/or endarterectomy of the same artery are allowed).
• Have an infection in the anatomic surgical area.
• Have a history of severe (e.g. anaphylactic) reactions to blood or to any blood-derived product.
• Have previous known sensitivity to any Fibrin Sealant Grifols, heparin, or protamine component.
• Females who are pregnant or nursing a child at Baseline (within 24 hours prior to surgical procedure).
• Have undergone a therapeutic surgical procedure within 30 days from the screening visit.
• Target bleeding site cannot be identified.
• Target bleeding site has mild or severe arterial bleeding.
• Occurrence of 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL

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).
ACTIVE_COMPARATOR: Manual Compression; Direct manual compression of target bleeding site with gauze/laparotomy pads.	Procedure: Manual Compression; Direct manual compression of target bleeding site with gauze/laparotomy pads.

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
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
Time to Hemostasis (TTH)	Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start. In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated. All calculations were performed using SAS PROC LIFETEST	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 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

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: August 7, 2012
• First Submitted That Met QC Criteria: August 8, 2012
• First Posted (ESTIMATE): August 10, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2017
• Last Update Submitted That Met QC Criteria: February 21, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Vascular Surgery; Fibrin Sealant; Polytetrafluoroethylene (PTFE) grafts
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: IG1101