Adjunctive Application of BioFoam Surgical Matrix in Liver Surgery

• BioFoam Surgical Matrix (Device), also known as BioFoam: Surgical adjunct to control bleeding in open liver surgery
• Gelfoam Plus (Device), also known as Gelfoam with thrombin: Surgical adjunct in control of bleeding in open liver surgery

Primary outcomes

• Time to Achieve Intraoperative Hemostasis Following Open Liver Resection Surgery in Subjects Receiving an Application of BioFoam or a Standard Topical Hemostatic Agent [3 minutes following a single application of the prescribed hemostatic agent]: Number of subjects achieving intraoperative hemostasis (y/n) at 3 minutes following a single application of the prescribed hemostatic agent

Secondary outcomes

• Time to Hemostasis [1, 3, 5, 7, and 10 minutes following application of prescribed hemostatic agent]: Number of subjects achieving hemostasis \[by assessing for hemostasis (yes/no)\] at pre-determined time points: 1, 3, 5, 7, and 10 minutes following application of prescribed hemostatic agent. Time to hemostasis is recorded as the first of the predetermined time points to receive a "yes" assessment.
• Achievement of Immediate Hemostasis [1 minute after application of prescribed hemostatic agent]: Number of subjects achieving hemostasis at 1 minute after application of prescribed hemostatic agent
• Intraoperative Blood Loss [Time from initial application to confirmed achievement of hemostasis (eval. up to 10 minutes following application of hemostatic agent)]: Amount of blood lost between time of initial application of prescribed hemostatic agent and confirmed achievement of hemostasis (achievement of hemostasis eval. out to 10 minutes following application of prescribed hemostatic agent)
• Amount of Postoperative Bilious Drainage [Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively]
• Amount of Postoperative Fluid Loss [Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively]: Amount of fluid lost postoperatively \[measured between time of drain insertion (if applicable) to drain removal, average 24-72 hours postoperatively\]
• Duration of Drainage [Time between drain insertion and last recorded emptying time during hospitalization (where applicable), average 24-72 hours postoperatively]: Total length of time between drain insertion and last recorded emptying time during hospitalization (where applicable), average 24-72 hours postoperatively
• Amount of Intraoperative Blood Products Administered [Intraoperatively (throughout procedure, from initial skin cut to final wound closure, average 4-5 hours duration)]: Amount of blood products administered intraoperatively (throughout procedure: from initial skin cut to final wound closure)
• Subject Laboratory Evaluations [Preoperatively through final 2 year follow-up]: Number of laboratory evaluations outside of range from preoperative assessments through final 2 year follow-up
• Eval. for Presence of Device by MRI w/ & w/Out Contrast, & Diagnose/Eval. Abdominal Fluid Collection/Biliary Leak, Residual Scarring, Hepatic Regeneration, & Assess for Emergence of Primary/Recurrent Malignancy by MRI w/ or w/Out Contrast as Appropriate [Within 48 hours postoperatively, up to 48 hours prior to hospital discharge (avg. 5-7 days postoperatively), and 30 days, 3 months, 6 months, 9 months, 1 year, and 2 years postoperatively]
• Number of Subjects Requiring Reoperation Due to Bleeding and/or Biliary Leakage (Reoperation Required? y/n) [After final wound closure through 2 year follow-up visit (average 2 yr duration)]: Number of subjects requiring reoperation due to bleeding and/or biliary leakage out to 2 years postoperatively (reoperation required? y/n)
• Total Time of Operative Procedure [Skin cut to skin closure (average 4-5 hour duration)]
• Core Body Temperature [At the time of test or control article application (expected average 3-4 hours from skin cut)]
• Total Hospitalization Time [Hospital admission (day of surgery) until hospital discharge (average 5-7 days)]: Length of time between hospital admission (day of surgery) and hospital discharge (average 5-7 days)
• Subjects Requiring Additional Hospitalization/Surgical Intervention [Any hospitalization/surgical intervention following final wound closure through 2 year follow-up visit (average 2 yr duration)]: Number of subjects requiring additional hospitalization/surgical intervention following final wound closure through the 2 year follow-up
• Evaluation of Anti-Bovine Serum Albumin (Anti-BSA) Antibody Titers [Preoperatively (up to 30 days before surgery), immediately post-application of hemostatic agent (within minutes), within 48 hrs postoperatively, up to 48 hrs before hospital discharge, at 7-10 days, 30 days, 3 mos, 6 mos, 9 mos, 1 yr, and 2 yr postop]: Evaluation of anti-BSA antibody titers to determine number of subjects/participants with a positive titer at various time points
• Number of Procedure Complications and/or Adverse Events [Through final follow-up (2 years postoperatively)]

Sex: All, ages: 18 Years to any

Preoperative Inclusion Criteria:

* Subject is undergoing an elective liver resection procedure that requires treatment of the exposed parenchymal surface due to the intraoperative presence of blood following ligature of vessels visible with the unaided eye;
* Subject has adequate hepatic function as indicated by a Model for End-Stage Liver Disease (MELD) score of <10 at ≤30 days and at ≤7 days prior to surgery;
* Subject has adequate hemostatic function identified as an international normalized ratio (INR), platelet count, and activated clotting time within the central laboratory's normal reference range;
* Subject or an authorized legal representative is willing and able to give prior written informed consent for investigation participation; and
* Subject is ≥ 18 years of age.

Preoperative Exclusion Criteria:

* Subject with known or suspected sensitivity to products of bovine origin
* Subject with known or suspected sensitivity to glutaraldehyde
* Subject with active infection (either systemic or in the treatment region) or hepatic cysts due to parasitic disease and/or abscesses due to bacterial and/or amebic disease;
* Subject with abnormal calcium metabolism identified as values for ionized calcium and serum calcium corrected for serum albumin that are outside of the central laboratory's normal reference range;
* Subject with abnormal renal status identified as an estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), serum creatinine, sodium, chloride, potassium, and/or bicarbonate values that are outside of the central laboratory's normal reference range;
* Subject with hyperparathyroidism identified as an intact parathyroid hormone level >72 pg/mL, serum calcium >10.6 mg/dL, and phosphate <2.4 mg/dL, and, for secondary or tertiary hyperparathyroidism only, alkaline phosphatase >147 U/L
* Subject with a pancreatic amylase and/or lipase value outside of the central laboratory's normal reference range;
* Subject with blunt and/or penetrating liver trauma;
* Subject diagnosed with any coagulation disorder;
* Subject whose life-expectancy is less than that required for the prescribed follow-up duration;
* Subject who has been treated with an investigational product and has not completed the entire follow-up period for that investigational product;
* Subject with any surgical implant that would interfere with necessary follow-up imaging;
* Subject who is pregnant (as confirmed by a urine pregnancy test), planning on becoming pregnant during the follow-up period, or actively breast-feeding;
* Subject who is undergoing concomitant procedures other than (1) cholecystectomy, (2) umbilical hernia repair, or (3) uncomplicated colon resection (i.e., no significant spillage);
* Subject who is immunocompromised;
* Subject with an American Society of Anesthesiologist (ASA) Score >2
* Subject with a MELD score of ≥10 at ≤30 days or at ≤7 days prior to surgery;
* Subject diagnosed with an autoimmune disease; and
* Subject in whom the surgeon intends to use adhesion prevention products.
* Subject who is returning to the operating room (OR) to address a complication associated with a liver resection, including but not limited to hematoma evacuation and biliary leak.

Intraoperative Inclusion Criterion:

\- Subject in whom bleeding (assignment of a "Bleeding Score" of 1 or 2) from the exposed parenchymal surface after ligature of vessels visible with the unaided eye and removal of any clamps used for hemostasis is observed

Intraoperative Exclusion Criterion:

\- Subject in whom any major intraoperative bleeding incidences during the resection procedure occurred (i.e., subject with assignment of an American College of Surgeons Advanced Trauma Life Support Hemorrhage Class of II, III, or IV Hemorrhage)

Participant flow

Outcome results

• Time to Achieve Intraoperative Hemostasis Following Open Liver Resection Surgery in Subjects Receiving an Application of BioFoam or a Standard Topical Hemostatic Agent (Primary), Number, participants: Control Bleeding in BioFoam Subjects/Participants ; Control Bleeding in Gelfoam Plus Subjects/Participants 1
• Time to Hemostasis (Secondary), Number, minutes: Subjects/Participants Receiving BioFoam ; Subjects/Participants Receiving Gelfoam Plus 1
• Achievement of Immediate Hemostasis (Secondary), Number, participants: Achieve Immediate Hemostasis in BioFoam Subjects/Participants ; Achievement of Immediate Hemostasis in Gelfoam Plus Subjects 1
• Intraoperative Blood Loss (Secondary)
• Amount of Postoperative Bilious Drainage (Secondary), Number, milliliters (mL): BioFoam Surgical Matrix ; Gelfoam Plus NA
• Amount of Postoperative Fluid Loss (Secondary), Number, milliliters (mL): BioFoam Surgical Matrix ; Gelfoam Plus NA
• Duration of Drainage (Secondary), Number, hours: Duration of Postoperative Drainage in BioFoam Subjects ; Duration of Postoperative Drainage in Gelfoam Plus Subjects NA
• Amount of Intraoperative Blood Products Administered (Secondary), Number, units of blood product(s): Amt. of Intraop. Blood Products Rec'd by BioFoam Subjects ; Amt. of Intraop. Blood Products Rec'd by Gelfoam Plus Subjects NA
• Subject Laboratory Evaluations (Secondary), Number, Number of participants with labs in rang: Laboratory Evaluations for BioFoam Subjects Out of Range ; Laboratory Evaluations for Gelfoam Plus Subjects Out of Range NA
• Eval. for Presence of Device by MRI w/ & w/Out Contrast, & Diagnose/Eval. Abdominal Fluid Collection/Biliary Leak, Residual Scarring, Hepatic Regeneration, & Assess for Emergence of Primary/Recurrent Malignancy by MRI w/ or w/Out Contrast as Appropriate (Secondary), Number, participants: Presence of Device Via MRI in BioFoam Surgical Matrix Subjects ; Presence of Device Via MRI in Gelfoam Plus Subjects 1
• Number of Subjects Requiring Reoperation Due to Bleeding and/or Biliary Leakage (Reoperation Required? y/n) (Secondary), Number, number of participants: BioFoam Subj. Requiring Reop. Due to Bleeding/Biliary Leakage ; Gelfoam Plus Subj. Requiring Reop. Due to Bleeding/Bili. Leak 0
• Total Time of Operative Procedure (Secondary), Number, minutes: Total Time of Procedure for BioFoam Surgical Matrix Subjects ; Total Time of Procedure for Gelfoam Plus Subjects 300
• Core Body Temperature (Secondary), Number, degrees Celcius: Core Body Temp of BioFoam Subjects During Hemostat Application ; Core Body Temp of Gelfoam Plus During Hemostat Application 36.5
• Total Hospitalization Time (Secondary), Number, days: Length of Hospital Stay for BioFoam Surgical Matrix Subjects ; Length of Hospital Stay for Gelfoam Plus Subjects NA
• Subjects Requiring Additional Hospitalization/Surgical Intervention (Secondary), Number, # of participants: # of BioFoam Subjects Requiring Hospitalization/Intervention ; # of Gelfoam Plus Subj. Requiring Hospitalization/Intervention NA
• Evaluation of Anti-Bovine Serum Albumin (Anti-BSA) Antibody Titers (Secondary)
• Number of Procedure Complications and/or Adverse Events (Secondary), Number, Number of complications and AEs: Complications/Adverse Events in Subjects Receiving BioFoam ; Complications/Adverse Events in Subj. Receiving Gelfoam Plus 31

Adverse events

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Early termination leading to small number of subjects evaluated (n=1).

• Scott B Capps, MS, Study director, CryoLife, Inc.