The Paediatric EVICEL® Soft Tissue and Parenchymal Organ Bleeding Study

Study Overview
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Brief Summary
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To evaluate the safety and effectiveness of EVICEL® Fibrin Sealant (Human) as an adjunct to achieve haemostasis during surgery in paediatric patients.

Detailed Description
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This is a prospective, randomized, controlled, clinical study comparing EVICEL® to SURGICEL®, as an adjunct to haemostasis when conventional methods of controlling bleeding are ineffective or impractical during surgery in paediatric patients. At least 40 qualified paediatric subjects with an appropriate mild or moderate Target Bleeding Site (TBS) will be randomized in a 1:1 allocation ratio to either EVICEL® or SURGICEL®. Haemostasis will be assessed at 4, 7 and 10 minutes from randomization. Enrolment will be staggered by age (as required by the European Medicines Agency (EMA) Paediatric Committee). The first group enrolled will include at least 36 subjects aged ≥1 years to <18 years of age. When enrolment of the first group is complete; enrolment of a subsequent group will commence and include at least 4 subjects from birth (including neonates ≤37 weeks gestation) to <1 years of age. Subjects will be followed post-operatively through hospital discharge and at 30 days (±14 days) post-surgery.

Official Title
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A Prospective, Randomized, Controlled Study Evaluating EVICEL® Fibrin Sealant as an Adjunct to Haemostasis During Abdominal, Retroperitoneal, Pelvic or Thoracic (Non-Cardiac) Surgery in Paediatric Patients

Conditions
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Hemorrhage, Soft Tissue Bleeding

Intervention / Treatment
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* Biological: EVICEL® Fibrin Sealant
* Device: SURGICEL® Absorbable Hemostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paediatric subjects birth to <18 years of age, requiring non-emergent laparoscopic or open (through peritoneum or pleura) abdominal, retroperitoneal, pelvic or thoracic (non-cardiac) surgical procedures. i) The first 36 subjects to be enrolled will be subjects ≥1 years to <18 years of age. ii) The next 4 subjects to be enrolled will be subjects birth to <1years of age. The subject and/or subject's parent or legal guardian must be willing to give permission for the subject to participate in the trial, and provide written informed consent for the subject. If possible, assent must be obtained from paediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the trial. If the paediatric subject is not able to provide assent (due to age, maturity and/or inability to intellectually and/or emotionally comprehend the trial), the parent/legal guardian's written informed consent for the subject will be acceptable for the subject to be included in the study; and Presence of an appropriate mild or moderate bleeding soft tissue or parenchymal organ Target Bleeding Site identified intra-operatively by the surgeon; Exclusion Criteria: Subjects with known intolerance to blood products or to one of the components of the study product or is unwilling to receive blood products; Female subjects, who are of childbearing age (i.e. adolescent), who are pregnant or nursing; Subject is currently participating or, during the study is planned to participate in any other investigational device or drug trial without prior approval from the Sponsor; Subjects who are known, current alcohol and/or drug abusers; Subjects admitted for trauma surgery; Subjects with any pre or intra-operative findings identified by the surgeon that may preclude conduct of the study procedure; Subjects with Target Bleeding Site in an actively infected field (Class III Contaminated or Class IV Dirty or Infected) Anastomotic bleeding sites will not be considered for randomization.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EVICEL® Fibrin Sealant<br>EVICEL® is a human plasma-derived fibrin sealant. EVICEL® consists of two components: a concentrate of Human Clottable Protein (referred to as Biological Component 2; BAC2) and a solution of Human Thrombin. No material of animal origin is present in the product | Biological: EVICEL® Fibrin Sealant<br>* EVICEL® is a human plasma-derived fibrin sealant. EVICEL® consists of two components: a concentrate of Human Clottable Protein (referred to as Biological Component 2; BAC2) and a solution of Human Thrombin. No material of animal origin is present in the product<br>* Other names: EVICEL, fibrin sealant;|
| Active Comparator: SURGICEL® Absorbable Hemostat<br>SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose. | Device: SURGICEL® Absorbable Hemostat<br>* SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.<br>* Other names: oxidized regenerated cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Time to Haemostasis | Absolute time to haemostasis, defined as absolute time when there was no detectable bleeding at the Target Bleeding Site (TBS). | From randomisation (identification of appropriate target bleeding site) to final fascial closure (median study procedure time 164.0 minutes [range 47.0 - 506.0 minutes]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Haemostasis at 4 Minutes | Number of participants achieving haemostasis at target bleeding site at 4 minutes. This endpoint is assessing haemostasis at 4 minutes only and not maintenance of haemostasis following this timepoint. As rebleeding may occur between timepoints, subsequent rebleeding (if any) is detailed in treatment failure analysis. | Intra-operatively from randomisation to 4 minutes after randomisation | 
| Number of Participants Achieving Haemostasis at 7 Minutes | Number of Participants Achieving Haemostasis at Target Bleeding Site at 7 Minutes. This endpoint is assessing haemostasis at 7 minutes only and is not affected by haemostasis assessment prior to 7 minutes or maintenance of haemostasis following this 7 minute assessment. As rebleeding may occur between timepoints, subsequent rebleeding (if any) is detailed in treatment failure analysis. | Intra-operatively from randomisation to 7 minutes after randomisation | 
| Number of Participants Achieving Haemostasis at 10 Minutes | Number of Participants Achieving Haemostasis at Target Bleeding Site at 10 Minutes. This endpoint is assessing haemostasis at 10 minutes only and is not affected by haemostasis assessments prior to 10 minutes or maintenance of haemostasis following this 10 minute assessment. As rebleeding may occur between timepoints, subsequent rebleeding (if any) is detailed in treatment failure analysis). | Intra-operatively from randomisation to 10 minutes after randomisation | 
| Incidence of Treatment Failures (Number of Participants) | Defined as haemostasis not achieved within 10 minutes or bleeding requiring treatment other than re-application of the assigned haemostatic adjunct within 10 minutes. | 10 minutes | 
| Estimated Blood Loss | Blood loss during surgical procedure (includes but not limited to the target bleeding site) | During surgical procedure (first incision to final fascial closure (median study procedure time 164.0 minutes [range 47.0 - 506.0 minutes]) | 
| Blood Transfusion | Participants requiring a blood transfusion | From surgical procedure to 30 day (+/-14 day) follow-up visit | 
| Participants Receiving a Blood Transfusion | Details of blood products received (if any) | From surgery to 30 day (+/-14 day) follow-up visit | 
| Changes in Laboratory Parameters Haemoglobin and Mean Corpuscular Haemoglobin Concentration | Laboratory parameter changes from baseline to post operative hospital discharge (Haemoglobin and Mean Corpuscular Haemoglobin Concentration) | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Haematocrit | Change in red blood cell proportion in volume in the blood from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Platelet Count and White Cell Count | Laboratory parameter changes from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours) | 
| Changes in Laboratory Parameters Red Blood Cell Count | Laboratory parameter changes from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Mean Corpuscular Haemoglobin | Laboratory parameter changes from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Mean Corpuscular Volume | Laboratory parameter changes from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils | Laboratory parameter changes in volume from baseline to post operative hospital discharge (Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils) | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters Activated Partial Thromboplastin Time and Prothrombin Time | Laboratory parameter changes from baseline to post operative hospital discharge (Activated Partial Thromboplastin Time and Prothrombin Time) | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 
| Changes in Laboratory Parameters International Normalised Ratio | Standardized measurement of the change in blood clotting time from baseline to post operative hospital discharge | Baseline (within 21 days prior to surgery) to Hospital Discharge (within 72 hours of discharge) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibrin Sealant, Hemostatics, Coagulants