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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hemostasis, General Surgery

Intervention / Treatment
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* Combination Product: sFilm-FS
* Combination Product: TACHOSIL®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (males or females) aged ≥ 18 years old. Patients requiring elective open hepatic surgery. Hemoglobin ≥ 8.0 g/dL within 24 hours prior to surgical procedure. Patients understanding the nature of the study and providing their informed consent prior to participation. Patients willing to participate in the study and able to attend the visits and procedures foreseen by study protocol. Patients with a target bleeding site (TBS) identified by the Investigator during hepatic surgery (intra-operative inclusion criteria). Exclusion Criteria: Patients undergoing a re-operative procedure. Patients having undergone a therapeutic surgical procedure within 30 days from the study enrolment. Patients with a severe coagulopathy defined as INR > 2.0. Patients with platelet count <50,000 x109 PLT/L at the screening (ref. 11). Patients admitted to trauma surgery. Transplant patients due to fulminant hepatic failure. Patients with known or suspected allergy or hypersensitivity to blood products or to one of the components of sFilm-FS or the active-comparator. Patients with anesthesia risk judged to be higher than ASA3 by the Investigator. 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. Patients being treated with at least one of the following treatments: antibiotic therapy for active infection, fibrin sealants, systemic steroids or immunosuppressive agents. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment. 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. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception. Intra-operative exclusion criteria: Patients identified with a TBS with major arterial bleeding requiring suture or mechanical ligation. Patients identified by the Investigator to have intra-operative bleeding from large defects in large arteries or veins, requiring repair. Patients identified by the Investigator to have intra-operative findings that may preclude conduct of study procedure. Patients having an active local infection in the anatomic surgical area. Patients with occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure. Patients with bleeding site in or near to foramina in bone.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body fluid leakage, Liver, Parenchymal bleeding, Hepatic surgery, Fibrin sealant, Fibrin patch, Human Fibrinogen, Human Thrombin, Coagulation