The Paediatric EVICEL® Soft Tissue and Parenchymal Organ Bleeding Study

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

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

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Soft Tissue Bleeding
• Intervention / Treatment: Biological: EVICEL® Fibrin Sealant; Device: SURGICEL® Absorbable Hemostat

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Clinical Investigation Site #31
• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Clinical Investigation Site #42
    • Toronto, Ontario, Canada
      • Clinical Investigation Site #40
  • Quebec
    • Montreal, Quebec, Canada
      • Clinical Investigation Site #41
• United Kingdom
  • Birmingham, United Kingdom
    • Clinical Investigation Site #21
  • Leeds, United Kingdom
    • Clinical Investigation Site #22
  • Liverpool, United Kingdom
    • Clinical Investigation Site #20
  • London, United Kingdom, SE1 7EH
    • Clinical Investigation Site #27
  • London, United Kingdom
    • Clinical Investigation Site #23
  • London, United Kingdom
    • Clinical Investigation Site #26
  • Newcastle, United Kingdom
    • Clinical Investigation Site #30
  • Nottingham, United Kingdom, NG7 2UH
    • Clinical Investigation Site #25
  • Southampton, United Kingdom
    • Clinical Investigation Site #24

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVICEL® Fibrin Sealant; 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; 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; Other Names: EVICEL, fibrin sealant
Active Comparator: SURGICEL® Absorbable Hemostat; SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.	Device: SURGICEL® Absorbable Hemostat; SURGICEL® Absorbable Hemostat (oxidized regenerated cellulose) is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.; Other Names: oxidized regenerated cellulose

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Thrombotic Event	Number of Participants with a Thrombotic Event.	From randomisation up to 30 days (+/- 14 days) following surgery
Number of Participants With an Adverse Event Related to Re-bleeding at Target Bleeding Site	Number of Participants with an Adverse Event Related to Re-bleeding at Target Bleeding Site.	From randomisation to 30 days (+/- 14 days) following surgery

Collaborators and Investigators

• Sponsor: Ethicon, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): April 17, 2019
• Study Completion (Actual): May 17, 2019

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimate): August 28, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Fibrin Sealant; Hemostatics; Coagulants
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: 400-12-006; 2013-003401-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes