The EVARREST® Pediatric Mild or Moderate Liver and Soft Tissue Bleeding Study

This is an open-label, multicenter, single-arm study evaluating the safety and effectiveness of EVARREST in controlling mild or moderate bleeding in hepatic parenchyma or soft tissue for which standard methods of achieving hemostasis are ineffective or impractical.

Eligible subjects will be treated with EVARREST. Subjects will be followed post-operatively through discharge and at 30 days (+/-14 days) post-surgery.

At least thirty-five pediatric subjects with an appropriate mild or moderate bleeding target bleeding site (TBS) will be enrolled in this study. The age of the subjects enrolled in the study will be from 1 month to less than (<) 18 years. This will include a minimum of 4 subjects aged 1 month (greater than or equal to \[>=\] 28 days from birth) to <1 year.

• EVARREST® Fibrin Sealant Patch (Biological), also known as EVARREST: EVARREST Fibrin Sealant Patch is a sterile, bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.

Primary outcomes

• Absolute Time to Hemostasis [During surgical procedure on Day 0 (from TBS identification to the last moment in time at which detectable bleeding at TBS observed)]: Hemostasis was defined as no detectable bleeding at the TBS. Absolute time to hemostasis was defined as the absolute time elapsed from TBS identification to the last moment in time at which detectable bleeding at the TBS was observed. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression.

Secondary outcomes

• Percentage of Participants Who Achieved Hemostatic Success at 4 Minutes [4 minutes after TBS identification (during surgical procedure on Day 0)]: Percentage of participants who achieved hemostatic success at 4 minutes was reported. A participant was considered hemostatic success at 4 minutes if the TBS was hemostatic at 4 minutes, and there was no re-bleeding that required treatment (other than observation only) at the TBS from 4 minutes following the first TBS identification through final fascial closure. Hemostasis was assessed at 4 minutes from TBS identification by carefully releasing manual compression and removing the surgical sponge (if used). TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression.
• Percentage of Participants Who Achieved Hemostatic Success at 10 Minutes [10 minutes after TBS identification (during surgical procedure on Day 0)]: Percentage of participants who achieved hemostatic success at 10 minutes was reported. A participant was considered hemostatic success at 10 minutes if the TBS was hemostatic at 10 minutes, and there was no re-bleeding that required treatment (other than observation only) at the TBS from 10 minutes following the first TBS identification through final fascial closure. Hemostasis was assessed at 10 minutes from TBS identification and at initiation of final fascial closure. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression.
• Percentage of Participants With No Re-bleeding at the TBS [During surgical procedure on Day 0 (from TBS identification to final fascial closure)]: Percentage of participants with no re-bleeding at the TBS was reported. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression.
• Percentage of Participants With Adverse Events That Were Potentially Related to Bleeding at the TBS [From the day of surgical procedure (Day 0) up to 44-days post-surgery]: Percentage of participants with adverse events that were potentially related to bleeding at the TBS was reported. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression. An adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, without judgment about causality.
• Percentage of Participants With Adverse Events That Were Potentially Related to Thrombotic Events [From the day of surgical procedure (Day 0) up to 44-days post-surgery]: Percentage of participants with adverse events that were potentially related to thrombotic events at the TBS was reported. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression. An adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, without judgment about causality.
• Percentage of Participants With Re-treatment at the TBS [From the day of surgical procedure (Day 0) up to 44-days post-surgery]: Percentage of participants with re-treatment at the TBS was reported. TBS was defined as the first accessible mild or moderate bleeding site identified in the hepatic parenchyma or soft tissue, where conventional methods of controlling bleeding were ineffective or impractical and was amenable to manual compression.
• Percentage of Participants With Adverse Events [From the day of surgical procedure (Day 0) up to 44-days post-surgery]: Percentage of participants with adverse events (including serious and non-serious) were reported. An adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, without judgment about causality. Data is reported for participants with at least one AE. Participants having more than one AE are counted only once in this outcome measure.
• Change From Baseline in Laboratory Parameter: Hemoglobin [From baseline (within 21 days prior to procedure on Day 0) up to hospital discharge (up to 44-days post-surgery on Day 0)]: Change from baseline in laboratory parameter (hemoglobin) was reported.
• Change From Baseline in Laboratory Parameter: Hematocrit [From baseline (within 21 days prior to procedure on Day 0) up to hospital discharge (up to 44-days post-surgery on Day 0)]: Change from baseline in laboratory parameter (hematocrit; expressed as liters of cells per liter of blood) was reported.
• Change From Baseline in Laboratory Parameter: Platelets [From baseline (within 21 days prior to procedure on Day 0) up to hospital discharge (up to 44-days post-surgery on Day 0)]: Change from baseline in laboratory parameter (platelets) was reported.
• Estimated Intraoperative Blood Loss [During surgical procedure on Day 0]: Estimated intraoperative blood loss was reported.
• Number of Participants With Blood Products Transfusion [From the day of surgical procedure (Day 0) up to 44-days post-surgery]: Number of participants with blood products transfusion was reported.

Sex: All, ages: 28 Days to 17 Years, accepts healthy volunteers

Inclusion Criteria:

1. Pediatric subjects aged ≥28 days (≥1 month) to <18 years, requiring non-emergent open hepatic, abdominal, retroperitoneal, pelvic or thoracic (non-cardiac) surgical procedures; i) A minimum of 4 subjects to be enrolled will be aged ≥28 days to <1 year
2. 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 pediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the trial. If the pediatric 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.
3. Presence of an appropriate mild or moderate bleeding soft tissue or hepatic parenchyma Target Bleeding Site (TBS) identified intra-operatively by the surgeon;
4. Ability to firmly press trial treatment at TBS until 4 minutes after TBS identification.

Exclusion Criteria:

1. Subjects with known intolerance to blood products or to one of the components of the study product or is unwilling to receive blood products;
2. Female subjects, of childbearing age (i.e. adolescent), who are pregnant or nursing;
3. Subject is currently participating or plan to participate in any other investigational device or drug study without prior approval from the Sponsor;
4. Subjects who are known, current alcohol and/or drug abusers
5. Subjects admitted for trauma surgery
6. Subjects with any pre or intra-operative findings identified by the surgeon that may preclude conduct of the study procedure
7. Subjects that have received a COVID-19 vaccine either 4 weeks prior to surgery or scheduled to receive COVID-19 vaccine within the 30-day follow-up period
8. Subject with TBS in an actively infected field (Class III Contaminated or Class IV Dirty or Infected)
9. 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 EVARREST to blood flow and pressure during healing and absorption of the product
10. TBS with major arterial bleeding requiring suture or mechanical ligation;
11. Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony confine.

Participant flow

Outcome results

• Absolute Time to Hemostasis (Primary), Median, Minutes: EVARREST Fibrin Sealant Patch 4.00 (4.00 to 4.00)
• Percentage of Participants Who Achieved Hemostatic Success at 4 Minutes (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 77.4 (58.90 to 90.41)
• Percentage of Participants Who Achieved Hemostatic Success at 10 Minutes (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 93.5 (78.58 to 99.21)
• Percentage of Participants With No Re-bleeding at the TBS (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 96.8
• Percentage of Participants With Adverse Events That Were Potentially Related to Bleeding at the TBS (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 5.7
• Percentage of Participants With Adverse Events That Were Potentially Related to Thrombotic Events (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 0
• Percentage of Participants With Re-treatment at the TBS (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 25.7
• Percentage of Participants With Adverse Events (Secondary), Number, Percentage of participants: EVARREST Fibrin Sealant Patch 68.6
• Change From Baseline in Laboratory Parameter: Hemoglobin (Secondary), Mean, Grams per liter (g/L): EVARREST Fibrin Sealant Patch -5.59 +/- 16.353
• Change From Baseline in Laboratory Parameter: Hematocrit (Secondary), Mean, Liters per liter (L/L): EVARREST Fibrin Sealant Patch -0.02 +/- 0.048
• Change From Baseline in Laboratory Parameter: Platelets (Secondary), Mean, 10^9 cells per liter: EVARREST Fibrin Sealant Patch -18.87 +/- 130.724
• Estimated Intraoperative Blood Loss (Secondary), Mean, Milliliters (mL): EVARREST Fibrin Sealant Patch 81.9 +/- 112.00
• Number of Participants With Blood Products Transfusion (Secondary), Count of participants, Participants: EVARREST Fibrin Sealant Patch 11

Adverse events

Time frame: From the day of surgical procedure (Day 0) up to 44-days post-surgery

Serious adverse events by term

Other adverse events by term

9 more terms not shown.

• Study Protocol (PDF, 2023-11-02)
• Statistical Analysis Plan (PDF, 2024-02-27)