A Study of Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Haemostasis During Surgery in Paediatric Participants

Study Overview
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Brief Summary
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The objective of the study is to evaluate if FS Grifols is non-inferior to EVICEL® in terms of the percentage of participants achieving hemostasis at the target bleeding site (TBS) by 4 minutes (T4) from the start of treatment application (TStart) with no occurrence of rebleeding until the completion of the surgical closure by layers of the exposed surgical field containing the TBS (TClosure).

Detailed Description
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This is a prospective, randomized, active-controlled, single-blind, parallel group clinical trial to evaluate the safety and efficacy of FS Grifols as an adjunct to hemostasis during surgery. Approximately 172 pediatric participants will be enrolled and will be randomly allocated in a 1:1 ratio into 1 of 2 treatment groups: FS Grifols or EVICEL. Enrollment will be monitored by surgery type to ensure at least 50% of the surgical procedures are hepatic. A specific bleeding site will be defined as the TBS when it is determined by the investigator (the surgeon) that control of bleeding by conventional surgical techniques (including suture, ligature, and cautery) is ineffective or impractical and requires an adjunct treatment to achieve hemostasis. When the TBS is identified, the investigator will record the precise anatomical location of the TBS, rate the intensity of the bleeding at the TBS (Grade 1-4 according to a 5-point validated bleeding severity scale), and record the size of the approximate bleeding surface, (small, medium, and large). For soft tissue surgery only, the investigator will also record the type of soft tissue (ie, fat, muscle, or connective tissue). In this clinical trial, only participants with a TBS with bleeding of Grade 1 (mild) or Grade 2 (moderate) intensity will be enrolled. This study includes a Screening Visit to determine participant eligibility, a Baseline Visit, the Surgical Procedure (Day 1), and Post-operative assessments at Days 1, 4, and 30. The total duration of a participant's participation in this study is expected to be no longer than 2 months from the Screening Visit to the Post-operative Day 30 Visit.

Official Title
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A Prospective, Randomized, Active-Controlled, Single-blind, Parallel Group Clinical Trial to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) as an Adjunct to Haemostasis During Surgery in Paediatric Subjects

Conditions
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Excessive Bleeding During Surgery

Intervention / Treatment
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* Biological: Fibrin Sealant Grifols
* Biological: EVICEL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-operative: Less than 18 years of age. Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure. Participant and/or participant's legal guardian is willing to give permission for the participant to participate in the clinical trial and provide written informed consent for the participant. In addition, assent must be obtained from pediatric participants who possess the intellectual and emotional ability to comprehend the concepts involved in the clinical trial. Intra-operative: Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft tissue TBS identified intra-operatively by the investigator (the surgeon). TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the investigator's (the surgeon's) judgment. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale. Exclusion Criteria: Pre-operative: Admitted for trauma surgery. Unwilling to receive blood products. Known history of severe (eg, anaphylactic) reaction to blood products. Known history of intolerance to any of the components of the investigational product (IP). Female participants who are pregnant, breastfeeding or, if of child-bearing potential (ie, adolescent), unwilling to practice a highly effective method of contraception. Previously enrolled in a clinical trial with FS Grifols. Currently participating, or during the study is planned to participate, in any other investigational device or medicinal product study without prior and explicit approval from the sponsor. Intra-operative: An appropriate parenchymous or soft tissue TBS (as defined in exclusion criteria 9 and 10) cannot be identified intra-operatively by the investigator (the surgeon). TBS has Grade 3 (severe) bleeding according to the investigator's (the surgeon's) judgment that cannot be controlled with conventional surgical techniques to Grade 1 or Grade 2 bleeding. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale. TBS is in an actively infected surgical field. Occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure. Application of any topical hemostatic agent on the resection surface of parenchyma or soft tissue prior to application of the IP.

Ages Eligible for Study
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Maximum Age: 17 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: Fibrin Sealant Grifols<br>Participants topically applied FS Grifols, which consisted of component 1: human fibrinogen (80 mg/mL) and component 2: human thrombin with calcium chloride (500 IU/mL) solutions filled in syringes and assembled on a syringe holder. | Biological: Fibrin Sealant Grifols<br>* The FE Grifols solution was applied topically via drip or spray application.<br>* Other names: FS Grifols;|
| Active Comparator: EVICEL<br>Participants topically applied EVICEL, which consisted of component 1: Concentrate of human fibrinogen (BAC 2) (55-85 mg/mL) and component 2: human thrombin (800-1200 IU/mL) solutions. The 2 components (BAC2 and thrombin) were mixed and applied topically. | Biological: EVICEL<br>* The EVICEL solution was applied topically via drip or spray application.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hemostasis Within 4 Minutes After Treatment Start (T4) | Hemostasis is defined as Grade 0 bleeding per 5-point validated bleeding severity scale (0=no bleeding and 4=Unidentified or inaccessible spurting or gush) at the target bleeding site (TBS) according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin. | From start of treatment until 4 minutes after treatment start (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Percentage of Participants Achieving Hemostasis at the TBS by the 7 Minutes After Treatment Start (T7) | Hemostasis is defined as Grade 0 bleeding at the TBS according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin. The cumulative percentage of participants achieving hemostasis at the TBS by the time points of T7 defined as an absence/cessation of bleeding (Grade 0) at the TBS by that time point without occurrence of rebleeding, Grade 3 or Grade 4 bleeding, use of alternative hemostatic treatment, and reapplication of study treatment after T4 and until TClosure. | From start of treatment to 7 minutes after start of treatment (Day 1) | 
| Cumulative Percentage of Participants Achieving Hemostasis at the Target Bleeding Site by 10 Minutes After Treatment Start (T10) | Hemostasis is defined as Grade 0 bleeding at the TBS according to the investigator's (surgeon's) judgment, so that the surgical closure of the exposed field could begin. The cumulative percentage of participants achieving hemostasis at the TBS by the time points of T10 defined as an absence/cessation of bleeding (Grade 0) at the TBS by that time point without occurrence of rebleeding, Grade 3 or Grade 4 bleeding, use of alternative hemostatic treatment, and reapplication of study treatment after T4 and until TClosure. | From start of treatment to 10 minutes after start of treatment (Day 1) | 
| Percentage of Participants With Treatment Failures | Participants were considered treatment failures if there is a. persistent bleeding at the TBS beyond T4 b. Grade 3 or Grade 4 breakthrough bleeding from the TBS that jeopardizes participant safety according to the investigator's judgment at any moment during the 10-minute observational period and until TClosure c. Use of alternative hemostatic treatments or maneuvers (other than the study treatment) at the TBS during the 10-minute observational period and until TClosure, or use of study treatment at the TBS beyond T4 and until TClosure d. Rebleeding (Grade ≥1) at the TBS after the assessment of the primary efficacy endpoint at T4 and until TClosure. | From start of treatment to 10 minutes after start of treatment and until the time of completion of surgical closure (Day 1) |