Clinical trial NCT01458561: Adjunctive Application of BioFoam Surgical Matrix in Liver Surgery
Official title: An Investigational Plan Evaluating the Operative Management of Parenchymal Bleeding By Means of an Adjunctive Application of BioFoam Surgical Matrix in Liver Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Intraoperative Bleeding
Keywords: Hemostatic agent
Liver surgery
Hemostasis
Lead sponsor: CryoLife
Sponsor class: UNKNOWN
Collaborators: name: United States Department of Defense
First posted: 2011-10-25
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Time to Achieve Intraoperative Hemostasis Following Open Liver Resection Surgery in Subjects Receiving an Application of BioFoam or a Standard Topical Hemostatic Agent
timeFrame: 3 minutes following a single application of the prescribed hemostatic agent
Secondary outcomes:
measure: Time to Hemostasis
timeFrame: 1, 3, 5, 7, and 10 minutes following application of prescribed hemostatic agent
measure: Achievement of Immediate Hemostasis
timeFrame: 1 minute after application of prescribed hemostatic agent
measure: Intraoperative Blood Loss
timeFrame: Time from initial application to confirmed achievement of hemostasis (eval. up to 10 minutes following application of hemostatic agent)
measure: Amount of Postoperative Bilious Drainage
timeFrame: Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively
measure: Amount of Postoperative Fluid Loss
timeFrame: Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively
measure: Duration of Drainage
timeFrame: Time between drain insertion and last recorded emptying time during hospitalization (where applicable), average 24-72 hours postoperatively
measure: Amount of Intraoperative Blood Products Administered
timeFrame: Intraoperatively (throughout procedure, from initial skin cut to final wound closure, average 4-5 hours duration)
measure: Subject Laboratory Evaluations
timeFrame: Preoperatively through final 2 year follow-up
measure: 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
timeFrame: 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
measure: Number of Subjects Requiring Reoperation Due to Bleeding and/or Biliary Leakage (Reoperation Required? y/n)
timeFrame: After final wound closure through 2 year follow-up visit (average 2 yr duration)
measure: Total Time of Operative Procedure
timeFrame: Skin cut to skin closure (average 4-5 hour duration)
measure: Core Body Temperature
timeFrame: At the time of test or control article application (expected average 3-4 hours from skin cut)
measure: Total Hospitalization Time
timeFrame: Hospital admission (day of surgery) until hospital discharge (average 5-7 days)
measure: Subjects Requiring Additional Hospitalization/Surgical Intervention
timeFrame: Any hospitalization/surgical intervention following final wound closure through 2 year follow-up visit (average 2 yr duration)
measure: Evaluation of Anti-Bovine Serum Albumin (Anti-BSA) Antibody Titers
timeFrame: 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
measure: Number of Procedure Complications and/or Adverse Events
timeFrame: Through final follow-up (2 years postoperatively)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: CryoLife, Inc.
name: Scott B Capps, MS
role: STUDY_DIRECTOR
References: