Adjunctive Application of BioFoam Surgical Matrix in Liver Surgery

Phase 3TerminatedNCT01458561

CryoLife, Inc.1 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Intraoperative Bleeding

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

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

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

Secondary Outcomes

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

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

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)

Amount of Postoperative Bilious Drainage

Time frame: Time from drain insertion to drain removal (where applicable), average 24-72 hours postoperatively

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

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

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)

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

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

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)

Total Time of Operative Procedure

Time frame: Skin cut to skin closure (average 4-5 hour duration)

Core Body Temperature

Time frame: At the time of test or control article application (expected average 3-4 hours from skin cut)

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)

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)

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

Number of Procedure Complications and/or Adverse Events

Time frame: Through final follow-up (2 years postoperatively)