Back to resultsThe EVARREST® Paediatric Mild/Moderate Liver and Soft Tissue Bleeding Study
Primary Purpose
Hemorrhage, Soft Tissue Bleeding, Hepatic Parenchyma Bleeding
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
EVARREST™ Sealant Matrix
SURGICEL®
Sponsored by
About this trial
This is an interventional treatment trial for Hemorrhage focused on measuring Fibrin Sealant, Hemostatics, Coagulants
Eligibility Criteria
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.
Sites / Locations
- Clinical Investigation Site #32
- Investigative Site #30
- Clinical Investigation Site #31
- Clinical Investigation Site #21
- Clinical Investigation Site #22
- Clinical Investigation Site #20
- Clinical Investigation Site #26
- Clinical Investigation Site #23
- Clinical Investigation Site #25
- Clinical Investigation Site #24
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
EVARREST™ Sealant Matrix
SURGICEL® Absorbable Hemostat
Arm Description
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).
SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Percentage of Participants With No Re-bleeding at the Target Bleeding Site
Percentage of participants with no re-bleeding at the TBS were reported.
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.
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.
Number of Participants Who Required Re-treatment At The Target Bleeding Site
Number of participants who required re-treatment at the TBS were reported.
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.
Change From Baseline to Post-surgery in Haemoglobin
Change from baseline to post-surgery in haemoglobin were reported.
Change From Baseline to Post-surgery in Haematocrit
Change from baseline to post-surgery in Haematocrit was reported.
Change From Baseline to Post-surgery in Platelet Count
Change from baseline to post-surgery in platelet count was reported.
Estimated Volume of Blood Loss
Estimated volume of intra-operative blood loss (including but not limited to the TBS) was reported.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02227992
Brief Title
The EVARREST® Paediatric Mild/Moderate Liver and Soft Tissue Bleeding Study
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
July 1, 2014 (Actual)
Primary Completion Date
October 27, 2021 (Actual)
Study Completion Date
November 12, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ethicon, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemorrhage, Soft Tissue Bleeding, Hepatic Parenchyma Bleeding
Keywords
Fibrin Sealant, Hemostatics, Coagulants
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EVARREST™ Sealant Matrix
Arm Type
Experimental
Arm Description
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).
Arm Title
SURGICEL® Absorbable Hemostat
Arm Type
Active Comparator
Arm Description
SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.
Intervention Type
Biological
Intervention Name(s)
EVARREST™ Sealant Matrix
Other Intervention Name(s)
EVARREST™ Fibrin Sealant Patch
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
SURGICEL®
Other Intervention Name(s)
oxidized regenerated cellulose
Intervention Description
SURGICEL® Absorbable Hemostat is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.
Primary Outcome Measure Information:
Title
Absolute Time to Haemostasis (TTH)
Description
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.
Time Frame
Up to 1 day (Intraoperative)
Title
Absolute Time to Haemostasis (TTH) by Age Group
Description
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.
Time Frame
Up to 1 day (Intraoperative)
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
4 minutes post randomization (up to 1 day; intraoperative)
Title
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
Description
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.
Time Frame
10 minutes post randomization (up to 1 day; intraoperative)
Title
Percentage of Participants With No Re-bleeding at the Target Bleeding Site
Description
Percentage of participants with no re-bleeding at the TBS were reported.
Time Frame
Up to 44 days post-surgery on Day 0
Title
Number of Participants With Adverse Events (AEs) That Were Potentially Related To Bleeding at the TBS
Description
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.
Time Frame
Up to 44 days post-surgery on Day 0
Title
Number of Participants With AEs That Were Potentially Related To Thrombotic Events
Description
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.
Time Frame
Up to 44 days post-surgery on Day 0
Title
Number of Participants Who Required Re-treatment At The Target Bleeding Site
Description
Number of participants who required re-treatment at the TBS were reported.
Time Frame
Up to 44 days post-surgery on Day 0
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
Up to 44 days post-surgery on Day 0
Title
Change From Baseline to Post-surgery in Haemoglobin
Description
Change from baseline to post-surgery in haemoglobin were reported.
Time Frame
From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0)
Title
Change From Baseline to Post-surgery in Haematocrit
Description
Change from baseline to post-surgery in Haematocrit was reported.
Time Frame
From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0)
Title
Change From Baseline to Post-surgery in Platelet Count
Description
Change from baseline to post-surgery in platelet count was reported.
Time Frame
From baseline up to hospital discharge (up to Day 44 post-surgery on Day 0)
Title
Estimated Volume of Blood Loss
Description
Estimated volume of intra-operative blood loss (including but not limited to the TBS) was reported.
Time Frame
Up to 1 day (intraoperative)
Title
Number of Participants Who Received Blood Transfusions
Description
Number of participants who received blood transfusions (red blood cells [RBCs], whole blood, fresh frozen plasma, platelets, and cryoprecipitates) were reported.
Time Frame
Up to 44 days post-surgery on Day 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
28 Days
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Kocharian, MD, PhD
Organizational Affiliation
Ethicon, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Investigation Site #32
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Investigative Site #30
City
Genk
Country
Belgium
Facility Name
Clinical Investigation Site #31
City
Gent
Country
Belgium
Facility Name
Clinical Investigation Site #21
City
Birmingham
Country
United Kingdom
Facility Name
Clinical Investigation Site #22
City
Leeds
Country
United Kingdom
Facility Name
Clinical Investigation Site #20
City
Liverpool
Country
United Kingdom
Facility Name
Clinical Investigation Site #26
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Clinical Investigation Site #23
City
London
Country
United Kingdom
Facility Name
Clinical Investigation Site #25
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Clinical Investigation Site #24
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
The EVARREST® Paediatric Mild/Moderate Liver and Soft Tissue Bleeding Study
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