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
Phase: PHASE1
Conditions: Hemostasis, General Surgery
Sponsor: Sealantium Medical Ltd.

Study Protocol No: HEM-01-17                   CONFIDENTIAL                     Version: 5.0 of 8th July 2021 
 
 
 
 
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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.= 
 
 
 
 
 
Study Protocol No:   
HEM-01-17 
 
EudraCT No:   
 
2018-000434-34 
 
Clinical Phase:  
 
Phase I / II 
 
Protocol Version and Date: 
5.0 dated 8th July, 2021 
 
Replaces Version: 
 
3.0 dated 19th May, 2021 
 
Principal Investigator: 
Prof. Grant V. Bochicchio 
Harry Edison Professor of Surgery 
Chief of Acute and Critical Care Surgery 
Washington University School of Medicine 
Barnes Jewish Hospital Plaza 
St. Louis, MO 63100, U.S.A. 
  
 
 
 
Sponsor:     
 
 
Sealantium Medical Ltd. 
 
 
 
 
 
Ha'Amal 11 St.  
 
 
 
 
 
Rosh Ha'Ayin, Israel 
 
 
 
 
 
 
 
This clinical study will be conducted in accordance with the Sponsor’s and Sintesi Research’s 
Standard Operating Procedures (SOPs), current Good Clinical Practice (GCP), the provisions of 
ICH (International Conference on Harmonization), EU Directives (for sites based in the European 
Community) and Code of Federal Regulation (for sites based in the U.S.A.).  
 
 
CONFIDENTIAL 
The information contained in this document is proprietary and private and will not be 
disclosed to others than the Investigator(s) and his/her/their staff, applicable IRB(s)/IEC(s) 
and RA(s)/CA(s) without prior written approval except to the extent necessary to obtain 
informed consent from those persons to whom the medication may be administered. 
 

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Revision History & Summary of changes 
Version 
Description of change 
Reason for change 
1.0 of 
18/09/18 
First issue 
--- 
2.0 of 
10/04/19 
Various updates, clarifications, and alignments 
with regulatory requirements   
IND Immediate Requests 
from FDA 
3.0 of 
19/05/21 
Various updates & clarifications, modification 
of sample size, inclusion of U.S. site   
Sponsor’s Decision 
5.0 of 
08/07/21 
Removal of TEG testing and related exclusion 
criteria 
 
Varius updated, clarifications, and alignments 
with regulatory requirements 
Sponsor’s Decision 
 
IND Immediate Requests 
from FDA 
 
 

Study Protocol No: HEM-01-17                   CONFIDENTIAL                     Version: 5.0 of 8th July 2021 
 
 
 
 
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INVESTIGATOR’S STATEMENT 
 
 
Study Title:  <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= 
 
 
1. Obtain Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approval 
of study protocol, Patient Informed Consent Form, any amendment(s) to the study protocol 
and yearly re-approval as required. 
2. Obtain written informed consent from each participant or his/her legal representative, prior 
of the enrolment of the patient in the study, using the approved patient Informed Consent 
Form. 
3. Conduct the study in strict accordance with this protocol, the Declaration of Helsinki, the 
current GCP guidelines, the laws and regulations of the countries involved in the Study, 
insurance requirements and will attempt to complete the study within the designated time. 
4. Report any Serious Adverse Events to the Sponsor  within 24 hours. 
5. Keep the IRB/IEC informed of adverse events and report status of the study as required. 
6. Keep records on all patients’ information (eCRF, IP shipment and return forms and all 
other information collected throughout the study) according to the requirements specified 
in the Study agreement. 
7. Assure access to patients' medical records to the Sponsor or to its designated 
representative(s). 
8. Maintain confidentiality of all information received or developed in connection with this 
protocol. 
9. Comply with EU Directives (for sites based in the European Community) and Code of 
Federal Regulation (for sites based in the U.S.A.) regarding the conduct of the trial, as 
applicable. 
 
I have received and read the Investigator’s Brochure for sFilm-FS, I have read the HEM-01-17 
protocol and agree to conduct the study as outlined.  I agree to maintain the confidentiality of all 
information received or developed in connection with this protocol. 
 
 
 
Principal Investigator’s Name:  
__________________________________ 
 
 
Signature:  
 
 
 
__________________________________ 
 
 
Date:   
 
 
 
__________________________________ 
 
 
Institution:  
 
 
 
__________________________________ 

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1. STUDY SYNOPSIS 
Study Title 
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 
Study Code 
HEM-01-17 
EudraCT N. 
2018-000434-34 
Clinical Phase 
Phase I / II 
Study 
Objectives 
The primary objective of this study is to evaluate the safety of sFilm-FS 
versus an active-comparator (TACHOSIL®) when used as adjunct to 
conventional hemostatic techniques during elective liver surgery.  
The secondary objective of this study is to preliminarily evaluate the 
hemostatic efficacy of sFilm-FS in controlling liver bleeding during 
elective surgery. 
Study Design 
This is a randomized, prospective, controlled, multi-center, open-label, 
two-arms study evaluating the safety and preliminary efficacy of  
sFilm-FS in controlling liver bleeding during elective surgery.  
Patients will be randomized with a 1:1 allocation ratio to either  
sFilm-FS (investigational product) or TACHOSIL® (active-comparator).  
All patients will be followed post-operatively through discharge and up 
to 6 months post-surgery, following the Schedule of Assessments 
provided below. 
A Data Safety Monitoring Board (DSMB) will be established and have 
responsibility for the review of data and identification of any potential 
safety issues throughout the study. If necessary, the DSMB will make 
recommendations regarding protocol revisions and will recommend 
whether the study should proceed based on the safety data considering 
established stopping rules.   
Study 
Procedure 
The surgical procedure will be performed as per standard of care at the 
investigational site. A target bleeding site (TBS) will be identified  
intra-operatively by the Investigator when liver bleeding is encountered 
during surgery and conventional methods of bleeding control are 
ineffective.   
Target Bleeding Site (TBS) is defined as the first bleeding site in which 
conventional methods of bleeding control (i.e., suture, ligature, cautery) 
are ineffective or impractical. The TBS must be a site where occlusion of 
the injured surface blood vessels is required to achieve hemostasis. It must 
be possible to cover the TBS adequately, with an appropriate overlap, 
using a single unit of product (sFilm-FS or TACHOSIL®). This excludes 
bleeding from large defects in large arteries or veins requiring repair. 
Once the TBS has been identified, the Investigator will immediately 
enroll and randomize the patient into one of the following treatment arms, 
according to a pre-determined randomization scheme:  

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• Group A (investigational product): sFilm-FS will be applied at the 
target bleeding site immediately after conventional methods of control 
have been exhausted. The sFilm-FS should cover adequately the 
entire TBS. Following application of sFilm-FS, the Investigator will 
immediately apply manual compression continuously for at least 2 
minutes. A surgical sponge may be used to assist in providing 
adequate pressure. Hemostasis will be assessed after carefully 
releasing the compression at the site. sFilm-FS should not be removed 
once bleeding has stopped. A maximum of 4 units of sFilm-FS may 
be used per patient. 
 
• Group B (active comparator): TACHOSIL® will be applied at the 
target bleeding site immediately after conventional methods of control 
have been exhausted. TACHOSIL® should be applied as per the 
approved prescribing information, with manual compression for at 
least 3 minutes. A maximum of 4 units of TACHOSIL® may be used 
per patient. 
 
If additional bleeding sites/regions requiring a topical hemostatic product 
are identified after the treatment of the initial target bleeding site, these 
bleeding sites should be treated with the same study treatment according 
to the patient’s randomization assignment, if clinically appropriate. These 
areas will not be assessed for hemostasis, but information will be 
recorded. 
Investigational 
Product 
sFilm-FS is a sterile bio-compatible bio-absorbable patch which consists 
of a polymeric film composed of a tri-block polymer (device component) 
containing Polyethylene Glycol (PEG) Poly-Caprolactone (PCL) and 
Poly-Lactide Acid (PLA), embedded with lyophilized powders of Human 
Fibrinogen, Human Thrombin (biological components) and calcium 
chloride. sFilm-FS is supplied ready to use in the patch size of 5 x 5 cm 
(~ 2 x 2 inch).  
Comparator 
Product 
TACHOSIL® is a fibrin sealant patch composed of an equine collagen 
patch coated with Human Fibrinogen and Human Thrombin. The product 
is ready for use and for the study it will be supplied in patch size of 4.8 x 
4.8 cm (1.9 x 1.9 inch).  
Study 
Population 
Patients undergoing elective, open abdominal surgery in which liver  
bleeding is expected, with presence of an appropriate target bleeding site 
(TBS) identified intra-operatively by the Investigator. 30 completed 
patients are to be enrolled in this study. 

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Inclusion 
Criteria 
 
 
1. Patients (males or females) aged ≥ 18 years old. 
2. Patients requiring elective surgery in which liver bleeding will be 
encountered. 
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 surgery in which liver bleeding will be 
encountered. 
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 (ref. 
11). 
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. * 
 

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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. 
 
* Adequate contraceptive methods may include any approved method of 
birth control such as combined estrogen and progestogen containing 
hormonal contraception, associated with inhibition of ovulation (oral, 
intravaginal, transdermal), progestogen-only hormonal contraception 
associated with inhibition of ovulation (oral, injectable, implantable), 
intra-uterine devices, condoms, abstinence or vasectomized partner. 
Contraception should be maintained until study end. 
Primary 
Endpoint 
The primary endpoint of the study is the evaluation of safety. Safety will 
be assessed from randomization of patients until the last follow-up visit 
and will include evaluation of treatment emergent adverse events. In 
particular, patients will be followed for AEs related to bleeding at TBS, 
thrombotic events, transfusion-related complications, post-operative 
adhesions (MRI assessment) as well as vital signs, physical examination, 
urine analysis, blood / coagulation parameters profiles, antibodies against 
fibrinogen and thrombin, and signs of systemic inflammation. 
Secondary 
Endpoints 
The secondary endpoints of the study are related to product hemostatic 
efficacy. For this purpose, hemostasis and treatment failure are defined. 
Hemostasis is defined as an absence/cessation of bleeding at the target 
bleeding site (TBS) according to the surgeon’s judgement, so that the 
surgical closure of the field could be started.  
Treatment failure is defined as follows: 
- 
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 

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Secondary 
Endpoints 
 Secondary endpoints include: 
• Proportion of patients achieving hemostasis at TBS at 2 (applicable 
only for sFilm-FS), 3, 5, 7 or 10 minutes following first product 
application, without the occurrence of re-bleeding, starting from10 
minutes from first product application and until the completion of 
surgical closure.  
• 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). 
• 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. 
• 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. 
• Incidence of treatment failure based on pre-defined treatment failure 
criteria (see definition in Section 11.1.3 of the protocol). 
• Incidence of transfusion requirements in the 6 months follow up 
period. 
Sample Size 
The sample size will be of 30 patients completing the study. 15 patients 
will be included in the experimental treatment arm (Group A) and 15 
patients in the active-comparator arm (Group B) to allow an adequate 
comparison between treatments. Dropped patients during the course of 
the study will be replaced. 
Statistical 
Analysis 
Data will be summarized with respect to demographic and baseline 
characteristics, efficacy and safety measurements. The statistical analysis 
will be performed on:  
• Patients’ disposition; 
• Background and baseline characteristics; 
• Concomitant therapies; 
• Safety:  
o adverse events 
o vital signs 
o physical examinations 
o MRI assessment 
o laboratory tests (including testing for antibodies) 
• Efficacy: 
o hemostasis 
o treatment failure 
o re-treatment 
o time to hemostasis 
 

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Data will be summarized separately by treatment arm.  Safety and efficacy 
analyses will be descriptive.  Proportions of patients achieving hemostasis, 
experiencing treatment failure, and needing re-treatment will each be 
estimated along with 95% exact confidence intervals (CIs).  Median time 
to hemostasis from first product application will be estimated using 
Kaplan-Meier methods. 

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2. SCHEDULE OF ASSESSMENTS 
Visit Type 
Screening 
Baseline 
Surgery 
Post-Surgery to 
Hospital Discharge 
(HD) 
Hospital 
Discharge (HD) 
Follow-
Up #1 
Follow-
Up #2 
Follow-
Up #3 
Follow-
Up #4 
Visit N.** 
1 
2* 
3 
4 
5 
6 
7 
8 
9 
Study Day 
D-21 to D-1 
D-1 
D0 
Daily from D1 to D-HD 
D-HD 
D30 (±3) 
D60 (±7) 
D120 
(±14) 
D180 
(±14) 
Informed Consent collection 
x 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria evaluation 
x 
x 
x 
 
 
 
 
 
 
Demographics/Medical History 
x 
 
 
 
 
 
 
 
 
Physical Examination 
x 
x 
 
 
x 
x 
x 
x 
x 
Vital signs1 
x 
x 
x 
x11 
x 
x 
x 
x 
x 
Pregnancy test2 
x 
x 
 
 
 
 
 
 
 
Blood hematology & biochemistry3 
x 
x 
x 
x11 
x 
x 
x 
x 
x 
Urine analysis4 
x 
x 
x 
 
x 
x 
 
 
x 
Coagulation (PT, PTT, INR) 
x 
x 
x 
 
x 
x 
 
 
x 
Serum sample collection5 
x 
 
 
 
 
 
 
 
 
Antibodies testing6 
x 
 
 
 
 
x 
 
 
x 
MRI assessment7 
x 
 
 
 
 
 
 
 
x 
Randomization 
 
 
x 
 
 
 
 
 
 
Product application 
 
 
x 
 
 
 
 
 
 
Operative/Surgical information 
collection8 
 
 
x 
 
 
 
 
 
 
Intra-operative details collection9 
 
 
x 
 
 
 
 
 
 
Determination of hemostasis at TBS10 
 
 
x 
 
 
 
 
 
 
Use of other hemostatic measures 
 
 
x 
 
 
 
 
 
 
Adverse Events 
 
 
x 
x 
x 
x 
x 
x 
x 
Transfusion requirements 
 
 
x 
x 
x 
x 
x 
x 
x 
Bleeding, thrombotic, and  
transfusion-related complications 
 
 
x 
x 
x 
x 
x 
x 
x 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 

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*   
V2 to be skipped in case V1 is performed one day before surgery (D-1).  
**  
All patients can request or be requested to be evaluated in an additional visit (i.e., in case of suspected adverse events).  
1   
Vital signs will include blood pressure, heart rate, temperature, and respiratory rate. 
2  
β-HCG urine pregnancy tests will be conducted in case of patients with childbearing potential. 
3  
Blood hematology and biochemistry tests include: 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. 
4   
Urine analysis tests include: specific gravity, pH, glucose, protein, blood, ketones, microscopic examination. 
5   
A serum sample will be collected and stored at -70°C for possible future viral safety testing. 
6  
Measurement of levels of antibodies against Human Fibrinogen and Human Thrombin. For this purpose, a serum sample will be 
 
collected and stored at -70°C for testing at the end of the study. 
7 
Additional MRI will be performed throughout the study if the investigator identifies signs and symptoms of unanticipated or unexpected 
persistent inflammatory response, or unexplained abdominal pain or other symptoms (for instance signs of adhesions, bowel obstruction, 
etc.). 
8 
Operative/surgical information include OR time, procedure time, time from liver resection/incision to initiation of fascial closure, drain 
usage, estimated blood loss, cell salvage use, transfusion information (if applicable), length of stay (ICU and overall LOS). 
9  
Intra-operative details include hepatic parenchyma classification type (normal or abnormal, steatotic, cirrhotic or other), Investigator 
 
description of the TBS (area, density, arterial/venous/mixed, intensity of flow), alternative methods used to achieve hemostasis (if 
 
applicable), estimated TBS treated area and total resected area, number of product units applied at the TBS and at other areas rather than 
 
the TBS, incidence of post-operative bile leaks requiring intervention, hepatic segment information (anatomic resection/non-anatomic 
 
resection). 
10 
Patients will be monitored for absence of bleeding at 2, 3, 5, 7, and 10 minutes after product application and thereafter, before closing the 
 
site. 
11  
Assessments to be taken daily from one day after surgery (D1) until hospital discharge (D-HD). 

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3. TABLE OF CONTENTS 
 
PROTOCOL SIGNATURE PAGE .......................................................................................................... 3 
INVESTIGATOR’S STATEMENT ......................................................................................................... 4 
1. 
STUDY SYNOPSIS ........................................................................................................................... 5 
2. 
SCHEDULE OF ASSESSMENTS ................................................................................................. 11 
3. 
TABLE OF CONTENTS................................................................................................................. 13 
4. 
ABBREVIATIONS .......................................................................................................................... 15 
5. 
INTRODUCTION............................................................................................................................ 17 
 Product Description ........................................................................................................................... 18 
6. 
STUDY OBJECTIVES .................................................................................................................... 19 
7. 
STUDY DESIGN .............................................................................................................................. 20 
 Overview of Study Design ................................................................................................................. 20 
 Number of Patients ............................................................................................................................ 21 
 Study Discontinuation ........................................................................................................................ 21 
 
Patient Discontinuation Criteria .............................................................................................. 21 
 
Stopping Rules ........................................................................................................................ 21 
 
Premature Termination of the Study ....................................................................................... 22 
 Data Safety Monitoring Board (DSMB) ............................................................................................ 22 
8. 
STUDY POPULATION .................................................................................................................. 23 
 Patient Screening Procedures ............................................................................................................. 23 
 Inclusion Criteria ............................................................................................................................... 23 
 Exclusion Criteria .............................................................................................................................. 23 
9. 
RANDOMIZATION ........................................................................................................................ 24 
10. STUDY PRODUCTS INFORMATION ........................................................................................ 25 
 Formulation ........................................................................................................................................ 25 
 Labeling and Packaging ..................................................................................................................... 25 
 Shipping, Handling and Storage Conditions ...................................................................................... 25 
 Preparation ......................................................................................................................................... 26 
 Dose and Route of Administration ..................................................................................................... 26 
 Study Products Accountability ........................................................................................................... 27 
 Concomitant Medications .................................................................................................................. 27 
 Treatment Compliance ....................................................................................................................... 27 
11. STUDY EVALUATIONS ................................................................................................................ 27 
 Study Procedures ............................................................................................................................... 27 
 
Visit 1 (between Day -21 and Day -1 before Surgery) – Screening Visit ............................... 27 
 
Visit 2 (Day -1 before Surgery) – Baseline Visit .................................................................... 28 
 
Visit 3 (Day 0) – Day of Surgery ............................................................................................ 28 
 
Visit 4 [Day 1 to Day of Hospital Discharge (D-HD)] ........................................................... 31 
 
Visit 5 [Day of Hospital Discharge (D-HD)] .......................................................................... 31 
 
Visit 6 (Day 30±3 after surgery) – Follow up Visit #1 ........................................................... 31 
 
Visit 7 (Day 60±7 after surgery) – Follow up Visit #2 ........................................................... 32 
 
Visit 8 (Day 120±14 after surgery) – Follow up Visit #3 ....................................................... 32 
 
Visit 9 (Day 180±14 after surgery) – Follow up Visit #4 ....................................................... 32 
 Procedures for Handling of Biological Samples ................................................................................ 32 
12. EFFICACY AND SAFETY ASSESSMENTS ............................................................................... 33 
 Primary Endpoint ............................................................................................................................... 33 
 Secondary Endpoints ......................................................................................................................... 33 
13. ASSESSMENT OF ADVERSE EVENTS ...................................................................................... 33 
 Adverse Event (AE) ........................................................................................................................... 33 
 Serious Adverse Event (SAE) ............................................................................................................ 35 
 Suspected Unexpected Serious Adverse Drug Reaction (SUSAR): .................................................. 36 
 SAE Reporting ................................................................................................................................... 36 
 Treatment and Follow-up of Adverse Events .................................................................................... 37 
 Pregnancy Reports ............................................................................................................................. 38 
 Safety reporting to Investigators, IRB(s)/IEC(s) and RA(s)/CA(s) ................................................... 38 
14. STATISTICAL METHODS ........................................................................................................... 38 
14.1 Sample Size Determination ................................................................................................................ 38 

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14.2 Study Population ................................................................................................................................ 38 
14.3 Interim Analysis ................................................................................................................................. 39 
14.4 Handling of Missing Data .................................................................................................................. 39 
14.5 Level of Significance ......................................................................................................................... 39 
14.6 Deviations from the Original Statistical Plan ..................................................................................... 39 
14.7 Data Analysis ..................................................................................................................................... 39 
14.7.1 
Overview of the Patient Disposition ....................................................................................... 39 
14.7.2 
Background and Demographic Characteristics ....................................................................... 39 
14.7.3 
Concomitant Therapies ........................................................................................................... 39 
14.8 Safety & Efficacy Evaluation ............................................................................................................ 39 
14.8.1 
Primary Endpoint .................................................................................................................... 39 
14.8.2 
Secondary Endpoints .............................................................................................................. 40 
14.8.3 
Adverse Events ....................................................................................................................... 40 
14.8.4 
Vital Signs .............................................................................................................................. 41 
14.8.5 
Physical Examination ............................................................................................................. 41 
14.8.6 
Clinical Laboratory Tests ....................................................................................................... 41 
15. STUDY MONITORING.................................................................................................................. 41 
15.1 CRAs and Monitoring Visits.............................................................................................................. 41 
15.2 Primary Source Documents ............................................................................................................... 42 
16. QUALITY ASSURANCE AUDITS................................................................................................ 42 
17. ETHICAL ASPECTS ...................................................................................................................... 43 
17.1 Institutional Review Board (IRB) / Independent Ethics Committee (IEC) ........................................ 43 
17.2 Informed Consent............................................................................................................................... 43 
17.3 Patient Confidentiality ....................................................................................................................... 43 
18. DATA HANDLING AND RECORD KEEPING .......................................................................... 44 
18.1 Data Management Responsibilities .................................................................................................... 44 
18.2 Electronic Data Capture Methods ...................................................................................................... 44 
18.3 Schedule and Content of Reports ....................................................................................................... 44 
18.4 Study Records Retention .................................................................................................................... 44 
18.5 Protocol Deviations ............................................................................................................................ 44 
19. USE OF INFORMATION AND PUBLICATION ........................................................................ 45 
20. REFERENCES ................................................................................................................................. 45 
 

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4. ABBREVIATIONS 
AE  
Adverse Event 
ALT 
Alanine Aminotransferase 
ASA 
American Society of Anesthesiologists 
AST 
Aspartate Aminotransferase 
AT  
Anti-Thrombin 
ATC 
Anatomical Therapeutic Chemical 
BIL 
Bilirubin 
BUN 
Blood Urea Nitrogen 
CA  
Competent Authority 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
DSMB 
Data Safety Monitoring Board 
e-CRF 
Electronic Case Report Form 
ESR 
Erythrocyte Sedimentation Rate 
EU  
European Union 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
Hb  
Hemoglobin 
HC  
Hematocrit 
HD 
Hospital Discharge 
ICH 
International Conference on Harmonization 
ICU 
Intensive Care Unit 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IP  
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intention-to-treat 
IU  
International Unit 
LDH 
Lactate Dehydrogenase 
LLT 
Lowest Level Term 
LOS 
Length of Stay 
MCH 
Mean Cell Hemoglobin 
MCHC 
Mean Cell Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA  Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
OR  
Operating Room 
PCL 
Poly-Caprolactone 
PEG 
Polyethylene Glycol 
PhV 
Pharmacovigilance 

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PLA 
Poly-Lactide Acid 
PLT 
Platelets 
QPPV 
Qualified Person Responsible for Pharmacovigilance  
RA  
Regulatory Authority 
RBC 
Red Blood Cells 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SGOT  
Serum Glutamic Oxaloacetic Transaminase 
SGPT  
Serum Glutamic Pyruvic Transaminase 
SOP 
Standard Operating Procedures 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TAH 
Topical Absorbable Hemostats 
TBS 
Target Bleeding Site 
TMF 
Trial Master File 
TTHP 
Time to Hemostasis from First Product Application 
TTHR 
Time to Hemostasis from Patient Randomization 
US  
United States 
U.S.A. 
United States of America 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 
 
 

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5. INTRODUCTION 
The success of any surgical procedure is based on adequate hemostasis (ref. 1). Ineffective local 
hemostasis is the major cause of bleeding during surgery, but many other causes may be involved.  
During surgery or in the surgical management of trauma, Investigators encounter bleeding from a 
variety of tissue types.  The selection of appropriate methods or products for the control of bleeding 
is dependent upon many factors, which include but are not limited to bleeding severity, anatomical 
location of the source and the proximity of adjacent critical structures, whether the bleeding is 
from a discrete source or from a broader surface area, visibility and precise identification of the 
source and access to the source. Tissue type and fragility/friability, coagulation system status and 
patient stability are also factors for consideration. 
Major bleeding can be controlled by standard surgical techniques, such as stitches, ligatures, or 
clips. Chemical, thermal, and mechanical procedures can be used during surgery to achieve 
hemostasis, especially when diffuse hemorrhages occur. Surgical tools such as electrocautery, 
argon beamer, or laser are often useful. However, sometimes these methods do not achieve 
satisfying results, generating medical consequences and related costs (ref. 2).  
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 
(ref. 3). These products include topical absorbable hemostats (TAH) such as oxidized regenerated 
cellulose, gelatin in various forms with or without a topical thrombin solution, and collagen 
powder, as well as biologically active topical hemostatic products (topical thrombin solutions, 
fibrin sealants, fibrin patches, etc.) and a variety of synthetic topical sealants (ref. 4-7). 
The products that can be used during surgery may be classified as topical hemostats, sealants, and 
adhesives (ref. 3). Hemostats can clot blood. Sealants can create sealing barriers. Adhesives bond 
tissue together. Collagen, gelatin, and cellulose are hemostatic agents. 
The term <fibrin sealant= denotes a product containing coagulation factors, to be administered 
topically to produce a fibrin clot. Typical fibrin sealant products contain human fibrinogen, as a 
substrate of the clot and biologically active thrombin, which converts the fibrinogen to fibrin.  
The intended benefit of the topical fibrin sealant application is to support local hemostasis, or 
<gluing= together of surfaces of injured tissues in order to obtain adaption or sealing of surfaces, 
to support sutures, or to improve repair and healing. Fibrin sealants have been used to support local 
hemostasis in surgical situations where tight tissue sealing is required, and the usage of other 
conventional surgical hemostatic means is not possible. Usage of this type of products is therefore 
particularly justified in surgical procedures involving parenchymal organs such as liver and lung, 
and/or where rapid reliable hemostasis is required.  
Most TAH and fibrin sealant 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. Fibrin 
sealants lack the mechanical strength needed to withstand the force of active hemorrhage and are 
not indicated for use in such settings. Investigators regularly encounter active and/or brisk bleeding 
for which traditional methods of control are ineffective or are impractical and for which currently 
available adjunctive products perform unsatisfactorily. In these instances, Investigators need to 
use a variety of methods and products, frequently sequentially, to control the bleeding. This can 
include prolonged surgical packing. 
 

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Fibrin patches are thought to be useful as hemostats in cases of active and/or brisk bleeding. The 
current approved fibrin patches include EVARREST® and TACHOSIL®. Both products are 
expensive. There is still a need for more cost- effective products or techniques to rapidly control 
active and/or brisk bleeding when treatment with conventional surgical techniques or conventional 
adjunctive hemostatic products is either ineffective or impractical. 
Sealantium Medical Ltd. has developed a new product, sFilm-FS, aimed to help controlling of 
body fluid leakage in general surgery procedures, therefore proposing its use as an adjunct to 
hemostasis and/or sealing. sFilm-FS has been developed to help Investigators controlling 
hemorrhage and does not require a dry surgical surface for effective application. sFilm-FS is a 
cost-effective product as the quantities of fibrin sealant embedded into the product are minimal. 
sFilm is a transparent flexible product, therefore increasing its ease of use and allowing 
Investigators to see the target bleeding site through the application.  
sFilm-FS is currently intended to be used as an adjunct to hemostasis in liver bleeding during 
elective surgery, when control of bleeding by standard surgical methods of hemostasis (such as 
suture, ligature, cautery) is ineffective or impractical.    
 Product Description 
sFilm-FS is a sterile bio-compatible bio-absorbable patch which consists of a polymeric film 
composed of a tri-block polymer (device component) containing Polyethylene Glycol (PEG) Poly-
Caprolactone (PCL) and Poly-Lactide Acid (PLA), embedded with lyophilized powders of Human 
Fibrinogen, Human Thrombin (biological components) and calcium chloride. The composition of 
sFilm-FS is presented in Table 1. 
 
Table 1: sFilm-FS Composition 
Component 
Amount/Patch* 
Function 
Co-Polymer Film: 
 
 
Polyethylene Glycol (PEG) 
(mg) 
66 ± 3.6 
Backbone hydrophilic 
component 
Poly-Caprolactone (PCL) 
(mg) 
153.3 ± 8.4 
Backbone hydrophobic 
component 
Poly-Lactide acid (PLA) (mg) 
5.7 ± 0.3 
Backbone hydrophobic 
component 
Indigo Blue (µg) 
4.5 ± 2 
Dye component 
Coating: 
 
 
Human Fibrinogen (mg) 
21.0 ± 0.5 
Clotting component (substrate) 
Human Thrombin (IU) 
24.0 ± 0.5 
Clotting component (enzyme) 
CaCl2 (mg) 
1.2 ± 0.3 
Cofactor 
1 Based on the weights of the components in the final patch; patch size 5 x 5 cm2 

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The polymeric film consists of a di-block polymer containing PEG and PLA, with the permutations 
to the polymer microstructure by addition of PCL to the synthesis mixture, which extends the 
degradation rate of the co-polymer. All the co-polymer components (PEG, PCL, and PLA) are 
used in approved implantable devices (CoSeal®, Monocryl®, Artelon®, Ligafix®, PREVADH®). 
The lyophilized biological components (Human Fibrinogen and Human Thrombin) are licensed 
components (CSL Behring GmBH). The Human Fibrinogen is identical to the RiaSTAP product 
(STN # 125317/0, CSL Behring) used for treatment of acute bleeding in patients with congenital 
fibrinogen deficiency, afibrinogenemia and hypofibrinogenemia.  The Human Thrombin 
component is approved for further manufacturing use (BLA FFMU STN #125357/0) and is being 
used in the manufacture of fibrin sealants. Human Fibrinogen and Human Thrombin components 
are equivalent to endogenous proteins, with well understood functional effect (ref. 8-10). These 
components are included in sFilm-FS in a relatively low amounts, compared to the amount of the 
same components used in EVARREST® or TACHOSIL® fibrin patches (see Table 2 below).  
 
Table 2: Fibrin Sealants Components*  
Product 
Fibrinogen 
Amount* 
(mg/cm2) 
Thrombin 
Amount*  
(IU/cm2) 
App. Fib:Thr 
Ratio  
(mg : IU) 
EVARREST® 
8.6 
37 
1:4 
TACHOSIL® 
5.5 
2.0 
2:1 
sFilm-FS 
0.84 
0.96 
1:1 
* Refers to nominal amounts 
** In EU SmPC the nominal numbers are 8.1 mg/cm2 for Fibrinogen and 40 IU/cm2 for Thrombin 
 
The polymeric film is durable, flexible, transparent, and non-permeable to body fluids. sFilm-FS 
is biodegradable. Within sFilm-FS manufacturing process, the lyophilized biological components 
are embedded onto the polymeric film using a unique printing method.  
Preclinical safety and toxicological evaluations of sFilm-FS and its constituent components have 
uncovered no concern for risks of particular severity or seriousness and support the use of the 
product in the proposed clinical trial. See Investigator’s Brochure for further details. 
 
6. STUDY OBJECTIVES 
The primary objective of this study is to evaluate the safety of sFilm-FS versus an                      
active-comparator (TACHOSIL®) when used as adjunct to conventional hemostatic techniques 
during elective surgery in which liver bleeding is encountered.  
The secondary objective of this study is to preliminarily evaluate the hemostatic efficacy of sFilm-
FS in in controlling liver bleeding during elective surgery. 
 
 

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7. STUDY DESIGN 
 
 Overview of Study Design 
This is a Phase I/II randomized, prospective, controlled, multi-center, open-label, two-arms study 
evaluating the safety and preliminary efficacy of sFilm-FS in in controlling liver bleeding during 
elective surgery, when conventional methods of control are ineffective or impractical. Patients will 
be randomized with a 1:1 allocation ratio to either sFilm-FS (investigational product) or 
TACHOSIL® (active-comparator).  
The surgical procedure will be performed as per standard of care at the investigational site. A target 
bleeding site (TBS) will be identified intra-operatively by the Investigator following transection 
of the hepatic parenchyma. 
Target Bleeding Site (TBS) is defined as the first bleeding site in which conventional methods of 
bleeding control (i.e., suture, ligature, cautery) are ineffective or impractical. The TBS must be a 
site where occlusion of the injured surface blood vessels is required to achieve hemostasis. It must 
be possible to cover the TBS adequately, with an appropriate overlap, using a single unit of product 
(sFilm-FS or TACHOSIL®). This excludes bleeding from large defects in large arteries or veins 
requiring repair. 
The TBS is the only site or region to be evaluated for hemostasis in this clinical study. If additional 
bleeding sites/regions requiring a topical hemostatic product are identified after the treatment of 
the initial target bleeding site, these bleeding sites should be treated with the same study 
medication according to the patient’s randomization assignment, if clinically appropriate. These 
areas will not be assessed for hemostasis, but information will be collected. 
Once the TBS has been identified (intra-operatively), the Investigator will immediately enroll and 
randomize the Patient into one of the following treatment arms:  
• Group A (investigational product): sFilm-FS will be applied at the target bleeding site 
immediately after conventional methods of control have been exhausted. The sFilm-FS 
should adequately cover the entire target bleeding site. After application of sFilm-FS, the 
Investigator will immediately apply manual compression continuously for at least 2 
minutes. A surgical sponge may be used to assist in providing adequate pressure. 
Hemostasis will be assessed after carefully releasing the compression at the site. sFilm-FS 
should not be removed once bleeding has stopped. A maximum of 4 units of sFilm-FS may 
be used per patient. 
• Group B (active comparator): TACHOSIL® will be applied at the target bleeding site 
immediately after conventional methods of control have been exhausted. TACHOSIL® 
should be applied as per the approved prescribing information, with a manual compression 
of at least 3 minutes. A maximum of 4 units of TACHOSIL® may be used per patient. 
Patients will be then monitored for a total period of 6 months following surgery. Patients will be 
evaluated at study site at Screening Visit (Visit 1, between Day -21 and Day -1), Visit 2 (1 day 
before surgery), Visit 3 (Day 0, the day of surgery), Visit 4 (daily assessments post-surgery until 
the day before hospital discharge), Visit 5 (assessments post-surgery, the day of hospital 
discharge), Visit 6 (control visit 1; at 30 ± 3 days post-surgery) and Visit 7 (control visit 2; at 180 
± 14 days post-surgery). Monitoring of patients will include a list of evaluations, including vital 
signs, physical examination, blood, and urine sampling, MRI assessment, evaluation of antibodies 
for Human Fibrinogen and Human Thrombin, recording of adverse events, transfusion 
requirements and concomitant medications, as indicated in the Schedule of Assessments. Efficacy 
assessment will be evaluated intra-operatively by evaluation of hemostasis before patient’s 
surgical closure.  

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The study will be monitored by an independent Data Safety Monitoring Board (DSMB). The 
DSMB will have responsibility for the review of data and identification of any potential safety 
issues throughout the study. If necessary, the DSMB will make recommendations regarding 
protocol revisions, and will recommend whether the study should proceed based on the safety data 
considering established stopping rules.   
 Number of Patients 
The sample size will be of 30 patients completing the study. 15 patients will be included in the 
experimental treatment arm (Group A) and 15 patients in the active-comparator arm (Group B) to 
allow an adequate comparison between treatments. Dropped patients during the course of the study 
will be replaced. 
 Study Discontinuation 
 Patient Discontinuation Criteria 
All randomized patients should be encouraged to remain in the study until they have completed 
the follow-up visits.  Patients may discontinue participation in the study at any time and for any 
reason.  However, if the patient decides to discontinue participation in the study, the reason must 
be documented when possible.  Reasons for early withdrawal include, but are not limited to: 
• Consent withdrawn by the patient; 
• Patient refusal to complete study visits and/or procedures; 
• Lost-to-follow-up: a certified letter will be sent to the patient at their last known address, 
after a minimum of three attempts to reach the patient by telephone have failed.  If 
communication via certified letter is unsuccessful, the patient will be considered lost-to-
follow-up.  
Patients who discontinue from the study prematurely will be replaced. 
Note: The eCRF should be completed as far as possible and all data relating to the patient prior 
to discontinuation will be made available to the Sponsor or its designee and DSMB. 
 Stopping Rules 
If one of the following occurs during the enrollment period of patients receiving the test article 
(sFilm-FS) the study will be immediately suspended: 
• Three or more patients developed a suspected unexpected serious adverse reaction 
(SUSAR) caused by a TBS post-operative re-bleeding (not requiring surgery                      
re-intervention); 
• Two or more patients had a TBS re-bleeding events following final observation period that 
required surgery re-intervention; 
• Three or more patients developed other possible serious adverse reactions like 
thromboembolic events or severe allergic reactions. 
• Three or more patients develop serious unanticipated or unexpected local reactions (serious 
adverse events) such as:  
o Signs of local reactions affecting the spleen and liver (persistent pain in the area of 
the application that is unanticipated or unexpected) 
o Persistent unanticipated and unexpected Systemic inflammatory response 
syndrome (SIRS), defined with at least two of these conditions: body temperature 
over 38 or under 36 degrees Celsius, heart rate greater than 90 beats/minute or 
respiratory rate greater than 20 breaths/minute or partial pressure of CO2 less than 

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32 mmHg, leucocyte count greater than 12000 or less than 4000 /microliters or over 
10% immature forms or bands  
o Reactions on other local organs such as adhesions and reactions impacting the 
intestinal tract etc., assessed as being due to local reactivity.  This would be 
diagnosed as a bowel obstruction that is unanticipated.   
These stopping rules only apply to the investigational treatment group (Group A). The active-
comparator group (Group B) patients should be followed according to the Investigator’s standard 
practice as clinically appropriate. 
After study suspension, the Data Safety Monitoring Board (DSMB), together with the Sponsor, 
will review the data and decide whether to continue or terminate the study. 
 Premature Termination of the Study 
The Sponsor reserves the right to discontinue the study at any time. Premature termination of the 
study can be conducted voluntary by the Sponsor or by a regulatory agency at any time during the 
course of the study. Premature termination of the study can also be requested by the independent 
DSMB.  
If the study is terminated for any reason, every attempt will be made to complete a follow-up visit, 
in which the patient will have a further blood sample taken for hematology and coagulation tests 
and a physical examination. In case of an adverse event, the patient will be followed-up until the 
event has been resolved or has been stabilized and no further change is expected.  
 Data Safety Monitoring Board (DSMB) 
A DSMB will be convened for this study and will review the results of the trial at regular intervals, 
including safety reports, to protect patients participating in the study. 
DSMB will make recommendations to the Sponsor regarding protocol revisions and will 
recommend whether the study should be closed prematurely based on safety concerns.  For this, 
DSMB will receive timely all reports of patients with adverse events and patients discontinued 
from the study, with particular attention to patients who had intra-operative TBS re-bleeding 
events following final observation period that required re-intervention, patients with serious 
adverse event related to TBS post-operative re-bleeding, and patients who developed a suspected 
unexpected serious adverse reaction (SUSAR) following product application.  
DSMB will operate based on a DSMB Charters. The charter will define the primary 
responsibilities of the DSMB, its relationship with other trial components, its membership, and the 
purpose and timing of its meetings. The charter will also provide the procedures for ensuring 
confidentiality and proper communication.  
The DSMB will consist of at least three members, appointed by the Sponsor, who have agreed to 
serve. The DSMB includes experts in or representatives of the fields of relevant clinical expertise 
and clinical trial methodology. 
At the first meeting of the DSMB, the individual members will vote to determine who will serve 
as the Chairperson. The Chairperson is responsible for overseeing the meetings and developing 
the agenda of DSMB meetings. The chairperson is the contact person for the DSMB. Periodic 
reports from the DSMB will be provided to the Sponsor. The Sponsor (or its designee), in turn, 
will submit these reports to the EC/IRB of each study investigational site in a timely manner. 
HEM-01-17 Study is in compliance with the Guideline on Data Monitoring Committee, 
EMEA/CHMP/EWP/5872/03 Corr. of 27-7-2005. 
 

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8. STUDY POPULATION 
 
 Patient Screening Procedures 
All patients requiring surgery in which liver bleeding will be encountered will be screened by each 
center for study inclusion. For each patient screened, all data will be registered in the eCRF, 
including the reason/s for exclusion for patients who are ineligible for enrollment.  
Final enrollment of patients with be based on meeting all criteria, including intra-operative criteria 
observed at day of surgery (Day 0). 
 Inclusion Criteria 
1. Patients aged ≥ 18 years old. 
2. Patients requiring elective surgery in which liver bleeding will be encountered. 
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 surgery in which 
liver bleeding will be encountered. TBS definition is provided in Section 7.1. 
 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 (ref. 11). 
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 Child-Pugh 
with 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 

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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 with a TBS identified 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. 
 
* Adequate contraceptive methods may include any approved method of birth control such as 
combined estrogen and progestogen containing hormonal contraception, associated with 
inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal 
contraception associated with inhibition of ovulation (oral, injectable, implantable), intra-uterine 
devices, condoms, abstinence or vasectomized partner. Contraception should be maintained until 
study end. 
 
9. RANDOMIZATION 
This is a randomized, open label, two-arm clinical trial. Patients enrolled will be randomized in a 
1:1 ratio to receive the investigational product sFilm-FS or the active-comparator TACHOSIL®. 
Each site will be provided by the CRO/Sponsor with a set of computer-generated randomization 
paper envelopes, each of them bearing the patient randomization number, and containing the 
treatment allocation.  
The investigational sites will be provided with a dedicated <Instructions for Randomization= 
document to ensure consistency in the process. 
Given the differences in appearance between treatment and control products, it will not be possible 
for the Investigator to be blinded to the treatment. However, to avoid any bias in the conduct of 
the surgical procedure, randomization should only take place after completion of the following 
steps: 
• Both study medications (investigational product and active-comparator) will be available 
in the operating room, ready for use; 
• The Investigator will perform the surgical procedure according to his/her standard of care; 
• Once the Investigator encounters an appropriate TBS, related to the primary operative 
procedure, randomization will immediately take place and the randomization envelope will 
be opened. 
 

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10.  STUDY PRODUCTS INFORMATION 
 
 Formulation 
The formulation of both the investigational product (sFilm-FS) and the active-comparator 
(TACHOSIL®) is summarized below: 
• Investigational Product (Group A): sFilm-FS is a topical sterile bio-compatible bio-
absorbable patch which consists of a polymeric film composed of a tri-block polymer 
(device component) containing Polyethylene Glycol (PEG), Poly-Caprolactone (PCL) and 
Poly-Lactide Acid (PLA), embedded with lyophilized powders of Human Fibrinogen, 
Human Thrombin (biological components) and calcium chloride. The lyophilized 
biological components of sFilm are purchased from an approved supplier (CSL Behring) 
and are well established components approved in US and in EU. sFilm-FS is manufactured 
at GMP facility at Nextar Ltd. ISRAEL, under the supervision of Sealantium Medical Ltd. 
– Ha'Amal 11 St. Rosh Ha'Ayin, ISRAEL. sFilm-FS is provided in patches of 5 x 5 cm (~2 
x 2 inch) size.  Upon opening of the sterile package, the product is ready for use. 
• Active-comparator (Group B): TACHOSIL® is a licensed topical fibrin sealant patch 
consisting of Human Fibrinogen and Human Thrombin coated onto an equine collagen 
sponge. The product is manufactured by Takeda Austria GmbH. The product is ready for 
use. For this study, the product will be supplied in patch sizes of 4.8 x 4.8 cm (1.9 x 1.9 
inch). 
 Labeling and Packaging 
The labeling and packaging of both the investigational product (sFilm-FS) and the active 
comparator (TACHOSIL®) is summarized below: 
• Investigational Product (Group A): each unit of sFilm-FS patch is packaged in a polyester 
tray and lid assembly, sealed with a Tyvek paper. The sealed product is included in an outer 
pouch composed of polyester laminated aluminum foil. The tray/lid assembly maintains 
product integrity during storage and transport and serve as barrier to microbial 
contamination. The outer aluminum pouch serves as a barrier to light, moisture, and 
microbial contamination. The outer pouch will be labeled according to the US and EU 
and/or local relevant guidance documents. 
• Active comparator (Group B): each unit of TACHOSIL® patch is packaged in an 
appropriately sized blister pack of polystyrene formed foil and grid varnish coated 
medicinal paper and overwrapped with an aluminum laminated foil pack with a desiccant 
bag. The product is marketed with its own approved label. For the purpose of this clinical 
study an additional label will be added on the product package with specific details as 
required according to the US and EU relevant guidance documents.  
 Shipping, Handling and Storage Conditions  
Both products (investigational and active-comparator) will be supplied free of charge by 
Sealantium Medical Ltd. – Ha'Amal 11 St. Rosh Ha'Ayin, Israel.  Distribution to the clinical 
centers will be performed by a qualified person (QP) or appropriate distribution center with proper 
inventory and quality control capabilities.  
• Investigational Product (Group A): sFilm-FS should be shipped under controlled 
refrigerated conditions (2 to 8 ºC). Unopened packages should be stored in a refrigerator 
at 2 to 8 ºC. Once opened, the product can remain in the sterile field for few hours 
throughout the surgical procedure but must be kept dry to avoid pre-activation. Unused, 

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open product should be appropriately discarded. 
• Active-comparator (Group B): unopened packages of TACHOSIL® should be stored at      
2-25 °C until use. See TACHOSIL® Prescribing Information for further information. 
 
 Preparation  
Both the Investigational product (sFilm-FS) and the active comparator (TACHOSIL®) come ready 
to use in sterile packages and must be handled using sterile technique in aseptic conditions. Use 
only undamaged packages. Once the package is opened, re-sterilization is not possible. Both 
products do not require any preparation.  
The following procedure for opening and applying the product should be followed, to ensure that 
the sterility of the products is maintained: 
• Investigational Product (Group A): sFilm-FS should be brought into the operating room 
and the outer aluminum foil be cleansed before transition into the sterile field. Within the 
sterile field, the Tyvec should then be manually peeled, and the lid should be manually 
removed to discover the patch.  The Tyvec and the lid should then be discarded. The tray 
contains the sFilm-FS with the active side facing downwards. The active side is powdery 
and white to off white in color and opaque.  The non-active side is shiny white to off white 
with imprinted letters <SM1= in two opposite corners. sFilm-FS may be removed from the 
tray using forceps and handled taking care that active side is facing upwards and does not 
come in contact with any wet materials, to avoid any clotting reaction during handling. The 
opened sFilm-FS can remain in the sterile field to be available for use throughout the 
procedure but must be kept dry and should be discarded appropriately at the end of the 
procedure. sFilm-FS must be kept dry at all times before application to avoid pre-
activation.  
• Active comparator (Group B): TACHOSIL® should be brought into the operating room 
and the outer aluminum foil be cleansed before transition into the sterile field.  Within the 
sterile field, both the outer aluminum foil pouch the inner sterile will be opened. 
TACHOSIL® should be prepared and handled in accordance with the approved Prescribing 
Information. 
 Dose and Route of Administration 
Both the investigational product and the control active comparator are for topical (epilesional) use. 
Up to 4 patches may be applied per patient.  

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 Study Products Accountability 
Accountability for the study product at the investigational site is the responsibility of the 
Investigator. The Investigator will ensure that the study products are used only in accordance with 
this study protocol. 
Study product accountability records indicating the product’s delivery date to the site, inventory 
at the site, administered to each patient, and will be maintained by the clinical site. Accountability 
records will contain information on the date of products (both investigational and control products) 
administration, patient ID and quantity of study products dispensed including batch/serial 
numbers, expiration dates, details of any remaining product, and subsequent destruction. The study 
CRA will verify this log during the course of the study.  
It is required that all study products, including empty packages, will be stored at the study 
investigational sites until the Sponsor or its designee has verified the study product accountability 
and made a reconciliation between delivered / used / unused product units at site. The unused 
product units will be returned to Sponsor before the study closure at the investigational sites. 
 Concomitant Medications 
The use of any other topical hemostat, except fibrin sealants or topical thrombin, at the TBS will 
be permitted once the observational period is completed and hemostasis was not achieved or in the 
event of breakthrough bleeding requiring further treatment (as deemed necessary by the 
Investigator).   
For additional bleeding sites, separate from the TBS, patients must be treated with the same study 
article according to the randomization assignment, when clinically appropriate. If other hemostatic 
products are needed the Investigator should revert to his/her standard of care (excluding fibrin 
sealants and topical thrombin).  
Administration of all medications, including indication, dose, frequency, and route of 
administration will be recorded in the source documentation file and in the electronic Case Report 
Form (eCRF). All concomitant medications will be discussed and documented at each visit.  
 Treatment Compliance 
All study products will be administered by study center personnel. Details of administration of 
study medication, including time of application and whether more than one dose was administered, 
will be recorded by the Investigator in the Case Report Form (eCRF).  
 
11.  STUDY EVALUATIONS 
 
 Study Procedures 
The Schedule of Assessment included in the synopsis summarizes the frequency and timing of the 
study procedures. Data collected for the patient during the study will be recorded in the patient’s 
medical records, and study worksheets/source documents, as appropriate, and will be transcribed 
into the eCRF. 
 Visit 1 (between Day -21 and Day -1 before Surgery) – Screening Visit 
Prospective patients will be screened within 21 days prior to surgery. Prior to performing any study 
activities/evaluations, the patient must be thoroughly informed about all aspects of the study, 
including scheduled study visits and activities, and must sign the informed consent form. Signed 

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copies of the informed consent forms should be given to the patient. During this visit the patient 
will be assigned a screening number by the Investigator in sequential order.  
During the visit, the Investigator will collect the following information, which will be recorded in 
the study eCRF and study file (when required): 
• Informed Consent collection. 
• Allocation of screening number. 
• Demography / Medical history. 
• Physical examination. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Pregnancy test (β-HCG urine test) for female patients of childbearing potential. 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 
• Levels of antibodies against Human Fibrinogen and Human Thrombin. For this purpose, a 
serum sample will be collected and stored at -70°C for testing at the end of the study. 
• MRI assessment of the intervention site. Additional MRI will be performed throughout the 
study if the investigator identifies signs and symptoms of unanticipated or unexpected 
persistent inflammatory response, or unexplained abdominal pain or other symptoms (for 
instance signs of adhesions, bowel obstruction, etc.). 
• An additional serum sample will be collected and stored at -70°C for possible future viral 
safety testing. 
• Eligibility Criteria evaluation. In the event that a Patient is not eligible, the reason will be 
documented on the eCRF and screening log. 
• Concomitant Medications. 
 Visit 2 (Day -1 before Surgery) – Baseline Visit 
The following activities will be performed within 24 hours prior to the surgical procedure. Visit 2 
will be skipped in case V1 is performed at Day -1.  
Eligibility Criteria evaluation. In the event that a patient is not eligible, the reason will be 
documented on the eCRF and screening log. 
• Physical examination and documentation of any changes in medical history from the 
screening visit. 
• Eligibility Criteria verification. In the event that a Patient is not eligible, the reason will be 
documented on the eCRF and screening log. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Pregnancy test (β-HCG urine test) for female patients of childbearing potential. 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 
• Concomitant medications documentation during 24 hours prior to surgery. 
 Visit 3 (Day 0) – Day of Surgery 
During this visit the patient will undergo the surgical procedure. The Investigator will use his/her 
standard surgical techniques for the surgical procedure. Patients identified intra-operatively by the 
Investigator to have an appropriate target bleeding site and to be eligible to enter the study, will be 
enrolled and randomized to receive topical application of either sFilm-FS (investigational product) 

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or TACHOSIL® (active-comparator) at the target bleeding site. The TBS will be identified and 
will be the only specific site or region to be evaluated for efficacy in this clinical study. 
The below activities will be performed, and information will be collected during the surgical 
procedure. All activities will be recorded in the eCRF and study file. 
Before Randomization 
The Investigator will perform the surgical intervention according to his/her standard of care.  When 
the Investigator encounters the first appropriate TBS in the surgical area that requires an adjunct 
to achieve hemostasis because traditional methods have been determined to be ineffective or 
impractical, he/she will evaluate the patient for intra-operative eligibility and record all details 
related to the TBS. 
Randomization 
Once intra-operative eligibility is confirmed, and the TBS is defined, the patient will then be 
randomized immediately by opening the appropriate randomization paper envelope. The clock will 
then be started. This time point will be considered TP-00. The time and randomization/patient 
number will be recorded. 
Following Randomization 
Following randomization, the treatment medication assigned (either sFilm-FS or TACHOSIL®) 
will be applied.   
Prior to application the patch can be cut to the correct size and shape if desired. The patch should 
cover the TBS and extend 1 to 2 cm beyond the margins of the wound. Only a single unit of product 
may be applied at a time at the identified TBS. 
Prior to application, the area to be treated should be rinsed to remove disinfectants and other fluids. 
The fibrinogen and thrombin proteins can be denatured by alcohol, iodine or heavy metal ions. If 
any of these substances have been used to clean the wound area, thoroughly irrigate the area before 
the application.  
The time of application will be considered TP-01 and will be recorded as such. If the sFilm-FS is 
to be used, do not moisten the product prior to application, as the product will be activated 
immediately. TACHOSIL® should be used in accordance with the approved Prescribing 
Information. 
Following product application, manual compression will be applied and will be maintained for at 
least 2 minutes for sFilm-FS and for at least 3 minutes for TACHOSIL®, until examination of TBS. 
The Investigator may use a surgical sponge (laparotomy pad or surgical gauze) to assist in 
providing adequate pressure to stem all bleeding over the entire treated surface area at the TBS. 
Hemostasis will then be assessed by carefully releasing manual compression and removing the 
surgical sponge (if used) without disturbing the hemostasis product. The product unit should be 
left in place once it adheres to organ tissue.  
In case hemostasis is not achieved within 2 minutes (for sFilm-FS) or 3 minutes (for 
TACHOSIL®), the surgeon will wait 2 additional minutes applying additional pressure on the 
gauze before carefully releasing manual compression and checking again. 
Hemostasis will be assessed at 2 (for sFilm-FS only), 3, 5, 7 and 10 minutes following product 
application. These time points will be recorded as TP-02, TP03, TP-05, TP-07 and TP-10 
respectively.  
Re-treatment: If the surgeon is not satisfied with the placement of the patch, or if hemostasis is not 
achieved, or if during the subsequent observation period bleeding requiring treatment recurs, the 

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Investigator may decide to apply an additional product unit as specified above. In this case, the 
already applied product unit should not be removed, unless it did not adhere to the TBS.  
The time point of product re-application will be recorded as TPR-01. After re-treatment 
application, manual compression must be applied for at least 2 (for sFilm-FS) or 3 minutes (for 
TACHOSIL®, as described above. Hemostasis will then be assessed following product re-
application at any time-points within the original 10 minutes observation period (TPR-02, TPR-
03 or other) and until site closure. A minimum of 5 minutes observation period at the TBS has to 
take place before site closure. The time followed by 5-minutes observation period to assess 
hemostasis will be recorded.   
Hemostasis is defined as an absence/cessation of bleeding at the TBS according to the surgeon’s 
judgement, so that the surgical closure of the field could be started. Time to hemostasis (TTH) is 
defined as time until hemostasis is achieved. TTHP will be considered as time from first product 
application and TTHR as time from randomization will be collected as well but will not be used 
as endpoint.  
Treatment failure is defined as follows: 
• in case the bleeding at TBS (or re-bleeding) is still observed after 10 minutes following 
first application of 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 product, at any time. 
In case of treatment failure, the Investigator may revert the treatment to standard of care. If 
additional sites requiring a topical hemostasis product are identified after the treatment of the initial 
target bleeding site, these bleeding sites should be treated with the same treatment article according 
to the patient’s randomization assignment, if clinically appropriate. If other hemostatic products 
are needed, the Investigator should revert to his/her standard of care (excluding fibrin sealants or 
topical thrombin). 
The following information will be collected during surgery and recorded on the eCRF and in the 
study file: 
• Determination of hemostasis at TBS. 
• Use of other hemostatic measures. 
• Collection of intra-operative details including hepatic parenchyma classification type 
(normal or abnormal, steatotic, cirrhotic or other), Investigator description of the TBS 
(area, density, arterial/venous/mixed, intensity of flow), alternative methods used to 
achieve hemostasis (if applicable), estimated TBS treated area and total resected area, 
number of product units applied at the TBS and at other areas rather than the TBS, 
incidence of post-operative bile leaks requiring intervention, hepatic segment information 
(anatomic resection/non-anatomic resection). 
• Collection of operative/surgical information, including OR time, procedure time, time from 
liver resection/incision to initiation of fascial closure, drain usage, estimated blood loss, 
cell salvage use, transfusion information (if applicable), length of stay (ICU and overall 
LOS). 
Additional assessments will be taken at the end of surgery and will include the following: 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 

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• Adverse events from surgery start (in particular related to post-operative adhesions, 
systemic inflammation, bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 4 [Day 1 to Day of Hospital Discharge (D-HD)] 
On Day 1 after surgery and until the day of hospital discharge, daily assessment will be conducted 
and will include: 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 5 [Day of Hospital Discharge (D-HD)] 
At the time of discharge the following assessment will be conducted and recorded on the eCRF 
and in the study file: 
• Physical examination and documentation of any changes in medical history. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 6 (Day 30±3 after surgery) – Follow up Visit #1 
The following information will be recorded at the clinical follow-up visit approximately one month 
following surgery: 
• Physical examination and documentation of any changes in medical history. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 
• Testing of antibodies levels (against Human Fibrinogen and Human Thrombin). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 7 (Day 60±7 after surgery) – Follow up Visit #2 
The following information will be recorded at the clinical follow-up visit approximately one month 
following surgery: 
• Physical examination and documentation of any changes in medical history. 

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• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 8 (Day 120±14 after surgery) – Follow up Visit #3 
The following information will be recorded at the clinical follow-up visit approximately one month 
following surgery: 
• Physical examination and documentation of any changes in medical history. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
 Visit 9 (Day 180±14 after surgery) – Follow up Visit #4 
The following information will be recorded at the clinical follow-up visit approximately six 
months following surgery: 
• Physical examination and documentation of any changes in medical history. 
• Vital signs (blood pressure, heart rate, temperature, respiratory rate). 
• Blood hematology and biochemistry (see Schedule of Assessments for the list of tests). 
• Measurement of coagulation parameters (PT, PTT, INR). 
• Urine analysis (see Schedule of Assessment for the list of tests). 
• Testing of antibodies levels (against Human Fibrinogen and Human Thrombin). 
• MRI assessment of the intervention site (mainly to exclude post-operative adhesions). This 
assessment can be done earlier in patients reporting abdominal symptomatology suspect 
for intra-abdominal adhesions or intestinal obstruction (ref. 12). 
• Adverse events (in particular related to post-operative adhesions, systemic inflammation, 
bleeding / thrombotic and transfusion-related complications). 
• Transfusion requirements. 
• Concomitant medications. 
All patients can request or be requested to be evaluated in an additional visit (i.e., in case of 
suspected adverse events). In such case will be examined as needed indicated at Section 13.5.  
 Procedures for Handling of Biological Samples 
All laboratory investigations will be performed at the local hospital laboratory. The volume of 
blood to be taken will be determined according to the standard practices of each hospital. The 
normal reference ranges and laboratory accreditation certificates will be provided by the local site 
laboratory.  Testing of antibodies (against Human Fibrinogen and Human Thrombin) will be 
performed at a central laboratory. In case of positive results for immunogenicity, an antibody 
retesting using a second separately drawn sample as confirmatory measurement will be performed. 
 

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12.  EFFICACY AND SAFETY ASSESSMENTS 
 
 Primary Endpoint 
The primary endpoint of the study is the evaluation of safety. Safety will be assessed from 
randomization of patients until the last follow-up visit and will include evaluation of treatment 
emergent adverse events.  In particular, patients will be followed for AEs related to bleeding at 
TBS, thrombotic events, transfusion-related complications, post-operative adhesions (MRI 
assessment) as well as vital signs, physical examination, urine analysis, blood / coagulation 
parameters profiles, antibodies against fibrinogen and thrombin, and signs of systemic 
inflammation. For assessment of AEs please see Section 13. 
 Secondary Endpoints 
The secondary endpoints of the study are: 
• 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.  
• 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). 
• 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. 
• 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. 
• Incidence of treatment failure based on pre-defined treatment failure criteria (see definition in 
Section 11.1.3 of the protocol). 
• Incidence of transfusion requirements in the 6 months follow-up period. 
 
 
13.  ASSESSMENT OF ADVERSE EVENTS 
Safety will be assessed in all patients participating in the clinical study including monitoring of 
adverse events, as specified below.  
 Adverse Event (AE) 
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical trial 
patient administered a medicinal product and which does not necessarily have a causal relationship 
with the treatment .  In the study, any adverse event occurring after the clinical trial patient has 
signed the study Informed Consent should be recorded on the eCRF and reported as an AE. An 
adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of an investigational 
medicinal product, whether or not considered related to the investigational medicinal product. A 
new condition or the worsening of a pre-existing condition will be considered an AE. Stable 
chronic conditions such as arthritis that is present prior to study entry and do not worsen during 

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the study will not be considered AE. Medical conditions/diseases present before starting study are 
only considered adverse events if they worsen after starting study treatment. 
Abnormal results of diagnostic procedures, including abnormal laboratory findings, will be 
considered an AE if it: 
• it is associated with significant clinical signs or symptoms; 
• requires therapy. 
Post-operative adhesions will be considered adverse events in this study. A MRI assessment will 
be performed at Visit 1 (Screening) and at Visit 7 (6 months post-surgery) for detection of intra-
abdominal adhesions, or earlier in patients reporting abdominal symptomatology suspect for intra-
abdominal adhesions or intestinal obstruction (ref. 12). 
Systemic inflammation will be evaluated by the investigator, based on the following assessments: 
• Body temperature, heart rate, respiratory rate, white blood cell count, CRP 
The intensity or severity of the AE will be characterized as: 
• Mild:              AE which is easily tolerated. 
• Moderate:  
AE sufficiently discomforting to interfere with daily activity. 
• Severe:   
AE which prevents normal daily activities. 
The relationship of an AE to the study product must be assessed by the Investigators using the 
following criteria and definitions: 
Unrelated 
This category applies to those adverse 
events 
which, 
after 
careful 
consideration, are clearly due to 
extraneous 
causes 
(disease, 
environment, etc.) 
 
Unlikely 
In general, this category can be 
considered applicable to those adverse 
events, which after careful medical 
consideration at the time they are 
evaluated, are judged to be unrelated 
to the test drug. 
 
An adverse experience may be considered 
unlikely related if or when (must have two): 
• It is an unknown reaction to the test drug 
• It does not follow a reasonable temporal 
sequence from the administration of the 
test drug. 
• It could have been produced by the 
patient’s clinical state, environmental or 
toxic 
factors, 
or 
other 
treatments 
administered to the patient. 
It does not reappear or worsen when the drug is 
re-administered. 

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Possibly 
This category applies to those adverse 
events for which, after careful medical 
consideration at the time they are 
evaluated, a connection with the test 
drug administration appears unlikely 
but cannot be ruled out with certainty. 
 
An adverse experience may be considered 
possibly related if or when (at least two of the 
following): 
• It follows a reasonable temporal sequence 
from administration of the drug. 
• It could not be produced by the patient’s 
clinical state, environmental or toxic 
factors, or other treatments administered to 
the Patient. 
• It is a known reaction to the test drug. 
Probably 
This category applies to those adverse 
events which, after careful medical 
consideration at the time they are 
evaluated, are felt with a high degree 
of certainty to be related to the test 
drug. 
An adverse experience may be considered 
probably related if or when (at least three of the 
following): 
• It follows a reasonable temporal sequence 
from administration of the drug. 
• It could not be reasonably explained by the 
known characteristics of the patient’s 
clinical state, environmental or toxic 
factors or other modes of therapy 
administered to the patient. 
• It 
disappears 
or 
decreases 
after 
discontinuation (de-challenge) of test drug 
or reduction of posology 
• It is a known reaction to the test drug. 
Definitely 
This category applies to those adverse 
events which, after careful medical 
consideration at the time they are 
evaluated, are considered to be related 
to the test drug. 
An adverse experience may be considered 
certainly related if or when: 
• it follows a reasonable temporal sequence 
from administration to the clinical event - 
including laboratory test abnormalities - 
• which 
cannot 
be 
explained 
by 
a 
concomitant illness or by other medicinal 
products. 
• The reaction must have already been 
observed for the suspected medicinal 
product. 
• The reaction must improve with "de-
challenge" 
and 
reappear 
with 
"re-
challenge". 
 
The date of onset, a description of the AE, severity, seriousness, action taken, relationship to the 
study drug, outcome of the event and date of resolution will be recorded. 
 Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is defined as an AE that results in any of the following: 

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• Death. 
• Life-threatening. 
• Requires hospitalization or prolongs existing in patients’ hospitalization. 
• Results in persistent or significant disability or incapacity. 
• Results in a congenital abnormality or birth defect. 
• An important medical event which requires medical intervention to prevent any of the above 
outcomes. 
<Important medical events= are those which may not be immediately life-threatening but may 
jeopardize the patient and may require intervention to prevent one of the other serious outcomes 
listed above. Examples of such events are intensive treatment in an emergency room or at home 
for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
resulting in an adverse event will normally be considered serious by this criterion. 
<In patient hospitalization or prolongation of existing hospitalization= means that hospital in 
patient admission and/or prolongation of hospital stay were required for treatment of AE, or that 
they occurred as a consequence of the event. It does not refer to pre-planned elective hospital 
admission for treatment of a pre-existing condition that has not significantly worsened, or to 
diagnostic procedure. 
The term "life-threatening" in the definition of "serious" refers to an event in which the patient 
was at risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it was more severe. 
Any new SAE that occurs after the study period and is considered to be related (possibly/probably) 
to the IP or study participation should be recorded and reported immediately. The study period for 
the purpose of SAE reporting is defined as the period from the patient's signature on the informed 
consent form until the end of the follow-up period. 
Events NOT considered to be SAEs are hospitalizations which: 
• Were planned before entry into the study. 
• Are for elective treatment of a condition unrelated to the indication or its treatment. 
• Occur on an emergency, outpatient basis and do not result in admission (unless fulfilling the 
criteria outlined above for a SAE). 
• Are part of the normal treatment or monitoring of the indication and not associated with any 
deterioration in condition. 
 Suspected Unexpected Serious Adverse Drug Reaction (SUSAR): 
An "Unexpected Adverse Drug Reaction" is any noxious and unintended response that is related 
to the administration of an investigational product that has not been reported as expected in the 
Summary of Product’s Characteristics or in the Investigator’s Brochure.  
All SUSARs related to the investigational product will be subject to expedite reporting. 
 SAE Reporting 
Any SAE, whether deemed study medication-related or not, must be reported to the Local Clinical 
Management (CRA and Sponsor Qualified Person Responsible for Pharmacovigilance (QPPV)) 
within 24 hours after the Investigator has become aware of its occurrence, using the SAE form. 
The SAE form completion and reporting must not be delayed even if all of the information is not 

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available at the time of the initial contact. The local Clinical Management will forward the report 
to the Sponsor's QPPV who will handle all the safety reports. 
 
SAE originated in this study should be sent to: 
seQure Life Sciences 
PhV Officer 
safety@sequrelifesciences.com 
Fax: +39-0656561998 
 
Additional information (follow-up) about any SAE unavailable at the initial reporting should be 
forwarded by the site within 24 hours of the information becoming available to the Local Clinical 
Management.  
The following information should be provided on the SAE form to accurately and completely 
record the event: 
• Investigator Name and Investigational site Number. 
• Patient Number. 
• Patient initials. 
• Patient Demographics. 
• Clinical Event: 
✓ Description. 
✓ Date of onset and end date. 
✓ Severity. 
✓ Treatment. 
✓ Relationship to study drug (causality). 
✓ Action taken regarding study drug (none / dose delayed / dose reduced / product 
withdrawn). 
✓ Outcome (completely recovery; sequelae; improvement; persistent; death; 
unknown). 
• If the AE results in Death: 
✓ Cause of death (whether or not the death was related to study drug). 
✓ Autopsy findings (if available). 
• Medical History case report form (copy). 
• Concomitant Medication case report form (copy). 
• Any relevant reports (laboratory, discharge, X-ray, etc). 
SAE must be collected and reported regardless of the time elapsed from the last study. For both 
initial and follow-up SAE reports the Local Management forwards this information to PhV 
responsible within 48 hours. 
 Treatment and Follow-up of Adverse Events 
Adverse events, especially those related to the study drug should be followed up until they have 
resolved (returned to baseline status) or stabilized. All AEs should be followed-up even after the 
Patient's participation in the study is completed, or in case of withdrawal of the Patient from the 

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clinical trial or of anticipated conclusion of the study. In particular, all SAE assessed by the 
Investigator as related to the study drug will continue to be followed-up until 30 days following 
last visit of the study or until SAE is resolved or stabilized. 
If after follow-up, return to baseline status or stabilization cannot be established an explanation 
should be recorded on the eCRF. Any newly emergent SAE after treatment is discontinued or the 
Patient has completed the study and is considered to be related to the IP or study participation 
should be recorded and reported immediately.  
 Pregnancy Reports 
A female Patient participating to the clinical study must be instructed to inform the Investigator 
immediately if she becomes pregnant during the study. Pregnancies occurring up to 90 days after 
the completion of the study drug must also be reported to the Investigator. The Investigator should 
report all pregnancies in female clinical trial Patients to PhV responsible (details above) within 
one working day of becoming aware of them using a clinical trial pregnancy reporting form. All 
pregnancy reports will be captured in the safety database. This includes normal pregnancies 
without an AE. Any Patient who becomes pregnant during the study period must not receive 
additional doses of investigational product and will be withdrawn from the study. If the Patient 
requests to know which treatment she received, this information will be provided to her. The 
pregnancy should be followed for outcome of the mother and the child, including any premature 
terminations, and should be reported to PhV responsible (details above) for any outcome.  
 Safety reporting to Investigators, IRB(s)/IEC(s) and RA(s)/CA(s) 
The Sponsor, via QPPV, or its designee is responsible for reporting all applicable SUSAR via 
EVCTM, to EC that has issued the single opinion. The Sponsor, via QPPV, or its designee is 
responsible for reporting to all Investigators and to other ECs, as applicable, in accordance with 
national regulations in the countries where the study is conducted. The SUSARs will be submitted 
within 7 days for fatal and life-threatening events and within 15 days for other serious events.  
14.  STATISTICAL METHODS 
Data will be summarized with respect to demographic and baseline characteristics, efficacy and 
safety measurements. It is planned that data from all investigational sites participating in the trial 
will be combined. Each analysis will show the results by treatment group and for entire sample. 
14.1 Sample Size Determination 
The sample size will be of 30 patients completing the study. 15 patients will be included in the 
experimental treatment arm (Group A) and 15 patients in the active-comparator arm (Group B) to 
allow an adequate comparison between treatments.  
Dropped patients during the course of the study will be replaced. 
The sample size of 15 patients per arm is sufficient for planned descriptive analyses and 95% 
confidence intervals of efficacy. 
14.2 Study Population 
The Intention-To-Treat (ITT) population will include all Patients registered, who underwent 
surgery and received the dose of study treatment and, with no major violations of the eligibility 
criteria. This population is considered as primary and will be used for all efficacy analyses. 
The safety population will include all patients registered, who received one dose of study 
treatment. This population will be used for safety analysis. 

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14.3 Interim Analysis 
No interim analysis is planned for this trial. 
14.4 Handling of Missing Data 
All efforts will be made to complete and report the observations in the study period and no 
particular approach for missing data after surgery visits will be applied. The primary reason for 
withdrawal from the study should be documented on the appropriate eCRF.  
14.5 Level of Significance 
Hypothesis testing is not specified for this study, rather estimation of efficacy endpoints will be 
accompanied by 95% exact confidence intervals.  
14.6 Deviations from the Original Statistical Plan 
Before database locking, when all data will be included and cleaned into the database, a complete 
and exhaustive Statistical Analysis Plan (SAP) will be redacted.  
The SAP will contain a summary of the study protocol, the changes from original statistical plan, 
a detailed definition of the populations recruited, the description of protocol violators/deviators, 
the patient accountability and the detailed profile of the populations recruited, any other analysis 
concerning the endpoints of the study and the detailed description of safety. 
14.7 Data Analysis 
14.7.1 Overview of the Patient Disposition 
Frequency by center, sample disposition, frequency and listing of major and minor protocol 
violators/deviations and composition of populations (ITT, safety) will be tabulated by treatment 
groups. 
14.7.2 Background and Demographic Characteristics 
Background and demographic characteristics such as age, gender, race, medical history will be 
summarized by treatment groups using appropriate descriptive statistics (mean, standard deviation, 
median and range for continuous variables, and frequencies and percentages for categorical 
variables). If treatment groups are not comparable in any of these variables, additional analyses 
may be performed to adjust for the influence of the variable on the efficacy outcome, if any. 
14.7.3 Concomitant Therapies 
Descriptive statistics such as frequency counts and percentages of Patients who use concomitant 
therapies will be provided by ATC therapy category, preferred term and also by treatment group. 
14.8 Safety & Efficacy Evaluation 
A descriptive analysis of safety and efficacy variables will be performed. 
14.8.1 Primary Endpoint 
The primary endpoint of the study is the evaluation of safety. Safety will be assessed from 
randomization of patients until the last follow-up visit and will include evaluation of treatment 
emergent adverse events.  In particular, patients will be followed for AEs related to bleeding at 
TBS, thrombotic events, transfusion-related complications, post-operative adhesions (MRI 
assessment) as well as vital signs, physical examination, urine analysis, blood / coagulation 

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parameters profiles, antibodies against fibrinogen and thrombin, and signs of systemic 
inflammation. For assessment of AEs please see Section 13. 
Descriptive safety analyses will be summarized separately by treatment arm. 
14.8.2 Secondary Endpoints 
The secondary endpoints of the study are: 
• 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 staring from 10 minutes after product application and until the 
completion of surgical closure.  
• 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). 
• 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. 
• 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. 
• Incidence of treatment failure, based on pre-defined treatment failure criteria (see 
definition in Section 11.1.3 of the protocol). 
• Incidence of transfusion requirements in the 6 months follow up period. 
Descriptive efficacy analyses will be summarized separately by treatment arm.  
Primary analyses will calculate the proportion of patients achieving hemostasis at 3 minutes among 
the sFilm-SF treatment arm.  With 15 patients randomized to sFilm-SF, reasonable confidence 
intervals (CI) can be estimated.  For example, if 80% of the patients achieve hemostasis at 3 
minutes (similar to a TACHOSIL® reported values of 81% for this endpoint), the accompanying 
95% confidence interval (CI) is 52% to 96% (using exact confidence limits).  This CI provides 
evidence that greater than 52% of patients with similar conditions will achieve hemostasis at 3 
minutes.  This will also be reported for the 15 patients randomized to the  TACHOSIL® arm. There 
will be no formal comparison between the two-arms. 
Similarly, proportions of patients and corresponding 95% CIs will be estimated for all of the 
following, separately by treatment arm: 
• achieving hemostasis at TBS at each remaining time point,  
• incidence of re-treatment (separately by time),  
• incidence of treatment failure (as defined in Section 11.1.3), and  
• incidence of transfusion requirements.   
Median time to hemostasis from first product application will be estimated using Kaplan-Meier 
methods; minimum and maximum time will also be reported. 
14.8.3 Adverse Events 
The AEs will be described by System Organ Class, Preferred Term and Lowest Level Term (LLT) 
according to the MedDRA dictionary (Version 19.0). 
The following Adverse events will be tabulated by Patient and preferred term, for each treatment 
group: 

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• any AE; 
• any SAE; 
• any related AE; 
• any AE leading to discontinuation from study. 
This listing, at minimum, will contain a description of AEs as to seriousness, severity, onset date 
and end date, duration, action taken (if any), outcome and relationship. 
Deaths reportable as SAEs and non-fatal serious adverse events will be listed by Patient and 
tabulated by type of adverse event. Any other information collected will be listed as appropriate. 
14.8.4 Vital Signs 
Vital signs will be individually listed. Quantitative parameters will be summarised by using 
descriptive statistics, including the number of values within, lower and upper reference ranges 
(when appropriate). 
14.8.5 Physical Examination 
Patients with any change in physical examination from baseline to time points after dosing will be 
listed. 
14.8.6 Clinical Laboratory Tests 
All laboratory values recorded during the study will be individually listed. Quantitative parameters 
will be summarized by descriptive statistics, including the number of values within, lower and 
upper reference ranges (when appropriate) for blood and coagulation tests. 
 
15. STUDY MONITORING 
 
15.1  CRAs and Monitoring Visits 
The CRA will be responsible for ensuring adherence to EU Directives, ICH guidelines and the 
Sponsor’s or its designee Standard Operating Procedures. The Sponsor or its designee will provide 
study Monitors for this trial. The CRAs will operate according to the EU Directives and in 
compliance with ICH guidelines. Regular monitoring of study data at each site will be performed 
as defined by the study specific monitoring plan. Individual sites will be monitored to verify that 
enrollment rate, data recording, and protocol adherence are satisfactory.  
The frequency of monitoring individual sites may fluctuate depending upon enrollment rate, 
quantity of data collected and the complexity of the study and will be described in the monitoring 
plan. These monitoring visits will be performed for the purposes of verifying adherence to the 
protocol and the completeness. The study CRA will verify eCRF entries by comparing them with 
the primary source documents (hospital/clinic/office records), which will be made available for 
this purpose, and accuracy of data entered on the eCRF. The CRA will review the maintenance of 
regulatory documentation and study product accountability. The monitor will review the progress 
of the study with the Investigator and other site personnel on a regular basis. eCRF sections may 
be collected during these visits. At the end of the study, a close-out monitoring visit will be 
performed. Monitoring visits will be arranged in advance with site personnel at a mutually 
acceptable time. Sufficient time must be allowed by the site personnel for the CRA to review eCRF 
and relevant source documents. The Investigator should be available to answer questions or resolve 
data clarifications. Adequate time and space for these visits will be made available by the 
Investigator. 

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15.2 Primary Source Documents 
The Investigator must maintain primary source documents to support eCRF data entries. These 
documents, which are considered <source data=, may include but are not limited to : 
• Demographic information. 
• Evidence supporting the diagnosis/condition for which the Patient is being studied. 
• General information supporting the Patient’s participation in the study. 
• Medical history and physical findings. 
• Hospitalization or Emergency Room records (if applicable). 
• Each study visits by date, including any relevant findings/notes by the Investigator(s), 
occurrence (or lack) of adverse events, and changes in medication usage, including the date 
the study treatment was commenced and stopped . 
• Any additional visits during the study. 
• Any relevant telephone conversations with the Patient regarding the study or possible 
adverse events. 
• Original, signed informed consent forms for study participation. 
The Investigator must also retain all Patient specific printouts/reports of tests/procedures 
performed as a requirement of the study. During monitoring visits, the monitor will need to verify 
data in the eCRF against these source data. 
 
16.  QUALITY ASSURANCE AUDITS 
The Sponsor or its designee will continuously assess the performance and deliverables as well as 
resource levels to ensure adequate cover. The Sponsor or its representative will maintain and 
guarantee the quality control of the Trial Master File (TMF) containing all essential documents 
relating to the clinical study which allow verification of the conduct of the study and the quality 
of the data generated. 
The Sponsor or its designee may carry out an audit at any time.  
Investigators will be given adequate notice before the audit occurs. The purpose of an audit is to 
confirm that the study is conducted as per study protocol, GCP, and applicable regulatory 
requirements, that the rights and well-being of the Patients enrolled have been protected, and that 
the data relevant for the evaluation of the investigational product have been captured, processed, 
and reported in compliance with the planned arrangements. The Investigator will permit direct 
access to all study documents, device accountability records, medical records, and source data.  
Any steps taken at the investigational site or centrally to ensure the use of standard terminology 
and the collection of accurate, consistent, complete and reliable data, such as training sessions, 
monitoring of Investigators by Sponsor personnel, instruction manuals, data verification, cross-
checking, or data audits should be described. It should be noted whether Investigator meetings or 
other steps will be taken to prepare Investigators and standardize performance.  
Regulatory authorities may perform an inspection of the study, even up to several years after its 
completion. If an inspection is announced, the Sponsor or its designee must be informed 
immediately. 
 

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17.  ETHICAL ASPECTS 
The study will be conducted in accordance with the Declaration of Helsinki (1964), amended Japan 
(1975), Italy (1983), Hong Kong (1989), Republic of South Africa (1996), Scotland (2000), Brazil, 
(2013) and ICH Harmonized Tripartite Guidelines for Good Clinical Practice (1996). 
The Investigator agrees, when signing the protocol, to adhere to the instructions and procedures 
described in it and thereby to adhere to the principles of Good Clinical Practice that it conforms 
to. A copy of the Declaration of Helsinki may be located on the internet at: http://www.wma.net. 
17.1 Institutional Review Board (IRB) / Independent Ethics Committee (IEC) 
Before implementing this study, the protocol, the proposed informed consent form and other 
information that will be provided to Patients must be reviewed by an IRB/IEC. A signed and dated 
statement that the protocol, informed consent has been approved by the IRB/IEC must be provided 
to the Sponsor or its representative before study initiation.  Any amendment(s) to the protocol 
which need formal approval (such as sample size adjustment), as required by local law, will be 
approved by the IRB/IEC. The IRB/IEC should be notified in writing of all other amendment(s) 
(i.e., administrative changes).  
17.2 Informed Consent 
The principles of Informed Consent, according to the Declaration of Helsinki and its updates, ICH 
guidelines on GCP and EU Directives, will be followed. A Patient should not enter a clinical study 
until he/she has been properly informed, has been given time to contemplate participation, and has 
freely given his/her consent by signing and dating the IRB/IEC-approved Informed Consent Form.   
This must be done prior to performing any study-related procedures. The proposed consent form 
and any other documents relevant to the consent process must be submitted to the IRB/IEC, 
together with the protocol, and must be approved prior to study start.  
A copy of the fully signed and dated Informed Consent Form and any other documents relevant to 
the consent process will be given to the Patient and the original will be maintained at the site.  
The Investigator must explain to each Patient (or legally authorized representative) the nature of 
the study, its purpose, the procedures involved, the expected duration, the potential risks and 
benefits involved and any discomfort it may entail. Each Patient must be informed that 
participation in the study is voluntary and that he/she may withdraw from the study at any time 
and that withdrawal of consent will not affect his/her subsequent medical treatment or relationship 
with the treating physician.  
This informed consent should be given by means of a standard written statement, written in non-
technical language. The Patient should read and consider the statement before signing and dating 
it and should be given a copy of the signed document. If the Patient cannot read or sign the 
documents, oral presentation may be made or signature given by the Patient’s legally appointed 
representative, if witnessed by a person not involved in the study, mentioning that the Patient could 
not read or sign the documents.  
No Patient can enter the study before his/her informed consent has been obtained. The informed 
consent form is considered to be part of the protocol and must be submitted by the Investigator 
with it for IRB/IEC approval. 
17.3 Patient Confidentiality 
All Patient data will be identified only by a Patient identification number and Patient initials or 
Patient dummy initials and date of birth in accordance with local regulations. After obtaining 

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Patient’s consent, the Investigator will permit the study monitor, independent auditor or regulatory 
agency personnel to review that portion of the Patient’s medical record that is directly related to 
the study. This shall include all study relevant documentation including Patient medical history to 
verify eligibility, laboratory tests results, admission/discharge summaries for hospital admissions 
occurring while the Patient is on study, and autopsy reports for deaths occurring during the study 
(if applicable). 
 
18.  DATA HANDLING AND RECORD KEEPING 
18.1 Data Management Responsibilities 
Data are entered in a validated database. The internal consistency and data integrity of the study 
database are defined by a validated set of checks defined and documented in the Study Validation 
Plan. A deviation from this set of pre-defined computerized checks creates a discrepancy which 
can be handled using the Clinical Data Management System application. Data queries will be 
generated and resolved. Adverse events will be coded with MedDRA version 19.0 and 
concomitant therapies with WHO-DD version of December 2011. 
18.2 Electronic Data Capture Methods 
Electronic CRF is used to record study data and it is an integral part of the study and subsequent 
reports. Therefore, the eCRF must be completed for each Patient included in the study. Each 
Patient will be given a specific Patient number. Patient data will be recorded in the eCRF using 
this number and will not be known in any other way to any person other than the parties involved 
in conducting and regulating the study. 
18.3 Schedule and Content of Reports 
A final Clinical Study Report will be prepared according to ICH E3 Guidelines. 
18.4 Study Records Retention 
The Investigator will maintain all study records according to ICH-GCP and applicable regulatory 
requirements. Records will be retained for at least two years after the last marketing application 
approval or two years after formal discontinuation of the clinical development of the 
investigational product or according to applicable regulatory requirements. If the Investigator 
withdraws from the responsibility of keeping the study records, custody must be transferred to a 
person willing to accept the responsibility. 
18.5 Protocol Deviations 
Any not purely formal, significant change of the approved protocol will be documented and 
explained. As soon as possible, the implemented deviation or change, the reasons for it, and, if 
appropriate the proposed protocol amendment(s) will be submitted: 
• to the IRB/IEC for review and approval/favorable opinion, 
• to the Sponsor for agreement, and 
• to the regulatory authorities, if needed. 
 
The Investigator will implement a deviation from or a change of the protocol to eliminate 
immediate hazards to the trial Patients without prior approval/favorable opinion of the IRB/IEC.  
 

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19.  USE OF INFORMATION AND PUBLICATION 
All information obtained during the course of this study will be regarded confidential and the 
property of the Sponsor. The Investigators agree not to disclose such information in any way 
without prior written permission from the Sponsor. 
The information obtained from the clinical study will be disclosed to regulatory authorities, other 
Investigators, corporate partners, or consultants as required. 
The clinical study is planned to be registered on clinicaltrials.gov public database within 1 month 
after study start and to be kept updated throughout the entire study period. 
 
20.  REFERENCES 
 
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major surgical procedures: a cost analysis of 1200 Patients. Ann Surg. 2011;254:907–913. 
3. Spotnitz WD, Burks S. Haemostats, sealants, and adhesives: components of the surgical 
toolbox. Transfusion. 2008;48:1502–1516. 
4. Seyednejad H, Imani M, Jamieson T, Seifalian AM. Topical hemostatic agents. Br J Surg. 
2008;95:1197–1225. 
5. Sundaram CP, Keenan AC. Evolution of hemostatic agents in surgical practice. Indian J Urol. 
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6. Fok M, Ah-Chong, AK,  Cheng SWK,  Wong J ,  Comparison of a single layer continuous 
hand –swen method  and circular stapling in 580 oesophageal anastomoses.  Br J Surg 78: 342-
345m 1991 
7. 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 
8. Lane DA, Phillippou H, Huntington JA, Directing thrombin, BLLOAW 106.8: 2605-2612,  
2005  
9. Tanaka KA, Taketomi T, Szlam F, Calatzis A, and Levy JH., Improved clot formation by 
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10. Wheat JC and Wolf JS, Advances in bioadhesives, tissue sealants and hemostatic agents, Urol 
Clin N Am 36: 265-275, 2009. 
11. 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 Feb 2. 
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12. David Randall D et al. 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.