A Study Evaluating the Safety and Preliminary Efficacy of sFilm-FS in Controlling Parenchymal Bleeding During Elective Hepatic Surgery

A Phase I/II, Randomized, Prospective, Controlled, Multi-center, Open-label, Two-arm Study Evaluating the Safety and Preliminary Efficacy of sFilm-FS in Controlling Liver Bleeding During Elective Surgery

The Study investigates a new product, sFilm-FS, aimed to help controlling body fluid leakage in general surgery procedures, proposing its use as an adjunct to hemostasis and/or sealing.

Study Overview

• Status: Completed
• Conditions: General Surgery; Hemostasis
• Intervention / Treatment: Combination product: sFilm-FS; Combination product: TACHOSIL®

Detailed Description

Many products have been developed as adjuncts to hemostasis in bleeding situations where traditional methods such as suture, clips or energy-based coagulation are ineffective or impractical.

Many products are not as effective in the presence of active and/or brisk bleeding since the lack of sufficient adhesion strength allows forceful bleeding to simply "float" the products away from the bleeding tissue, prior to the achievement of full hemostasis.

The Study investigates a new product, sFilm-FS, aimed to help the control of body fluid leakage in general surgery procedures, proposing its use as an adjunct to hemostasis and/or sealing.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sara Horn, PhD; Phone Number: +972-733907000; Email: sara@sealantium-med.com
• Study Contact Backup: Name: Orgad Laub, Professor; Phone Number: +972-0544434387; Email: orgad@sealantium-med.com

Study Locations

• Austria
  • Linz, Austria, 4010
    • Ordensklinikum Linz GmbH Barmherzige Schwestern
  • Vienna, Austria, 1090
    • Medical University of Vienna, Department of Surgery Hepatobiliary Unit
• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Center of Ljubljana, Division of Surgery
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63100
      • Washington University in St. Louis, School of Medicine, Department of Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients (males or females) aged ≥ 18 years old.
2. Patients requiring elective open hepatic surgery.
3. Hemoglobin ≥ 8.0 g/dL within 24 hours prior to surgical procedure.
4. Patients understanding the nature of the study and providing their informed consent prior to participation.

5. Patients willing to participate in the study and able to attend the visits and procedures foreseen by study protocol.

   Intra-operative inclusion criteria:

6. Patients with a target bleeding site (TBS) identified by the Investigator during hepatic surgery (intra-operative inclusion criteria).

Exclusion Criteria:

1. Patients having undergone a therapeutic surgical procedure within 30 days from the study enrolment.
2. Patients with a severe coagulopathy defined as INR > 2.0.
3. Patients with platelet count <50,000 x109 PLT/L at the screening.
4. Patients admitted to trauma surgery.
5. Transplant patients due to fulminant hepatic failure.
6. Patients with known or suspected allergy or hypersensitivity to blood products or to one of the components of sFilm-FS or the active-comparator.
7. Patients with anesthesia risk judged to be higher than ASA3 by the Investigator.
8. Patients with at least one of the following concomitant conditions: severe co-morbid conditions known to pose a high risk for surgery and adequate recovery (i.e., liver cirrhosis with Child-Pugh score B or C, cholestasis, heart diseases), immunodeficiency diseases, blood clotting disorders, any conditions known to effect wound healing (i.e., collagen vascular disease), known or current alcohol or drug abusers.
9. Patients suffering from claustrophobia.
10. Patients with implanted or embedded metal objects, prostheses, pacemaker, or fragments in the head or body that would present a risk during the MRI scanning procedure or have worked with ferrous metals either as a vocation or hobby or following trauma (i.e., sheet metal workers, welders, or machinists) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field.
11. Patients being treated with at least one of the following treatments: antibiotic therapy for active infection, fibrin sealants, systemic steroids, or immunosuppressive agents.
12. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.
13. Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for three months later.

14. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception.

    Intra-operative exclusion criteria:

15. Patients identified with a TBS with major arterial bleeding requiring suture or mechanical ligation.
16. Patients identified by the Investigator to have intra-operative bleeding from large defects in large arteries or veins, requiring repair.
17. Patients identified by the Investigator to have intra-operative findings that may preclude conduct of study procedure.
18. Patients having an active local infection in the anatomic surgical area.
19. Patients with occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure.
20. Patients with bleeding site in or near to foramina in bone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sFilm-FS	Combination product: sFilm-FS; sFilm-FS is a sterile bio-compatible bio-absorbable patch embedded with lyophilized powders of Human Fibrinogen, Human Thrombin and calcium chloride.
Active Comparator: TACHOSIL®	Combination product: TACHOSIL®; TACHOSIL® is a fibrin sealant patch composed of an equine collagen patch coated with Human Fibrinogen and Human Thrombin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the evaluation of the incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events AEs related to bleeding at TBS, thrombotic events, transfusion-related complications, post-operative adhesions (MRI assessment)	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the count of participants with abnormal vital signs	Vital signs (considered altogether): blood pressure (mmHg) heart rate (beats/min) temperature (°C) respiratory rate (breaths/min)	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through physical examinations	Physical examination:the detection of the number of patients with clinical abnormalities in different body areas	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the count of participants with abnormal urine analysis values	Urine analysis (considered altogether): specific gravity, pH, glucose, protein, blood, ketones, microscopic examination	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the count of participants with abnormal blood / coagulation parameters profiles	Blood / coagulation parameters profiles (considered altogether): Hb, HC, MCH, MCHC, MCV, RBC, WBC, PLT, Fibrinogen, lactate, D-Dimer, AT, ESR, CRP, BUN, creatinine, uric acid, BIL, LDH, AST (SGOT), ALT (SGPT), Gamma-GT, Na, Ca, P, glucose, albumin, total protein	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the detection of antibodies against fibrin and thrombin	Measurement of plasma levels of antibodies against human fibrinogen and human thrombin	Through study completion, an average of 6 months
To evaluate the safety of sFilm-FS versus the active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques during elective hepatic surgery through the evaluation of the incidence of signs of systemic inflammation	Incidence of signs of systemic inflammation	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure through the proportion of patients achieving hemostasis at TBS	Proportion of patients achieving hemostasis at TBS (absence of bleeding) at 2 (for sFilm-FS product only), 3, 5, 7 or 10 minutes following first product application, without the occurrence of re-bleeding, starting from 10 minutes after product application and until the completion of surgical closure	Day of surgery
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure through the incidence of re-treatment at the TBS	Incidence of re-treatment (one or more additional patch of sFilm-FS or TACHOSIL®) at the TBS at the different time points (2 for sFilm-FS, 3, 5, 7, 10 minutes from first product application)	Day of surgery
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure through time to Hemostasis from first product application	Time to Hemostasis from first product application (TTHP). Time to Hemostasis from patient randomization (TTHR) will be collected as well but will not be used as endpoint	Day of surgery
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure through the percentage of total patients that have achieved hemostasis	Percentage of total patients (patients that achieved hemostasis with a single patch application and patients that required additional patches) that have achieved hemostasis 10 minutes after first product application and therefore did not need to convert to standard of care treatment at the end of these 10 minutes	Day of surgery
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure through incidence of treatment failure	Incidence of treatment failure, based on pre-defined treatment failure criteria (in case the bleeding at TBS (or re-bleeding) is still observed after 10 minutes following first application of study product; if hemostasis at TBS is achieved, but the Investigator decides that an additional treatment is required to ensure the durability of hemostasis; if there is a breakthrough bleeding requiring treatment other than the study product, at any time)	Day of surgery
To preliminarily evaluate the hemostatic efficacy of sFilm-FS in controlling parenchymal bleeding during surgery, related to hemostasis and treatment failure.	Incidence of transfusion requirements in the 6 months follow-up period	From surgery, up to 6 months

Collaborators and Investigators

• Sponsor: Sealantium Medical Ltd.
• Collaborators: Sintesi Research Srl; Home Medics Consulting Ltd.
• Investigators: Study Director: Orgad Laub, Professor, Sealantium Medical Ltd.

Publications and helpful links

General Publications

• Seyednejad H, Imani M, Jamieson T, Seifalian AM. Topical haemostatic agents. Br J Surg. 2008 Oct;95(10):1197-225. doi: 10.1002/bjs.6357.
• Spotnitz WD. Fibrin sealant: past, present, and future: a brief review. World J Surg. 2010 Apr;34(4):632-4. doi: 10.1007/s00268-009-0252-7.
• Vonlanthen R, Slankamenac K, Breitenstein S, Puhan MA, Muller MK, Hahnloser D, Hauri D, Graf R, Clavien PA. The impact of complications on costs of major surgical procedures: a cost analysis of 1200 patients. Ann Surg. 2011 Dec;254(6):907-13. doi: 10.1097/SLA.0b013e31821d4a43.
• Spotnitz WD, Burks S. Hemostats, sealants, and adhesives: components of the surgical toolbox. Transfusion. 2008 Jul;48(7):1502-16. doi: 10.1111/j.1537-2995.2008.01703.x. Epub 2008 Apr 14.
• Sundaram CP, Keenan AC. Evolution of hemostatic agents in surgical practice. Indian J Urol. 2010 Jul;26(3):374-8. doi: 10.4103/0970-1591.70574.
• Fok M, Ah-Chong AK, Cheng SW, Wong J. Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. Br J Surg. 1991 Mar;78(3):342-5. doi: 10.1002/bjs.1800780323.
• Scherock TR, Clifford MD, Deveney W, Eneglebert J, Dunphy MD, Factors contributing to leakage of colonic anastomoses, Annual meeting of the Southern Surgical Association Boca Raton, Florida, 1972
• Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood. 2005 Oct 15;106(8):2605-12. doi: 10.1182/blood-2005-04-1710. Epub 2005 Jun 30.
• Tanaka KA, Taketomi T, Szlam F, Calatzis A, Levy JH. Improved clot formation by combined administration of activated factor VII (NovoSeven) and fibrinogen (Haemocomplettan P). Anesth Analg. 2008 Mar;106(3):732-8, table of contents. doi: 10.1213/ane.0b013e318163fc76.
• Wheat JC, Wolf JS Jr. Advances in bioadhesives, tissue sealants, and hemostatic agents. Urol Clin North Am. 2009 May;36(2):265-75, x. doi: 10.1016/j.ucl.2009.02.002.
• Hung A, Garcia-Tsao G. Acute kidney injury, but not sepsis, is associated with higher procedure-related bleeding in patients with decompensated cirrhosis. Liver Int. 2018 Aug;38(8):1437-1441. doi: 10.1111/liv.13712. Epub 2018 Feb 24.
• Randall D, Fenner J, Gillott R, Ten Broek R, Strik C, Spencer P, Bardhan KD. A Novel Diagnostic Aid for Detection of Intra-Abdominal Adhesions to the Anterior Abdominal Wall Using Dynamic Magnetic Resonance Imaging. Gastroenterol Res Pract. 2016;2016:2523768. doi: 10.1155/2016/2523768. Epub 2016 Jan 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Liver; Coagulation; Fibrin sealant; Hepatic surgery; Body fluid leakage; Parenchymal bleeding; Fibrin patch; Human Fibrinogen; Human Thrombin
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: HEM-01-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No