Intraoperative Bleeding
Conditions
Keywords
Hemostatic agent, Liver surgery, Hemostasis
Brief summary
This is a prospective, multicenter, randomized, controlled investigation. Subjects in which bleeding from the exposed parenchymal surface is observed intraoperatively following the ligature of vessels visible with the unaided eye will be randomized to an adjunctive application of BioFoam or a standard topical hemostatic agent (Gelfoam with thrombin, in the form of Gelfoam Plus) to the entire exposed parenchymal surface. Following primary treatment of the exposed parenchymal surface as prescribed by the randomization scheme, treatment sites will be visually evaluated for the continued presence of bleeding. The overall objective of this investigation is to collect clinical data concerning the safety and effectiveness of BioFoam used as an adjunct to conservative measures of achieving hemostasis, such as manual pressure, cautery, and ligation, for intraoperative capillary, arteriolar, and venular bleeding (5 second stack of 5 gauze surface Bleeding Score = 1b or 2, score to be validated) on newly resected liver parenchyma in hemodynamically stable (American College of Surgeons' Advanced Trauma Life Support Class I Hemorrhage) and non-coagulopathic patients in the open treatment of exposed liver parenchyma versus a standard topical hemostatic agent, Gelfoam Plus. It is not intended for traumatic liver injury. The investigation will be conducted at a maximum of three investigational sites.
Interventions
DEVICEBioFoam Surgical Matrix
Surgical adjunct to control bleeding in open liver surgery
DEVICEGelfoam Plus
Surgical adjunct in control of bleeding in open liver surgery
Sponsors
United States Department of Defense
CryoLife, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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) |
| 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) | — |
| 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 | — |
Countries
United States
Participant flow
Recruitment details
Recruitment was limited to potential subjects who were being seen by a liver surgeon because they required a liver resection procedure. The first site was cleared to begin recruitment on October 20, 2010 and recruitment was closed on August 31, 2012 when all investigators were formally notified of the decision to terminate the study.
Pre-assignment details
All potential subjects were required to meet preoperative and operative screening criteria in order to be enrolled into the investigation and assigned to a treatment group.
Participants by arm
| Arm | Count |
|---|---|
| BioFoam Surgical Matrix Control of bleeding using BioFoam Surgical Matrix as a surgical adjunct
BioFoam Surgical Matrix : Surgical adjunct to control bleeding in open liver surgery | 0 |
| Gelfoam Plus Control of bleeding using Gelfoam Plus as a surgical adjunct
Gelfoam Plus : Surgical adjunct in control of bleeding in open liver surgery | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Total | Gelfoam Plus |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 1 participants | 1 participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 0 | 57 years STANDARD_DEVIATION 0 |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 1 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 1 / 1 |
| serious Total, serious adverse events | 0 / 0 | 1 / 1 |
Outcome results
Primary
Time to Achieve Intraoperative Hemostasis Following Open Liver Resection Surgery in Subjects Receiving an Application of BioFoam or a Standard Topical Hemostatic Agent
Number of subjects achieving intraoperative hemostasis (y/n) at 3 minutes following a single application of the prescribed hemostatic agent
Time frame: 3 minutes following a single application of the prescribed hemostatic agent
Population: Study was terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Time to Achieve Intraoperative Hemostasis Following Open Liver Resection Surgery in Subjects Receiving an Application of BioFoam or a Standard Topical Hemostatic Agent | 1 participants |
Secondary
Achievement of Immediate Hemostasis
Number of subjects achieving hemostasis at 1 minute after application of prescribed hemostatic agent
Time frame: 1 minute after application of prescribed hemostatic agent
Population: Study was terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Achievement of Immediate Hemostasis | 1 participants |
Secondary
Amount of Intraoperative Blood Products Administered
Amount of blood products administered intraoperatively (throughout procedure: from initial skin cut to final wound closure)
Time frame: Intraoperatively (throughout procedure, from initial skin cut to final wound closure, average 4-5 hours duration)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Amount of Intraoperative Blood Products Administered | NA units of blood product(s) |
Secondary
Amount of Postoperative Bilious Drainage
Time frame: Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Amount of Postoperative Bilious Drainage | NA milliliters (mL) |
Secondary
Amount of Postoperative Fluid Loss
Amount of fluid lost postoperatively \[measured between time of drain insertion (if applicable) to drain removal, average 24-72 hours postoperatively\]
Time frame: Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Amount of Postoperative Fluid Loss | NA milliliters (mL) |
Secondary
Core Body Temperature
Time frame: At the time of test or control article application (expected average 3-4 hours from skin cut)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Core Body Temperature | 36.5 degrees Celcius |
Secondary
Duration of Drainage
Total length of time between drain insertion and last recorded emptying time during hospitalization (where applicable), average 24-72 hours postoperatively
Time frame: Time between drain insertion and last recorded emptying time during hospitalization (where applicable), average 24-72 hours postoperatively
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Duration of Drainage | NA hours |
Secondary
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
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | 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 | 1 participants |
Secondary
Evaluation of Anti-Bovine Serum Albumin (Anti-BSA) Antibody Titers
Evaluation of anti-BSA antibody titers to determine number of subjects/participants with a positive titer at various time points
Time frame: 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
Population: Blood samples were to be analyzed in batches to more accurately assess for any changes over time; the study was terminated before the first batch was analyzed, so no data is available for anti-BSA titer testing.
Secondary
Intraoperative Blood Loss
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)
Time frame: Time from initial application to confirmed achievement of hemostasis (eval. up to 10 minutes following application of hemostatic agent)
Population: Study terminated before appropriate data collection/analysis
Secondary
Number of Procedure Complications and/or Adverse Events
Time frame: Through final follow-up (2 years postoperatively)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Number of Procedure Complications and/or Adverse Events | 31 Number of complications and AEs |
Secondary
Number of Subjects Requiring Reoperation Due to Bleeding and/or Biliary Leakage (Reoperation Required? y/n)
Number of subjects requiring reoperation due to bleeding and/or biliary leakage out to 2 years postoperatively (reoperation required? y/n)
Time frame: After final wound closure through 2 year follow-up visit (average 2 yr duration)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Number of Subjects Requiring Reoperation Due to Bleeding and/or Biliary Leakage (Reoperation Required? y/n) | 0 number of participants |
Secondary
Subject Laboratory Evaluations
Number of laboratory evaluations outside of range from preoperative assessments through final 2 year follow-up
Time frame: Preoperatively through final 2 year follow-up
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Subject Laboratory Evaluations | NA Number of participants with labs in rang |
Secondary
Subjects Requiring Additional Hospitalization/Surgical Intervention
Number of subjects requiring additional hospitalization/surgical intervention following final wound closure through the 2 year follow-up
Time frame: Any hospitalization/surgical intervention following final wound closure through 2 year follow-up visit (average 2 yr duration)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Subjects Requiring Additional Hospitalization/Surgical Intervention | NA # of participants |
Secondary
Time to Hemostasis
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.
Time frame: 1, 3, 5, 7, and 10 minutes following application of prescribed hemostatic agent
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Time to Hemostasis | 1 minutes |
Secondary
Total Hospitalization Time
Length of time between hospital admission (day of surgery) and hospital discharge (average 5-7 days)
Time frame: Hospital admission (day of surgery) until hospital discharge (average 5-7 days)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Total Hospitalization Time | NA days |
Secondary
Total Time of Operative Procedure
Time frame: Skin cut to skin closure (average 4-5 hour duration)
Population: Study terminated before any subjects were enrolled into the BioFoam arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Bleeding in Gelfoam Plus Subjects/Participants | Total Time of Operative Procedure | 300 minutes |