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

Hemorrhage Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02227992
• Other study ID #: 400-12-004
• Secondary ID: 2013-003557-24
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2014
• Est. completion date: November 12, 2021

Study information

• Verified date: October 2022
• Source: Ethicon, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 12, 2021
• Est. primary completion date: October 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Days to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Hepatic Parenchyma Bleeding
• Soft Tissue Bleeding

Intervention

Biological:
• EVARREST™ Sealant Matrix
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.

Device:
• SURGICEL®
SURGICEL® Absorbable Hemostat is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.

Locations

Country	Name	City	State
Belgium	Clinical Investigation Site #32	Brussels
Belgium	Investigative Site #30	Genk
Belgium	Clinical Investigation Site #31	Gent
United Kingdom	Clinical Investigation Site #21	Birmingham
United Kingdom	Clinical Investigation Site #22	Leeds
United Kingdom	Clinical Investigation Site #20	Liverpool
United Kingdom	Clinical Investigation Site #23	London
United Kingdom	Clinical Investigation Site #26	London
United Kingdom	Clinical Investigation Site #25	Nottingham
United Kingdom	Clinical Investigation Site #24	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Ethicon, Inc.

Countries where clinical trial is conducted

Belgium,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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