Fibrin Sealant VH S/D 500 S-apr in Hepatic Resection

Study Overview
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Brief Summary
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The purpose of the study is to compare safety and efficacy of Fibrin Sealant (FS) Vapor Heated (VH) S/D 500 s-apr with manual compression as a supportive treatment of local bleeding (i.e. oozing) in hepatic resection surgery when standard surgical techniques are insufficient.

Official Title
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A Randomized, Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Fibrin Sealant VH S/D 500 S-apr (Tisseel) for Hemostasis in Subjects Undergoing Hepatic Resection

Conditions
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Bleeding (Oozing) in Hepatic Resection

Intervention / Treatment
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* Drug: Fibrin Sealant (FS) VH S/D 500 s-apr
* Other: Manual compression


Participation Criteria
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Eligibility Criteria
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Pre-Operative Inclusion Criteria: Signed informed consent obtained from the subject before any study-related activities Subject's age is 18 years or above Subject will undergo planned, elective resection of at least 1 anatomical segment of the liver for any reason by laparotomy Subject is willing and able to comply with the requirements of the protocol Female subjects of childbearing potential must present with a negative serum or urine pregnancy test within 72 hours before the elective liver resection Female subjects of childbearing potential must agree to employ adequate birth control measures for the time of their participation in the study Intra-Operative Inclusion Criteria (before randomization): Resection of at least 1 anatomical segment of the liver has been performed Oozing from the cut surface of the liver persists after conventional resection procedure and primary control of arterial and venous bleeding by sutures, ligations, clips, vascular stapler, point electrocautery or focal radiofrequency ablation Need for additional supportive hemostatic treatment to stop bleeding (i.e. diffuse oozing) of the liver resection area Pre-Operative Exclusion Criteria: Subject needs emergency liver surgery Subject will undergo liver resection via laparoscopic procedure Subject has known congenital coagulation disorder (e.g. hemophilia) Subject has known hypersensitivity to any ingredient of the investigational medicinal product Suspected inability or unwillingness of the subject to comply with trial procedures If female, subject is pregnant or lactating at the time of study enrollment Subject has already participated in this study (each subject can only be enrolled once) Subject has participated in another clinical study involving an investigational product or investigational device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study Intra-operative Exclusion Criteria (before randomization): Occurrence of any severe surgical complication that require resuscitation or deviation from the planned surgical procedure Disseminated intravascular coagulopathy (DIC) Application of any topical hemostatic material on the resection surface of the liver prior to application of the study treatment Radiofrequency precoagulation of the liver resection surface, except focal use of radiofrequency as primary hemostatic treatment

Ages Eligible for Study
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Minimum Age: 18 Years

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FS VH S/D 500 s-apr<br>Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr), not to exceed 20mL per participant. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | Drug: Fibrin Sealant (FS) VH S/D 500 s-apr<br>* Dosage form: spray application; dosage frequency: single application<br>* Other names: Tisseel;|
| Active Comparator: Manual compression - Control<br>A dry surgical gauze swab will be used to apply by hand an even light pressure onto the oozing resection surface of the liver. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | Other: Manual compression<br>* Dosage form: surgical gauze swab; dosage frequency: single application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Intraoperative Hemostasis at 4 Minutes After Treatment Application | Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression. The following were regarded as treatment failures: No hemostasis achieved at 4 minutes post treatment application (for the FS VH S/D 500 s-apr arm, the time to hemostasis was used; a time window of +5 seconds was acceptable for showing a success) Additional hemostatic treatment (ie, hemostatics in addition to the randomized treatment) was required Reapplication of FS VH S/D 500 s-apr after 4 minutes Intraoperative rebleeding after the first 4 minutes of the observation period | 4 minutes post start of treatment application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Intraoperative Hemostasis at 6 Minutes After Application of the Randomized Treatment | Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression. | 6 minutes after start of treatment application | 
| Percentage of Participants With Intraoperative Hemostasis at 8 Minutes After Application of the Randomized Treatment | Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression. | 8 minutes after start of treatment application | 
| Percentage of Participants With Intraoperative Hemostasis at 10 Minutes After Application of the Randomized Treatment | Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression. | 10 minutes after start of treatment application | 
| Percentage of Participants With Intraoperative Rebleeding After Occurrence of Hemostasis | Intraoperative rebleeding from the treated liver resection surface after occurrence of hemostasis. | Intraoperative day 0 | 
| Percentage of Participants With Postoperative Rebleeding | Rebleeding until discharged from the surgical ward, defined as any rebleeding from the treated liver resection surface requiring surgical reexploration | Postoperative until discharged from surgical ward | 
| Percentage of Participants With Transfusion Requirements Until Discharged From Surgical Ward | Transfusions administered included whole blood, packed red blood cells, fresh frozen plasma, and thrombocyte concentrate. | Intra- and postoperative until discharged from surgical ward | 
| Median Total Volume of Postoperative Drainage Fluid Within 48 Hours After Surgery |  | Within 48 hours after surgery |