Safety and Efficacy Study of Fibrin Sealant Grifols Evaluated as an Adjunct to Hemostasis

A Prospective, Single-blind, Randomized, Phase II/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 evaluate the safety and hemostasis effectiveness of human plasma-derived fibrin sealant Grifols (FS Grifols) in peripheral vascular surgery.

Study Overview

• Status: Completed
• Conditions: Target Bleeding Site During Peripheral Vascular Surgery
• Intervention / Treatment: Biological: FS Grifols; Biological: FS Grifols; Procedure: Manual Compression

Detailed Description

The trial consisted of 2 parts: a Preliminary Part (I) and a Primary Part (II). All subjects enrolled in Preliminary Part (I) were treated with FS Grifols. Subjects in Primary Part (II) were randomly allocated in a 2:1 ratio to treatment with FS Grifols or manual compression. The objectives of the study were to evaluate the hemostasis effectiveness of FS Grifols in peripheral vascular surgery and to assess clinical safety, viral safety, and immunogenicity.

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Schulich School of Medicine, London Health Sciences Center
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Barcelona, Spain, 08208
    • Hospital de Sabadell
  • Palma de Mallorca, Spain, 07014
    • Hospital Son Espases
  • Pamplona, Spain, 31008
    • Clinica Universitaria de Navarra
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Hospital Universitario de Getafe
• United Kingdom
  • Doncaster, United Kingdom, DN2 5LT
    • Doncaster Royal Infirmary Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Tooting, United Kingdom, SW17 ORE
    • St. George's Hospital
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2WB
      • Queen Elizabeth Hospital Birmingham
  • Surrey
    • Frimley, Surrey, United Kingdom, GU16 7UJ
      • Frimley Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are male or female
• Must be at least 3 years of age with no upper age limit (must be at least 18 years of age in Spain and United Kingdom)
• Require an elective (non-emergency), open (non-laparoscopic; non-endovascular) peripheral vascular surgical procedure
• Have hemoglobin ≥ 9.0 g/dL
• Have platelet count > 70 x 10^3/mm^3

• Required one peripheral vascular procedure involving either an arterial patch angioplasty or an arterial anastomosis utilizing polytetrafluoroethylene or Dacron grafts, according to the Investigator's (the surgeon's) selection:

  1. Carotid endarterectomy requiring patch angioplasty
  2. Carotid-subclavian bypass grafting
  3. Axillo-femoral bypass grafting
  4. Abdominal aortic aneurysm resection and graft replacement
  5. Aorto-mesenteric bypass grafting
  6. Aorto-celiac bypass grafting
  7. Aorto-uni-iliac bypass grafting
  8. Aorto-bi-iliac bypass grafting
  9. Aorto-uni-femoral bypass grafting
  10. Aorto-bi-femoral bypass grafting
  11. Iliac aneurysm resection and graft replacement
  12. Femoral aneurysm resection and graft replacement
  13. Femoral-femoral bypass grafting
  14. Femoral-popliteal bypass grafting
  15. Renal arterial revascularization (bypass grafting)
  16. Renal arterial revascularization (endarterectomy with patch angioplasty)
  17. Popliteal artery revascularization (bypass grafting)
  18. Popliteal artery revascularization (endarterectomy with patch angioplasty)
  19. Femoral endarterectomy with patch angioplasty
  20. Ilio-femoral bypass grafting

• Intra-operative inclusion criterion:

  • A Target bleeding site (TBS)can be identified according to the Investigator's judgment, and the TBS has a mild or moderate arterial bleeding according to the Investigator's judgment

Exclusion Criteria:

• Weighed < 20 kg
• Have a pre-operative (at Baseline Assessments) international normalized ratio ≥ 2.0
• Have a pre-operative (at Baseline Assessments) activated partial thromboplastin time ratio ≥ 1.5
• Have a pre-operative (at Baseline Assessments) serum creatinine > 2 times the upper limit of the normal range
• Were undergoing a re-operative procedure on same arterial patch angioplasty or arterial anastomosis
• Have an infection in the anatomical surgical area
• Have a history of severe (e.g., anaphylactic) reactions to blood or any blood derived product
• Unwilling to receive blood products
• Have positive bleeding history
• Female who was pregnant or nursing
• Are known to abuse alcohol, opiates, psychotropic agents or other chemicals or drugs, or have done so within 12 months to the screening visit.
• Are currently participating in another investigational drug or device clinical study, or have participated within 3 months to the screening visit.
• Were previously included in this clinical trial (protocol number IG402)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FS Grifols Preliminary Part (I); Open label administration of FS Grifols to all subjects	Biological: FS Grifols; Fibrin Sealant Grifols (FS Grifols). Preliminary Part (I); Biological: FS Grifols; Fibrin Sealant Grifols (FS Grifols). Primary Part (II)
Experimental: FS Grifols Primary Part (II); Single-blind, randomized (2:1)	Biological: FS Grifols; Fibrin Sealant Grifols (FS Grifols). Preliminary Part (I); Biological: FS Grifols; Fibrin Sealant Grifols (FS Grifols). Primary Part (II)
Active Comparator: Manual Compression Primary Part (II); Single-blind, randomized (2:1)	Procedure: Manual Compression; Manual Compression. Primary Part (II)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Efficacy Endpoint is Time to Hemostasis.	The primary efficacy endpoint of the study is time to hemostasis (TTH), measured in minutes from the start of treatment application (TStart) at the TBS to the achievement of hemostasis at that site or to the end of the 10-minute observational period if hemostasis has not yet been achieved.	The start of treatment application at the target bleeding site (TBS) to the achievement of hemostasis at that site or to the end of the 10-minute observational period when the hemostasis has not yet been achieved.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions of Subjects Achieving Hemostasis	The cumulative proportions of subjects who achieved hemostasis during the 10- minute observation period in Primary Part (II)	10 minutes from the start of treatment application at the target bleeding site
Prevalence of Treatment Failures	The cumulative proportions of subjects who did not achieve hemostasis during the 10- minute observation period in Primary Part (II)	10 minutes from the start of treatment application at the target bleeding site

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.
• Investigators: Study Director: Louis Kozloff, MD, Independent

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: May 20, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (Estimate): May 26, 2008

Study Record Updates

• Last Update Posted (Estimate): January 25, 2016
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Hemostasis; Fibrin Sealant; Peripheral Vascular Surgery
• Other Study ID Numbers: IG402