The EVARREST® Paediatric Mild/Moderate Liver and Soft Tissue Bleeding Study

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and effectiveness of EVARREST™ Sealant Matrix (EVARREST™ Fibrin Sealant Patch) (EVARREST™) in controlling mild or moderate soft tissue & parenchymal bleeding during open hepatic, abdominal, pelvic, retroperitoneal, and thoracic (non-cardiac) surgery in paediatric patients.

Detailed Description
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This is an open label, prospective, randomised, multicentre, controlled, clinical study comparing EVARREST to SURGICEL (oxidized regenerated cellulose (ORC)) (Control) as an adjunct to haemostasis when conventional methods of controlling mild or moderate bleeding are ineffective or impractical during surgery in paediatric patients. At least 40 qualified paediatric subjects with an appropriate mild or moderate bleeding Target Bleeding Site (TBS) will be randomised in a 1:1 allocation ratio to either EVARREST or SURGICEL (control). Absolute time to haemostasis will be assessed as well as haemostasis at 4 and 10 minutes from randomisation. Enrolment will be staggered by age (as required by the European Medicines Agency (EMA) Paediatric Committee). The first 36 subjects enrolled will be aged ≥1 years to <18 years of age. Enrolment of a subsequent group will include 4 subjects from 1 month (≥ 28 days from birth) to <1 year of age will follow. Ongoing safety assessment will ensure adequate safety monitoring occur during the staged enrolment. 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 the Safety and Effectiveness of EVARREST® Sealant Matrix in Controlling Mild or Moderate Hepatic Parenchyma or Soft Tissue Bleeding During Open Abdominal, Retroperitoneal, Pelvic and Thoracic (Non-cardiac) Surgery in Paediatric Patients

Conditions
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Hemorrhage, Soft Tissue Bleeding, Hepatic Parenchyma Bleeding

Intervention / Treatment
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* Biological: EVARREST™ Sealant Matrix
* Device: SURGICEL®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paediatric subjects aged ≥28 days (≥ 1 month) to <18 years, requiring non-emergent open hepatic, abdominal, retroperitoneal, pelvic or thoracic (non-cardiac) surgical procedures. i) The first 36 subjects to be enrolled will be subjects aged ≥1 years to <18 years. ii) The next 4 subjects to be enrolled will be subjects aged ≥28 days to <1 year. The subject's parent/legal guardian must be willing to give permission for the subject to participate in the trial, and provide written informed consent for the subject. In addition, 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. Presence of an appropriate mild or moderate bleeding soft tissue or hepatic parenchyma Target Bleeding Site (TBS) identified intra-operatively by the surgeon; Ability to firmly press trial treatment at TBS until 4 minutes after randomisation 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 plans to participate in any other investigational device or drug 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. Subject with TBS in an actively infected field (Class III Contaminated or Class IV Dirty or Infected) TBS is from large defects in arteries or veins where the injured vascular wall requires repair with maintenance of vessel patency and which would result in persistent exposure of the EVARREST™ or SURGICEL® to blood flow and pressure during healing and absorption of the product; TBS with major arterial bleeding requiring suture or mechanical ligation; Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony confine.

Ages Eligible for Study
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Minimum Age: 28 Days
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: EVARREST™ Sealant Matrix<br>EVARREST™ Sealant Matrix/Fibrin Sealant Patch is a sterile bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of two biological components (Human Fibrinogen and Human Thrombin). | Biological: EVARREST™ Sealant Matrix<br>* EVARREST® Fibrin Sealant Patch is a sterile, bio-absorbable combination product, comprised of two biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.<br>* Other names: EVARREST™ Fibrin Sealant Patch;|
| 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®<br>* SURGICEL® Absorbable Hemostat 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 (TTH) | Absolute TTH, defined as the absolute time elapsed from randomization to the last moment in time at which detectable bleeding at the target bleeding site (TBS) was observed. | Up to 1 day (Intraoperative) | 
| Absolute Time to Haemostasis (TTH) by Age Group | Absolute TTH, defined as the absolute time elapsed from randomization to the last moment in time at which detectable bleeding at the TBS was observed. | Up to 1 day (Intraoperative) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Haemostatic Success at 4 Minutes Following Randomization With No Bleeding Requiring Treatment at the Target Bleeding Site Occurring Any Time Prior to Final Fascial Closure | Percentage of participants achieving haemostatic success at 4 minutes following randomization with no bleeding requiring treatment at the TBS occurring any time prior to final fascial closure were reported. | 4 minutes post randomization (up to 1 day; intraoperative) | 
| Percentage of Participants Achieving Haemostatic Success at 10 Minutes Following Randomization With No Bleeding Requiring Treatment at the Target Bleeding Site Occurring Any Time Prior to Final Fascial Closure | Percentage of participants achieving haemostatic success at 10 minutes following randomization with no bleeding requiring treatment at the TBS occurring any time prior to final fascial closure were reported. | 10 minutes post randomization (up to 1 day; intraoperative) | 
| Percentage of Participants With No Re-bleeding at the Target Bleeding Site | Percentage of participants with no re-bleeding at the TBS were reported. | Up to 44 days post-surgery on Day 0 | 
| Number of Participants With Adverse Events (AEs) That Were Potentially Related To Bleeding at the TBS | Number of participants With AEs that were potentially related to bleeding at the TBS were reported. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 44 days post-surgery on Day 0 | 
| Number of Participants With AEs That Were Potentially Related To Thrombotic Events | Number of participants with AEs that were potentially related to thrombotic events (sponsor assessment) were reported. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 44 days post-surgery on Day 0 | 
| Number of Participants Who Required Re-treatment At The Target Bleeding Site | Number of participants who required re-treatment at the TBS were reported. | Up to 44 days post-surgery on Day 0 | 
| Number of Participants With Adverse Events | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 44 days post-surgery on Day 0 | 
| Change From Baseline to Post-surgery in Haemoglobin | Change from baseline to post-surgery in haemoglobin were reported. | From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0) | 
| Change From Baseline to Post-surgery in Haematocrit | Change from baseline to post-surgery in Haematocrit was reported. | From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0) | 
| Change From Baseline to Post-surgery in Platelet Count | Change from baseline to post-surgery in platelet count was reported. | From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0) | 
| Estimated Volume of Blood Loss | Estimated volume of intra-operative blood loss (including but not limited to the TBS) was reported. | Up to 1 day (intraoperative) | 
| Number of Participants Who Received Blood Transfusions | Number of participants who received blood transfusions (red blood cells [RBCs], whole blood, fresh frozen plasma, platelets, and cryoprecipitates) were reported. | Up to 44 days post-surgery on Day 0 | 

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