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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Vascular Surgical Bleeding

Intervention / Treatment
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* Biological: Fibrin Sealant Grifols
* Procedure: Manual Compression


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibrin Sealant Grifols<br>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<br>* Combination of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).<br>|
| Active Comparator: Manual Compression<br>Direct manual compression of target bleeding site with gauze/laparotomy pads. | Procedure: Manual Compression<br>* Direct manual compression of target bleeding site with gauze/laparotomy pads.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular Surgery, Fibrin Sealant, Polytetrafluoroethylene (PTFE) grafts