A Prospective, Multicenter, Randomized Clinical Investigation Evaluating the Safety and Efficacy of GATT-Patch Versus TachoSil for Hemostasis During Open Liver Surgery
Phase: NA
Conditions: Intraoperative Bleeding, Hemorrhage, Surgical, Liver Diseases
Sponsor: GATT Technologies BV

16.1.1 
Clinical Investigation Plan 
The latest version of the clinical investigation plan used during the trial is provided in this 
section. Previous versions of the clinical investigation plan are available on request. 
Clinical Investigation Plan DHF-01-SFT-194 Version 8 dated 08-August-2023 
 
Page 1 of 94

CLINICAL INVESTIGATION PLAN 
 
 
 
GATT Technologies BV 
Clinical Investigation Plan Title: A Prospective, Multicenter, Randomized Clinical 
Investigation Evaluating the Safety and Efficacy of GATT-Patch versus TachoSil for 
Hemostasis during Open Liver Surgery 
Clinical investigation plan Number: DHF-01-SFT-194 
Short Title: GATT-Patch versus TachoSil in Liver Surgery 
 
IDE Number: 
G210325 
EUDAMED Number: 
CIV-22-06-039767 
Name of Investigational Device: 
GATT-Patch 
UDI Number: 
87202993601GATTPATCH49 
Phase of Development: 
Pivotal 
Indication: 
Hemostasis 
Sponsor: 
Stuart Head, MD, PhD 
Chief Medical Officer, GATT Technologies BV 
Novio Tech Campus 
Transistorweg 5 
6534 AT Nijmegen 
The Netherlands 
Tel: 
+31 (0) 6 45306042 
Email: s.head@gatt-tech.com 
Clinical Investigation Plan 
Version:  
8 
 
Clinical Investigation Plan Date: 
08-August-2023 
 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to GATT 
Technologies BV. Any unauthorized copying or use of this document is prohibited. 
Page 2 of 94

CLINICAL INVESTIGATION PLAN APPROVAL SIGNATURES
Clinical Investigation Plan Title:
A Prospective, Multicenter, Randomized Clinical 
Investigation Evaluating the Safety and Efficacy of 
GATT-Patch versus TachoSil for Hemostasis during 
Open Liver Surgery
Clinical Investigation Plan Number: DHF-01-SFT-194
This study will be conducted in compliance with the clinical study Clinical Investigation Plan 
(and amendments), ISO14155 (Clinical Investigation for Medical Devices for Human 
Subjects Good Clinical Practice, and applicable regulatory requirements.
Sponsor Signatory
Stuart J. Head, MD, PhD
Chief Medical Officer, GATT Technologies 
BV
Signature
Date (DD-Mmm-YYYY)
Principal or Coordinating Investigator 
Professor James V. Guarrera, MD, FACS
Rutgers New Jersey Medical School
New Jersey, United States of America
Signature
Date (DD-Mmm-YYYY)
Professor dr. J. Hans W. de Wilt, MD, PhD
Radboud UMC
Nijmegen, The Netherlands
______________________________________
___ Signature
-
______________________________________
___ Date (DD-Mmm-YYYY)
Biostatistician and/or Medical Monitor
Alastair Smith, MD
Medical Monitor 
Syneos Health
Signature
Date (DD-Mmm-YYYY)
Page 3 of 94

INVESTIGATOR SIGNATURE PAGE 
Clinical Investigation Plan Title: 
A Prospective, Multicenter, Randomized Clinical 
Investigation Evaluating the Safety and Efficacy of 
GATT-Patch versus TachoSil for Hemostasis during 
Open Liver Surgery 
 
Clinical Investigation Plan Number: DHF-01-SFT-194 
 
Confidentiality and Current Good Clinical Practice ISO14155 (ISO14155 Clinical 
Investigation of Medical Devices for Human Subjects Good Clinical Practice)/ 
Compliance Statement ISO14155 for medical device studies 
 I, the undersigned, have reviewed this Clinical Investigation Plan (and 
amendments<as applicable>), including appendices, and I will conduct the study as 
described in compliance with this Clinical Investigation Plan (and amendments), 
ISO14155 and relevant International Council for Harmonization (ICH) guidelines. 
 I am thoroughly familiar with the appropriate use of the study device, as described in 
this Clinical Investigation Plan and any other information provided by GATT 
 
 Once the Clinical Investigation Plan has been approved by the independent ethics 
committee (IEC)/institutional review board (IRB), I will not modify this Clinical 
Investigation Plan without obtaining prior approval of GATT Technologies and of the 
IEC/IRB. I will submit the Clinical Investigation Plan amendments and/or any 
informed consent form modifications to GATT Technologies and the IEC/IRB, and 
approval will be obtained before any amendments are implemented. 
 I ensure that all persons or party assisting me with the study are adequately qualified 
and informed about the GATT Technologies investigational device GATT-Patch and 
of their delegated study-related duties and functions as described in the Clinical 
Investigation Plan. 
 I ensure that source documents and trial records that include all pertinent observations 
e attributable, legible, contemporaneous, 
original, accurate, and complete. 
 I understand that all information obtained during the conduct of the study with regard 
will be disclosed. All subjects will be identified by assigned numbers on all case 
report forms, laboratory samples, or source documents forwarded to the Sponsor. 
Clinical information may be reviewed by the Sponsor or its agents or regulatory 
agencies. Agreement must be obtained from the subjects before disclosure of subject 
information to a third party. 
 Information developed in this clinical study may be disclosed by GATT Technologies 
to other clinical investigators, regulatory agencies, or other health authority or 
government agencies as required. 
Page 4 of 94

<Name> 
 
<Title> 
Investigator Signature 
 
 
 
Date (DD-Mmm-YYYY) 
 
 
Institution 
 
 
 
 
Page 5 of 94

1. SYNOPSIS 
Title of Study: 
A Prospective, Multicenter, Randomized Clinical Investigation Evaluating the 
Safety and Efficacy of GATT-Patch versus TachoSil for Hemostasis during Open 
Liver Surgery 
Clinical Investigation Plan 
Number: 
DHF-01-SFT-194 
Investigators/Study Sites: 
A maximum of 12 sites in the United States and Europe, with a target number of 
sites of 4-7 in the US, 2-4 in The Netherlands, and 2-4 in Germany. The clinical 
investigation in the US will be limited to 2 US sites; expansion to further sites in 
the US will be covered in an IDE supplement, which will be submitted to FDA 
after enrollment of 10 US subjects. This report may also be provided to other 
local country authorities upon request. 
Phase of Development: 
Pivotal 
Objectives: 
The objective of this clinical investigation is to compare the safety and efficacy of 
GATT-Patch versus TachoSil in liver surgery  
Study Endpoints: 
Primary endpoint: The primary efficacy endpoint is defined as non-inferiority of 
GATT-Patch compared to TachoSil in the percentage of cases achieving 
hemostasis at 3 minutes without rebleeding at the 10-minute time point. 
Hemostasis will be defined by a grade of 0 (None/Dry) on the Surface Bleeding 
Severity Scale (SBSS). 
Secondary efficacy endpoints: 
 
Median time to hemostasis (seconds); 
 
Kaplan-Meier estimated distribution of time to hemostasis; 
 
Treatment failure, defined as no hemostasis at 10 minutes; 
 
Rebleeding after 10 minutes but before subject closure; and 
 
Percentage of hemostasis at 30, 60, 90, 120, 150, 180, 210, 240, 270, 
300, 360, 420, 480, 540, and 600 seconds. 
 
Safety endpoints: The safety of GATT-Patch will be assessed by the incidence, 
severity and relation to hemostatic device of all adverse events. The adverse 
events for the GATT-Patch group will be compared to those for the TachoSil 
group. Adverse events of special interest are bleeding-related events, 
thromboembolic events, biloma, and allergic reaction. 
 
Exploratory endpoints: 
 
Procedure duration (minutes); 
 
Estimated blood loss (mL) during surgery;  
 
Number and type of blood transfusions during hospitalization; 
 
Duration of Intensive Care Unit (ICU) stay; 
 
Total hospitalization time; 
 
Postoperative drainage volume, characteristics, and duration;  
 
Need for and cause of reoperation; 
 
Imaging of the liver resection at 6 weeks post-surgery to detect (1) fluid 
collection and its size (in mL) and aspect, (2) pseudo-aneurysm, (3) 
patch encapsulation, and (4) rolling up of the device on the resection 
plane; 
 
Amount of hemostatic material needed versus bleeding surface; 
 
User satisfaction (questionnaire) for GATT-Patch;  
 
Physician treatment preference assessment (questionnaire); 
 
Local recurrence of liver cancer at the resection; 
 
Cancer-free survival; and 
 
Overall survival. 
Study Design: 
This is a pre-market, prospective, randomized (2:1), multicenter, multi-national 
pivotal clinical investigation  
Page 6 of 94

Selection of Subjects: 
Main Inclusion Criteria: 
A subject must meet all of the following pre-operative inclusion criteria to be 
enrolled into the clinical investigation: 
1. 
Subject is scheduled to undergo elective open surgery on the liver; 
2. 
Subject is willing and able to give written informed consent for the 
clinical investigation participation; 
3. 
Subject is 22 years of age or older at the time of enrollment; and 
4. 
Subject has been informed of the nature of the clinical investigation. 
A subject must meet all of the following intra-operative inclusion criteria to be 
enrolled into the clinical investigation: 
1. 
Subject in whom the Investigator is able to identify a target bleeding 
site at the liver resection plane for which any applicable conventional 
means for hemostasis (e.g. suture, ligature or cautery) are ineffective or 
impractical, and the choice is made to use a hemostatic agent to stop the 
bleeding; and 
2. 
Subject has a target bleeding site with a SBSS of 1, 2, or 3 (e.g. 
reflecting minimal, mild or moderate bleeding severities). 
Main Exclusion Criteria: 
A subject must not meet any of the following pre-operative exclusion criteria to 
be enrolled into the clinical investigation: 
1. 
The target bleeding site is from a large defect in an artery or vein that 
requires vascular reconstruction with maintenance of vessel patency; 
2. 
Subject is scheduled to undergo surgery on other organs than the liver 
and its associated biliary and vascular system; 
3. 
Subject is scheduled to undergo a staged liver surgery procedure (e.g., 
Associating Liver Partition and Portal vein ligation for Staged 
hepatectomy [ALPPS]) 
4. 
Subject is taking multiple antithrombotic therapies in therapeutic 
dosage up to the time of surgery, but allowing exclusive use of 
acetylsalicylic acid; 
5. 
Subject has platelet count <100 x 109/L, an activated partial thrombin 
time of >100s, or international normalized ratio >2.5; 
6. 
 
7. 
Subject is pregnant, planning on becoming pregnant or actively 
breastfeeding during the 3-month follow-up period; 
8. 
Subject has a known hypersensitivity to brilliant blue (FD&C Blue #1), 
porcine gelatin, or horse proteins; 
9. 
Subject who has religious objections to receiving products with 
components of animal (porcine or equine) or human origin; 
10. Subject has an active or suspected infection at the bleeding site; 
11. Subject in whom the investigational device will be used at the site of a 
synthetic graft or patch implant;  
12. Subject has a life expectancy of less than 3 months; 
13. Subject has a documented severe congenital or acquired 
immunodeficiency;  
14. Subject has had or has planned to receive any organ transplantation; 
15. Subject is currently participating or has participated in another clinical 
investigation within the past 30 days that may affect the endpoints of 
the study, such as trials related to the surgical procedure, and on anti-
coagulation; 
16. Subject is not appropriate for inclusion in the clinical investigation, per 
the medical opinion of the Investigator; and 
17. Subject has any incidental (pre- and peri-operative) findings deemed by 
the Investigator to potentially jeopardize the safety or welfare of the 
subject.  
Withdrawal Criteria: 
 
Change in SBSS to ineligible (SBSS of 0, 4, or 5) between point of 
randomization and application of the hemostatic patch  
 
Death of subject in the time between randomization and patch use 
Planned Sample Size: 
Sample size of 130 subjects of which a total of 87 subjects will undergo 
implantation of GATT-Patch. 
Page 7 of 94

Investigational Device:  
GATT-Patch is a hemostatic patch with dimensions of 100x50 mm, which 
consists of a gelatin patch that is impregnated with a granulate of N-
Hydroxysuccinimide (NHS) ester-functional poly(2-ethyl-2-oxazoline) polymer 
(NHS-POx) and a nucleophilic amine-functional poly(2-ethyl-2-oxazoline) 
polymer (NU-POx) particles also referred to as P(EtOx-NH2) polymer. 
GATT-Patch will be applied onto the wound site where the flexible and 
resorbable gelatin patch is activated by tissue contact and initiates the coagulation 
solid elements leading to a matrix for platelet aggregation and release of 
coagulation factors enabling fibrin formation 'trapped' in the gelatin fibers. Once 
the patch is activated, via the combination of P(EtOx-OH-NHS), P(EtOx-NH2) 
and gelatin, a POx-hydrogel is formed. This POx-hydrogel has two effects: 
firstly, to adhere the patch to the tissue and secondly to form a seal across the 
damaged tissue. Both parts together help to ensure that high efficacy hemostasis 
can be achieved.  
Reference Device: 
TachoSil is a fibrin sealant patch indicated for use with manual compression in 
adult and pediatric patients as an adjunct to hemostasis in cardiovascular and 
hepatic surgery, when control of bleeding by standard surgical techniques (such 
as suture, ligature or cautery) is ineffective or impractical. 
TachoSil is a topical fibrin sealant patch consisting of human fibrinogen and 
human thrombin coated onto an equine collagen sponge.  
Reduction of bias: 
Due to the physical differences in the investigational and control devices, 
blinding of the surgeon is not possible. However, bias is minimized by using a 
validated bleeding scale to determine baseline bleeding severity prior to 
randomization, at which point in time the investigator is not aware of treatment 
assignment. Further, the training and testing required for all investigators to use a 
validated bleeding severity scale for assessment of successful hemostasis reduces 
subjectivity for the efficacy assessments. 
The following additional measures have been implemented to reduce potential 
bias in the assessment of safety and efficacy: 
 
Blinding patients to the randomized and received treatment;  
 
An independent adjudication committee will review all serious adverse 
events (SAEs) and adverse events of special interest (e.g., bleeding-
related events, thromboembolic events, biloma, and allergic reaction) 
occurring during the 3-month follow-up after surgery for relatedness to 
the device and expectedness of the event based on the clinical scenario 
comprising of patient and procedural characteristics; and 
 
A blinded independent data monitoring committee will review the 
overall safety and efficacy of the trial. 
Treatment Duration: 
The enrollment period is expected to take approximately 12 months, which 
includes an FDA review of data for the first 10 US subjects. This report will also 
be made available to other local country authorities for review upon request. The 
per subject duration of the clinical investigation from treatment to follow-up will 
be approximately 3 months. A full study report will be written based on the 3 
month follow-up data and will be submitted to all relevant local country 
authorities, including a pre-market approval submission to FDA.  
The total expected duration of the clinical investigation until PMA submission is 
approximately 15 months.  
Five-year observational follow-up will furthermore be performed on all patients 
undergoing liver resection for liver malignancy or metastases. This observational 
follow-up will not be in direct contact with the patient, but through electronic 
health records and/
 
Page 8 of 94

Arms and Interventions: 
This is a randomized clinical trial. GATT-Patch and TachoSil will be used to 
control bleeding during liver surgery. Each surgery will be performed according 
to the standard procedures of the hospital, with exception of the use of GATT-
Patch versus TachoSil. Furthermore, during the week 6 follow-up, imaging as 
well as some laboratory test may be considered study specific assessments. 
Subjects who signed informed consent, who meet the preoperative eligibility 
criteria, and who have an appropriate bleeding site (SBSS 1, 2 or 3 and no 
contraindications) will be randomized between GATT-Patch and TachoSil in a 
ratio of 2:1. Randomization will be performed intra-operatively, after intra-
operative eligibility criteria have been confirmed. GATT-Patch and TachoSil 
application will be according to their instructions for use, with 30 seconds of 
pressure for GATT-Patch and 3 minutes of pressure for TachoSil. If GATT-Patch 
or TachoSil does not result in hemostasis, rescue therapy with additional surgical 
techniques and/or hemostatic agents is allowed.  
Statistical Methods and Planned 
Analyses: 
 
This study will include an FDA review of data for the first 10 US-based 
patients from 2 US-based sites. No formal statistical analyses will be 
performed on these data. The data will also be made available to other local 
country authorities for review upon request. After FDA approval to continue, 
the study utilizes an adaptive design with an interim analysis planned for the 
purposes of stopping the trial early for success and for sample size re-
estimation. The interim analysis will be performed once 70% (n=91) of the 
planned evaluable subjects in total are treated. 
 
Descriptive statistics will be presented for each variable. Continuous 
variables will be summarized by treatment group using number of subjects, 
mean, median, standard deviation, minimum, and maximum. Categorical 
variables will be summarized by treatment group using frequencies and 
percentages of subjects in each category. For time-to-event, a Kaplan-Meier 
plot will be presented, and 25%, 50%, and 75% percentiles and their 95% 
confidence intervals will be reported. 
 
The primary analysis of the primary efficacy endpoint will be conducted 
using the Farrington-Manning test on the Per-Protocol (PP) population with 
available data. The primary efficacy endpoint will also be analyzed on the 
Intent-to-Treat (ITT) population as a secondary analysis. The key secondary 
endpoint of median time-to-hemostasis will be analyzed using a one-sided 
Wilcoxon-Mann-Whitney test. Other secondary endpoints, and exploratory 
and safety endpoints will be summarized descriptively. 
Page 9 of 94

2. TABLE OF CONTENTS 
 
1. 
SYNOPSIS ...................................................................................................................................... 5 
2. 
TABLE OF CONTENTS ................................................................................................................ 9 
2.1. 
List of In-text Tables .................................................................................................................13 
2.2. 
List of In-text-Figures ................................................................................................................14 
3. 
LIST OF ABBREVIATIONS........................................................................................................15 
4. 
INTRODUCTION .........................................................................................................................17 
4.1. 
Background on Liver Surgery ...................................................................................................17 
4.2. 
Background on Hemostatic Agents used during Liver Surgery ................................................17 
4.3. 
Background on GATT-Patch .....................................................................................................18 
4.4. 
Regulatory Classification ...........................................................................................................19 
4.5. 
Materials ....................................................................................................................................19 
4.6. 
Nonclinical Studies ....................................................................................................................20 
4.7. 
Clinical Studies ..........................................................................................................................21 
4.8. 
Clinical Risks/Benefits of the GATT-Patch ..............................................................................22 
4.8.1. 
Risk associated with GATT-Patch .........................................................................................22 
4.8.2. 
Risks associated with participating in the clinical investigation ...........................................23 
4.8.3. 
Risk control/migration ...........................................................................................................24 
4.8.4. 
Benefits ..................................................................................................................................24 
4.8.5. 
Potential benefits ...................................................................................................................24 
4.8.6. 
Benefit-risk rationale .............................................................................................................24 
4.9. 
Study Rationale ..........................................................................................................................25 
5. 
STUDY OBJECTIVES AND ENDPOINTS.................................................................................26 
5.1. 
Objectives and Hypotheses of the Clinical Investigation ..........................................................26 
5.2. 
Study Endpoints .........................................................................................................................26 
5.2.1. 
Primary Efficacy Endpoint ....................................................................................................26 
5.2.2. 
Secondary Endpoints .............................................................................................................27 
5.2.2.1. 
Efficacy Endpoints .............................................................................................................27 
5.2.2.2. 
Safety Endpoints ................................................................................................................27 
5.2.2.3. 
Exploratory Endpoints .......................................................................................................27 
5.2.2.4. 
Five-year follow-up ...........................................................................................................28 
6. 
INVESTIGATIONAL PLAN ........................................................................................................29 
6.1. 
Description of Overall Study Design and Plan ..........................................................................29 
6.2. 
Rationale for endpoint selection ................................................................................................30 
Page 10 of 94

6.3. 
Discussion of Study Design .......................................................................................................32 
6.4. 
End of Study ..............................................................................................................................32 
7. 
SELECTION OF STUDY POPULATION ...................................................................................34 
7.1. 
Inclusion Criteria .......................................................................................................................34 
7.2. 
Exclusion Criteria ......................................................................................................................34 
7.3. 
Rescreening ................................................................................................................................35 
7.4. 
Study Withdrawal, Removal, and Replacement of Subjects .....................................................35 
7.5. 
Investigational Sites ...................................................................................................................36 
7.6. 
Suspension or Premature Termination of the Clinical Investigation .........................................37 
8. 
TREATMENTS .............................................................................................................................38 
8.1. 
Details on the Investigational device .........................................................................................38 
8.1.1. 
Contradictions ........................................................................................................................38 
8.1.2. 
Warnings ................................................................................................................................38 
8.1.3. 
Precautions .............................................................................................................................39 
8.1.4. 
Administration .......................................................................................................................39 
8.1.5. 
Handling in the Clinical Trial ................................................................................................40 
8.2. 
Details on the control product ....................................................................................................41 
8.3. 
Surgical procedure .....................................................................................................................42 
8.4. 
Measures to Minimize Bias .......................................................................................................45 
8.5. 
Device Accountability and Compliance ....................................................................................45 
8.5.1. 
Device Accountability ...........................................................................................................45 
8.6. 
Prior and Concomitant Therapy/Medication .............................................................................46 
9. 
STUDY PROCEDURES ...............................................................................................................47 
9.1. 
Informed Consent ......................................................................................................................48 
9.2. 
Study Procedures .......................................................................................................................48 
10. 
CLINICAL PERFORMANCE ASSESSMENTS .....................................................................48 
10.1. 
Surface Bleeding Severity Scale (SBSS) ...............................................................................49 
10.2. 
Investigational Device and Procedure ...................................................................................49 
11. 
SAFETY ASSESSMENTS .......................................................................................................51 
11.1. 
Medical History .....................................................................................................................51 
11.2. 
Physical Examination ............................................................................................................51 
11.3. 
Laboratory Assessments ........................................................................................................52 
11.4. 
Equipment for Assessment ....................................................................................................54 
11.5. 
Adverse Events ......................................................................................................................54 
11.5.1. 
Adverse Events ......................................................................................................................54 
11.5.2. 
Adverse Device Effect ...........................................................................................................56 
Page 11 of 94

11.5.3. 
Device Deficiency .................................................................................................................56 
11.5.4. 
Adverse Events of Special Interest ........................................................................................56 
11.5.5. 
Foreseeable Adverse Events and Anticipated Adverse Device Effects .................................57 
11.5.6. 
Serious Adverse Events .........................................................................................................57 
11.5.7. 
Serious Adverse Event and Adverse Event Reporting ..........................................................58 
11.5.8. 
Serious Adverse Device Effect ..............................................................................................59 
11.5.9. 
Unanticipated Serious Adverse Device Effects/ Unanticipated Adverse Device Effects .....59 
11.5.10. 
Pregnancy ..........................................................................................................................60 
11.6. 
Independent Adjudication Committee ...................................................................................60 
12. 
STATISTICAL ANALYSIS .....................................................................................................61 
12.1. 
Study Hypothesis ...................................................................................................................61 
12.2. 
Determination of Sample Size ...............................................................................................61 
12.3. 
Analysis Population ...............................................................................................................62 
12.4. 
Efficacy Analysis ...................................................................................................................62 
12.5. 
Safety Analysis ......................................................................................................................63 
12.6. 
Other Analysis .......................................................................................................................64 
12.6.1. 
Subgroup Analysis .................................................................................................................64 
12.6.2. 
Interim Analysis.....................................................................................................................64 
12.6.3. 
Five-year follow-up ...............................................................................................................65 
12.7. 
Independent Data Monitoring Committee .............................................................................65 
13. 
STUDY MANAGEMENT ........................................................................................................67 
13.1. 
Approval and Consent ...........................................................................................................67 
13.1.1. 
Regulatory Guidelines ...........................................................................................................67 
13.1.2. 
Institutional Review Board/Independent Ethics Committee .................................................67 
13.1.3. 
Informed Consent ..................................................................................................................67 
13.2. 
Data Handling ........................................................................................................................67 
13.2.1. 
Source Documents .................................................................................................................68 
13.2.2. 
Record Retention ...................................................................................................................68 
13.3. 
Monitoring .............................................................................................................................69 
13.4. 
Quality Control and Quality Assurance .................................................................................69 
13.5. 
Clinical Investigation Plan Amendment and Clinical Investigation Plan Deviation .............69 
13.5.1. 
Clinical Investigation Plan Amendment ................................................................................69 
13.5.2. 
Clinical Investigation Plan Deviations ..................................................................................70 
13.6. 
Ethical Considerations ...........................................................................................................70 
13.7. 
Financing and Insurance ........................................................................................................70 
13.8. 
Publication Policy/Disclosure of Data ...................................................................................70 
Page 12 of 94

14. 
REFERENECES ........................................................................................................................72 
15. 
APPENDICES ...........................................................................................................................74 
15.1.1. 
APPENDIX 1. User satisfaction questionnaire .....................................................................75 
15.1.2. 
Physician Treatment Preference Assessment ........................................................................84 
15.1.3. 
APPENDIX 3. Surface Bleeding Severity Scale (SBSS) Training and Testing ...................87 
15.1.4. 
APPENDIX 4. Safety Reporting Germany ...........................................................................88 
15.1.5. 
APPENDIX 5. Safety Reporting The Netherlands ................................................................89 
 
Page 13 of 94

2.1. List of In-text Tables 
Table 1. Summary of Hemostatic Trials in Liver Surgery ....................................................................17 
Table 2. Raw Materials/Chemical Components GATT-Patch ..............................................................19 
Table 3. Alternative Hemostatic Products .............................................................................................20 
Table 4: Summary of Primary Endpoint Outcome reported in Scientific Literature and Used in Sample 
Size Calculation .....................................................................................................................................30 
Table 5. Number of Clinical Sites per Geography ................................................................................36 
Table 6. Surface Bleeding Severity Scale ..............................................................................................42 
Table 7. Schedule of assessments ..........................................................................................................47 
Table 8. Laboratory Testing Schedule ...................................................................................................52 
Table 9. Classification of Adverse Events by Severity .........................................................................54 
Table 10. Classification of Adverse Events by Relationship to Study Device ......................................55 
 
Page 14 of 94

2.2. List of In-text-Figures 
Figure 1. 
GATT-Patch ......................................................................................................................19 
Figure 2. 
Sequence of Events for Enrollment, Hemostatic Assessments and Time Points. .............26 
Figure 3. 
Study Design ......................................................................................................................29 
Figure 4. 
GATT Application Flowchart ............................................................................................41 
Figure 5. 
GATT-Patch Training Flow Chart .....................................................................................50 
 
 
Page 15 of 94

3. LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE  
Anticipated Serious Adverse Device Effect 
CFR 
Code of Federal Regulations 
CIP 
Clinical Investigation Plan 
CTCAE 
Common Terminology Criteria for Adverse Events 
IDMC 
Independent Data Monitoring Committee 
(e)CRF 
(electronic) Case Report Form 
EDC 
Electronic Data Capture 
eGFR 
estimated Glomerular Filtration Rate 
EU 
European Union 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FD&C 
Federal Food, Drug, and Cosmetic Act 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IAC 
Independent Ajudication Committee 
IB 
 
ICF 
Informed Consent Form 
ICU / IC 
Intensive Care Unit / Critical Care Unit 
IDE 
Investigational Device Exemption 
IDMC 
Independent Data Monitoring Committee  
IEC 
Independent Ethics Committee 
IFU 
Instructions For Use 
IRB 
Institutional Review Board 
ISO 14155 
International Standard on the Clinical investigation of medical devices for human subjects 
 
Good clinical practice 
ITT 
Intention-to-treat 
MDR 
Medical Device Regulation 
MedDRA 
Medical Dictionary for Regulatory Activities 
NHS-POx 
N-hydroxysuccinimide ester (NHS)-functional poly(2-oxazoline)s  
NU-POx 
Nucleophilically Activated Polyoxazoline 
ORC 
Oxidized Regenerated Cellulose 
PI 
Principal Investigator 
Page 16 of 94

PP 
Per-protocol 
PEG 
Polyethylene glycol 
P(EtOx-NH2)  
nucleophilic amine-functional poly(2-ethyl-2-oxazoline) polymer (NU-POx) (polyoxazoline) 
P(EtOx-OH-NHS) 
N-Hydroxysuccinimide (NHS) Ester-Functionalized Poly(2-ethyl-2-oxazoline) 
Polymer (NHSPOx) (polyoxazoline) 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBSS 
Surface Bleeding Severity Scale 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
TBS 
Target Bleeding Site 
TEAE 
Treatment-Emergent Adverse Event 
TTH 
Time To Hemostasis 
TMF 
Trial Master File 
 
 
 
Page 17 of 94

4. INTRODUCTION  
 
4.1. Background on Liver Surgery 
Hepatic surgery, such as liver resection, has been associated with considerable mortality and 
morbidity.1 The postoperative mortality for major hepatectomy has been reported in a range 
from 0.7% to 2.6%.2 The short-term and long-term outcomes of open liver surgery may be 
influenced by uncontrolled bleeding during the operation, and a need for blood transfusion.1,2 
A 2011 retrospective analysis of approximately 1.6 million surgeries, including cardiac, 
vascular, solid organ, and spinal surgeries, found that the rate of bleeding-related 
complications was 29.9%, with blood transfusions occurring in 21.2% of all patients. There 
are significant benefits to patients when hemostasis is addressed efficiently, and effective 
treatment of bleeding may reduce blood loss and peri-operative complications.3  
During liver surgery, most luminal structures greater than 2 mm in diameter are controlled 
during parenchymal transection4 temporary occlusion of inflow vessels (e.g., Pringle 
maneuver to control inflow of the portal triad), and control of bleeding from outflow vessels 
(lowering central venous pressure or anterior elevation of the liver to avoid back-bleeding).4,5 
After transection, small volume bleeding may occur from the cut surface of the future liver 
remnant. Ligation, or electrocautery techniques can be used to control bleeding from visible 
compromised vessels. Bleeding from generalized venous ooze is better controlled with 
topical hemostatic agents. 
4.2. Background on Hemostatic Agents used during Liver Surgery 
Previous European and US-based studies performed with hemostatic agents used during liver 
surgery have demonstrated that the patient population is anticipated to be an adult population 
with a mean age of 60-65 years, predominantly white/Caucasian and approximately 37-48% 
being female (Table 1). In terms of disease and liver characteristics, the main indication for 
liver resection surgery was metastasis and the presence of cirrhosis is typically 2-10% (with 
one outlier). Moreover, trials including US sites have similar characteristics as trials with 
purely non-US-based sites. 
Included patients in the first-in-human clinical investigation (Section 4.7) were of a mean age 
of 59.7 years, 30% were female, and 91% being white/Caucasian. The indication for surgery 
was colorectal metastases in 66% of patients and 6% of patients had liver cirrhosis. The 
population as included in the first-in-human trial therefore represents a similar population as 
seen in other hemostatic trials in liver surgery, and the current pivotal trial is anticipated to 
include a similar patient population by including similar clinical sites. 
Further details on the expected hemostatic performance of approved agents is summarized in 
Section 6.2. 
Table 1. Summary of Hemostatic Trials in Liver Surgery 
Reference  
Study 
Design / 
Location(s) 
Hemostatic Agents  
and Population  
Age in 
years 
Female 
sex (%) 
Race 
Liver 
Cirrhosis 
(%) 
Main Surgical 
Indication 
Bjelovic et 
al., 2018  
RCT (1:1)  
FS Grifols vs Surgicel 
(n=325) 
Mean: 58 
48% 
Caucasian 
(91%) 
4% 
Unclear 
Page 18 of 94

Reference  
Study 
Design / 
Location(s) 
Hemostatic Agents  
and Population  
Age in 
years 
Female 
sex (%) 
Race 
Liver 
Cirrhosis 
(%) 
Main Surgical 
Indication 
US, Europe, 
Russia  
Bochicchio 
et al, 2015  
RCT (2:1)  
US and 
Europe 
Fibrocaps vs Gelatin sponge 
(n=181) 
 
Mean: 61 
37% 
White 
(95%) 
Not 
reported 
Not reported 
Fisher et al., 
2011  
RCT (1:1)  
Denmark  
TachoSil vs Argon 
Beam Coagulation (n=119) 
Mean: 60 
41% 
Not 
reported 
Excluded 
Not reported 
Genyk et al., 
2016  
RCT (1:1)   
US  
TachoSil vs ORC (n=224)  
 
Mean: 58  
47% 
Caucasian 
(79%) 
10% 
Malignant tumor (78%) 
with 49% metastatic 
Koea et al., 
2013  
RCT (1:1)  
Europe  
EVARREST vs 
Standard (n=88) 
Median: 
65  
43% 
Not 
reported 
8% 
Colorectal metastases 
(75%) 
Koea et al., 
2016  
RCT (1:1)  
Europe  
EVARREST vs 
Standard (n=102) 
 
Median: 
63-64 
39% 
Not 
reported 
9% 
Colorectal metastases 
(64%) 
Moench et 
al., 2014  
RCT (1:1)  
Germany  
TachoSil vs 
Sangustop (n=127) 
Mean: 62 
42% 
Not 
reported 
Excluded 
Liver metastasis (63% 
Ollinger et 
al., 2013 
RCT (2:1)  
Europe  
Veriset vs TachoSil (n=50) 
Mean: 62 
40% 
White 
(100%) 
2% 
 
Rahbari et 
al., 2020  
RCT (1:1)  
Germany  
BioFoam vs Standard 
(n=101) 
Mean: 63 
40% 
Not 
reported 
32% 
Metastatic malignancy 
(56%) 
RCT = randomized controlled trial 
4.3. Background on GATT-Patch 
GATT-Patch (Figure 1) is a sterile, flexible and resorbable hemostatic patch. It presents as a 
blue, soft, flexible, porcine gelatin fiber-based carrier impregnated with an NHS-POx/NU-
POx granulate. GATT-Patch measures 10 cm long by 5 cm wide. GATT Patch is active and 
can be applied on both sides. Blue color is an aid to visualize GATT Patch when applied onto 
a bleeding location. 
GATT-Patch will be applied to the wound site where the fibrous gelatin patch presents as an 
adjunct to hemostasis by tamponade effect and formation of a mechanical barrier. The fibrous 
gelatin matrix supports the intrinsic coagulation process by dehydrating the blood to capture 
and 
release of coagulation factors enabling fibrin formation 'trapped' in the gelatin fibers. Once 
GATT-patch is in contact with an aqueous environment, a POx-hydrogel is formed. This 
POx-hydrogel has two effects: (1) to adhere the fibrous gelatin carrier to the tissue and (2) to 
form a seal across the damaged tissue. Together, these two effects help ensure that highly 
effective hemostasis can be achieved by a mechanical barrier function. The time to 
hemostasis (TTH) is expected to be 30 seconds based on the instructions for use, and as 
confirmed in the first-in-human clinical investigation. 
GATT-Patch is a Class III medical device intended for application by trained physicians as an 
aid to hemostasis on internal organs during surgery after standard surgical hemostatic 
techniques have been applied. The effect is local and primarily mechanical and is not 
Page 19 of 94

dependent on the coagulation status of the patient. The product is not removed at the end of 
surgery but is resorbed in 4-6 weeks.a
Figure 1. 
GATT-Patch 
 
4.4. Regulatory Classification 
GATT-Patch is indicated for use as an adjunct to hemostasis in surgery for minimal, mild or 
moderate bleeding sites when control of bleeding by standard surgical techniques (such as 
suture, ligature or cautery) is ineffective or impractical. GATT-Patch is intended to be used 
for management of hemorrhage during surgeries on the liver. According to classification rule 
8 of Annex VIII of the EU MDR 4 April 2017, the device is a long-term surgically invasive 
and implantable device. The device will be wholly absorbed and it will undergo a chemical 
change in the body. 
According to classification rule 18 of Annex VIII of the EU MDR 4 April 2017, the device is 
manufactured utilizing derivatives of animal origin, which are non-viable or rendered non-
viable. 
Therefore, according to both classification rules, GATT-Patch is classified as a Class III 
medical device. 
4.5. Materials 
A listing of the raw materials used in the manufacturing of the final finished P(EtOx-OH-
NHS) - P(EtOx-NH2) granulate-based hemostatic patches is provided in Table 2. GATT 
Patch is an implant, and all components are in direct contact with the human body. 
Table 2. Raw Materials/Chemical Components GATT-Patch 
Device Component 
Raw Materials in 
Component 
Supplier 
CAS 
Number 
Polymers 
P(EtOx-OH-NHS) polymer 
PolyVation 
NA 
P(EtOx-NH2) polymer 
PolyVation 
NA 
Blue Colorant FD&C Blue #1 
FD&C Blue #1 
Spectrum Chem. via 
VWR 
3844-45-9 
 
a The resorption time was estimated 4-6 weeks based on initial preclinical testing of prototypes. The outcomes 
of a recent GLP implantation study on the final design of GATT-Patch shows resorption in <4 weeks. 
Page 20 of 94

Granulate 
P(EtOx-OH-NHS) and 
P(EtOx-NH2) 
GATT Technologies 
NA 
Porous Gelatin carrier (porcine 
origin) 
Gelatin 
Gelita Medical 
9000-70-8 
 
4.6. Nonclinical Studies 
GATT Technologies BV performed preclinical testing to assess residual risks associated with 
the device. In summary, a study on the use of GATT-Patch versus Surgifoam + Thrombin 
and Hemopatch in a porcine liver bleeding model was performed and demonstrated non-
inferior time to hemostasis with GATT-Patch versus controls, a lower local tissue reactivity 
than controls, no device migration through the abdominal cavity, no more intra-abdominal 
adhesions than with the control products, device degradation within 28 days, and no adverse 
events (AEs) up to 8 weeks of follow-up. Design verification and validation was performed 
in accordance with national and international standards. The outcomes of the pre-clinical tests 
demonstrated that the device performs as intended.  
A literature review was performed to establish clinical evidence referring to the clinical 
safety and performance, and associated risks and benefits of GATT-Patch (Literature Review 
Clinical Investigation Plan Version 01, 24 September 2020). The objective was to identify 
comprehensive and up-to-date information on established therapies, the safety and 
performance of state-of-the-art treatments and/or devices, methods to assess effectiveness, 
and known AEs that are related to the management of hemorrhage during liver surgery. 
Relevant outcomes included AEs, device deficiencies, study population (eligibility criteria), 
primary effectiveness/performance and safety outcome measures and secondary outcome 
measures. Overall, data obtained through the literature review was used to provide input to 
the assessment of acceptable benefit/risk profiles of GATT-Patch and to determine the 
performance goal for a proposed clinical investigation on GATT-Patch. A summary is 
provided below.  
There are numerous hemostasis products approved for bleeding during surgery (Table 3). 
This includes both biological and synthetic products as well as patches and non-patches. 
These products have different modes of action based on their composition, but despite 
differences in composition and formation (patch vs non-patch), many of these products have 
a similar indication as adjunct to hemostasis. These products are thus relevant to consider as 
alternatives to GATT-Patch. 
For the risk management activities, specific alternative patches that are approved for 
hemostasis in Europe, such as TachoSil, Veriset, and Hemopatch, and that have a similar 
mode of action and intended use as GATT-Patch, were used to provide input in the risk 
profile of GATT-Patch. 
Table 3. Alternative Hemostatic Products 
Category 
Class 
Mechanical 
Porcine gelatin 
Bovine collagen 
Oxidized regenerated cellulose (ORC) 
Active 
Bovine thrombin 
Page 21 of 94

Human-pooled plasma thrombin 
rhThrombin 
Combined 
Porcine gelatin + thrombin 
Bovine gelatin and human-pooled plasma thrombin 
Fibrin sealants 
Human plasma and human thrombin 
Human-pooled plasma and bovine thrombin 
Individual human plasma, bovine collagen and bovine thrombin 
Human-pooled plasma and equine collagen 
Synthetic sealants, PEG-based 
Two PEGs 
PEG, trilysine amine and FD&C Blue #1 
PEG and human serum albumin 
Albumin and glutaraldehyde 
Bovine serum albumin and 10% glutaraldehyde 
 
In general, topical hemostatic agents have been found effective to control bleeding at 
bleeding sites that include raw diffuse bleedings and that are difficult to control using 
traditional hemostatic techniques.1,2 GATT-Patch is intended to provide fast and persistent 
control of bleeding during surgeries on internal organs. When compared to other hemostatic 
agents that are considered standard of care or when compared to benchmark devices, it is 
expected that GATT-Patch will provide at least the same rate of hemostasis, but faster and 
with improved adhesion for a prolonged benefit. The flexibility and pliability of GATT-Patch 
allows it to be used in a variety of clinical situations where current standard of care patch 
products are impractical for use. Furthermore, the composition and mode of action of GATT 
Patch differentiates from currently approved products and thereby addresses the medical need 
of a combination of quick and persistent hemostasis and strong adhesion to the tissue. 
The risks of GATT-Patch are considered similar to other hemostats used during liver surgery 
(patch and non-patch). There is low risk of AEs associated with topical hemostatic agents.2 
Device-related AEs that were identified for benchmark devices (devices with similar 
properties and the same intended use as GATT Patch) occurred with a low incidence rate: 0 
to 18.2%, with 18.2% being a reported imbalance in treatment assignment to two 
investigators, who had a different interpretation of causal events than other investigators. If 
not taken into account, device-related AE occurred in a range of 0% to 6.7% and included the 
risk of bile leak, hematoma, anemia, diarrhea hypomagnesemia, localized intra-abdominal 
fluid collection, nausea, peritoneal abscess, pleural effusion, infectious peritonitis, liver 
abscess, postoperative abscess, postoperative adhesion and procedural hemorrhage. There is 
no risk of immunogenicity. One device-related event of increased C-reactive protein was 
identified (1.8%) but was considered non-serious. 
4.7. Clinical Studies 
In the Netherlands, a first-in-human, single-arm clinical investigation was conducted to 
confirm safety and efficacy of GATT-Patch. In patients undergoing open liver resection 
surgery, GATT-Patch was applied on the liver resection surface to initiate hemostasis for 
minimal, mild, or moderate bleeding in the case that standard surgical techniques were 
ineffective or impractical. After a preplanned initial safety enrollment cohort of 8 patients 
(Stage I), the Independent Data Monitoring Committee (IDMC) agreed to continue with an 
efficacy cohort (Stage II), on the basis of adequate safety. The success of GATT Patch was 
measured against a performance goal of 65.4%, which represents the lower bound of the 95% 
Page 22 of 94

confidence interval of a weighted mean number of patients who reach hemostasis within 3 
minutes with already approved hemostatic products during liver surgery. The results of the 
trial showed that the percentage of Stage II subjects that achieved hemostasis at 3 minutes 
using GATT-Patch was 97.4%, and was higher than the literature-based performance goal of 
65.4% (P<0.001). An additional analysis was performed on a per bleeding site basis, showing 
that the percentage of bleeding sites that achieved hemostasis at 3 minutes using GATT-Patch 
was 96.3% of the 54 bleeding sites treated during Stage II. In the trial, a total of 47 patients 
were treated with GATT-Patch on 63 target bleeding sites, and hemostasis at 3 minutes was 
achieved in 96.7% of the 63 bleeding sites.  
Furthermore, the entire enrolled cohort was evaluated for safety of GATT-Patch. A total of 
28 of the 47 subjects (59.6%) experienced AEs and 7 of the 47 subjects (14.9%) experienced 
serious AEs (SAEs). The incidence of device related AEs was 6.4% and the incidence of 
device related SAEs was 2.1%. Three of the 47 subjects experienced AEs that were related to 
both the device and procedure, all considered to be possibly related and there were no events 
with a probably or causal relationship with the device. These AEs involved one subject with 
biloma, one subject with a perihepatic abscess, and one subject with post-procedural 
hematoma. One of the 47 subjects experienced an SAE that was related to both the device 
and the procedure and involved a perihepatic abscess. The types and incidence of AEs seen 
for GATT-Patch are comparable to similar hemostatic products. 
The present pivotal clinical investigation is intended to investigate whether the device is safe 
and performs as intended when compared to TachoSil. 
This clinical investigation is intended to collect clinical safety and efficacy data to support 
marketing approvals in the United States and Europe. 
Clinical data from competitor devices and standard of care treatment for open liver surgery 
were reviewed and were used to predict safety and performance outcomes of GATT-Patch 
and to create appropriate preventive measures for possible risks associated with the device. 
All residual risks for GATT-Patch have been assessed and reduced to an acceptable or 
tolerable level, as confirmed in the pilot clinical investigation. To date, there have been no 
comparative clinical investigation assessing the safety and efficacy of GATT-Patch. 
Therefore, this clinical investigation is warranted. 
4.8. Clinical Risks/Benefits of the GATT-Patch 
4.8.1. Risk associated with GATT-Patch 
Possible risks for GATT-Patch were assessed and controlled using the EN-ISO 14971 
 
risk management are recorded in the risk management report. In summary, according to the 
resu
lerable and occasional to 
 
 
Toxic response 
 
Thromboembolic event 
 
(Re)Bleeding 
 
Allergic reaction 
 
New surgery 
Page 23 of 94

 
Infection (e.g., abscess) 
 
Blockage of artery or vein/ischemia of organs 
 
Damage of organs and vessels 
 
Adhesion to other organs  
 
(Pulsatile) hematoma 
 
Closing of intestinal track 
 
Biloma (e.g., bile leakage) 
Note: these events can be considered procedure- or device-related events. 
Furthermore, the risk for encapsulated or rolled-up device was identified during the risk 
management, at a lower risk level/incidence. This risk will be further investigated in this 
clinical investigation by means of the 6-weeks follow-up imaging.  
In the first-in-human clinical investigation, the following adverse events occurred with a 
possible relationship to the device: hematoma (n=1/47, 2.1%), biloma (n=1/47, 2.1%) and 
perihepatic abscess (n=1/47, 2.1%). There were no adverse events with a probable or causal 
relationship to the device. While other adverse events occurred, these were considered not 
related to the device. 
A full study report will be written based on the 3 month follow-up data and will be submitted 
to all relevant local country authorities, including a pre-market approval submission to FDA. 
Furthermore, 5 year observational follow-up will be performed to characterize long-term 
safety on all patients undergoing liver resection for liver malignancy or metastases, collecting 
data on local cancer recurrence, disease-free survival, and overall survival. This observational 
follow-up will not be in direct contact with patient, but through electronic health records 
 
4.8.2. Risks associated with participating in the clinical investigation 
Participation in this clinical investigation may also present additional risks or inconveniences, 
including, but not limited to: 
 
Procedure-related adverse events during open liver surgery similar to the standard of 
care 
 
Inconvenience related to ultrasound imaging conducted at 6 weeks postoperatively 
 
Follow-up visits/assessments at 6 and 12 weeks postoperative 
 
Other unforeseen risks 
Further, those patients randomized to receive TachoSil are subject to risks associated with use 
of that device, which could include: 
 
Anemia 
 
Nausea 
 
Vomiting 
 
Fever 
 
Abdominal pain 
 
Increase white blood cell count 
 
Ascites 
 
Itching 
 
Atrial fibrillation 
 
Pleural effusion 
Page 24 of 94

 
Gastrointestinal hemorrhage 
 
Wound infection 
 
Hypophosphatemia 
 
Urinary tract infection 
 
Post-procedural bile leak 
4.8.3. Risk control/migration 
GATT Technologies BV performed risk analysis in accordance with EN ISO 14971:2019. 
All residual risks have been controlled and are mitigated to an acceptable level. Careful 
definitions of specific eligibility criteria, study procedures and instructions for use, 
appropriate selection, qualification and training of the investigators, and patient follow-up 
procedures have been designed as to further contribute to reduce risks as far as possible for 
the patient and residual risk acceptance. 
Furthermore, potential risks associated with participation in this investigation will be 
minimized and managed in accordance with ISO 14155, and requirements of the approving 
IRBs and ECs. 
4.8.4. Benefits 
The intended clinical benefit of GATT-Patch is to provide fast and persistent hemostasis 
during surgeries on the liver. It is hypothesized that a high rate of fast and persistent 
hemostasis may result in less clinical risk of complications to patients undergoing these 
surgeries. 
4.8.5. Potential benefits 
It is anticipated that application of the investigational device to a target bleeding site will 
result in a reduced time to hemostasis compared to conventional methods of hemostasis, such 
as suture, ligature, or cautery.  Individual patients may not benefit directly from participation 
in this clinical investigation, but conducting this research could contribute to the overall 
advancement of medical and scientific knowledge and may benefit future patients. 
4.8.6. Benefit-risk rationale 
GATT Technologies BV believes that any potential risk presented by this clinical 
investigation has been minimized and that adequate testing, safeguards, and safety 
monitoring have been incorporated into the clinical investigation to further minimize and 
mitigate the risks. GATT Technologies BV believes that the potential benefits of GATT-
Patch outweigh the potential risks posed to participating subjects. This clinical investigation 
has been designed to involve as little pain, discomfort, fear and any other foreseeable risks as 
possible of the subjects. The risk threshold and degree of distress to subjects are defined in 
the risk analysis. 
Further, oversight of the clinical investigation will be provided by: 
 A blinded Independent Data Monitoring Committee (IDMC) will monitor the study to 
ensure safety of study participants and validity and integrity of the data. 
 An Independent Adjudication Committee (IAC) will review all serious adverse events 
(SAEs) and adverse events of special interest (e.g., bleeding-related events, 
thromboembolic events, biloma, and allergic reaction) occurring during the 3-month 
Page 25 of 94

follow-up after surgery for relatedness to the device and expectedness of the event 
based on the clinical scenario comprising of patient and procedural characteristics. 
Therefore, the Sponsor, Medical Expert, and coordinating investigator have determined that 
this clinical investigation is justified because its potential benefits outweigh potential risks. 
4.9. Study Rationale 
There is a wide variety of topical hemostatic devices, sealants and adhesives available on the 
market and these can generally be divided into products without active components, products 
that include active components that mimic natural coagulation and combined agents. 
Recently, there has been an increase in development of advanced hemostatic pads and 
patches that can provide hemostasis and sealant properties similar to fibrin sealants (e.g., 
TachoSil).6 GATT Technologies BV developed a hemostatic patch that consists of a gelatin 
carrier and synthetic activated polymers (NHS-POx). GATT-Patch has been developed to 
provide a fast and robust control of bleeding during surgery. 
In a pilot single-arm clinical trial of patients undergoing liver resection surgery in the 
Netherlands, the primary endpoint of successful hemostasis within 3 minutes was met with 
97.4% versus a literature-derived performance goal of 65.4% (P<0.001), with adequate safety 
of GATT-Patch confirmed. The current clinical investigation will be a pivotal randomized 
clinical trial that will evaluate the safety and efficacy of GATT-Patch versus TachoSil in 
elective open liver surgery.  
GATT-Patch is indicated for use as an adjunct to hemostasis in surgery for minimal, mild, or 
moderate bleeding sites when control of bleeding by standard surgical techniques (such as 
suture, ligature or cautery) is ineffective or impractical. GATT-Patch is intended to be used 
for management of hemorrhage during surgeries on the liver. 
The hemostatic GATT-Patch will be intended for use in adult patients. The safety and 
performance of the device has not been yet established for use in specific populations as 
children, pregnant or lactating women. 
It should not be used in patients with a known hypersensitivity to the component materials, 
including porcine proteins and brilliant blue (FD&C Blue #1). 
 
 
Page 26 of 94

5. STUDY OBJECTIVES AND ENDPOINTS 
5.1. Objectives and Hypotheses of the Clinical Investigation 
The objective of this clinical investigation is to compare the safety and efficacy of GATT 
Patch versus TachoSil in liver surgery. 
5.2. Study Endpoints 
5.2.1. Primary Efficacy Endpoint 
The primary efficacy endpoint of this study is defined as non-inferiority of GATT-Patch 
compared to TachoSil in the percentage of cases achieving hemostasis at 3 minutes without 
rebleeding at the 10-minute time point. Figure 2 below represents the sequence of events for 
hemostatic assessments and pre-specified time points for assessment. Hemostasis will be 
defined by a grade of 0 (None/Dry) on the Surface Bleeding Severity Scale (SBSS), of the 
direct surface onto which GATT-Patch or TachoSil is applied. The SBSS provides a 
clinically validated score for assessment of bleeding at the target site, and consists of 6 scales 
(0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe; not immediately life-threatening, 
5 = extreme; immediately life-threatening).7 Investigators will be trained and tested on the 
assessment scale prior to the clinical investigation to have consistent assessment of bleeding 
at the target site (Section 10.1).  
Figure 2. 
Sequence of Events for Enrollment, Hemostatic Assessments and Time 
Points.
 
Page 27 of 94

5.2.2. Secondary Endpoints 
5.2.2.1. 
Efficacy Endpoints 
The secondary endpoints for this clinical investigation as defined as: 
 
Median time to hemostasis in seconds (key secondary endpoint); 
 
Kaplan-Meier estimated distribution of time to hemostasis; 
 
Treatment failure, defined as no hemostasis at 10 minutes; 
 
Rebleeding after 10 minutes but before subject closure; and 
 
Percentage of hemostasis at 30, 60, 90, 120, 150, 240, 300, 360, 420, 480, 540 and 
600 seconds. 
Achievement of hemostasis will be verified every 30 seconds for the first 5 minutes and 
every 60 seconds between 5 and 10 minutes, starting from the time that the hemostatic patch 
is positioned and pressure is initiated. If hemostasis has not been achieved after 10 minutes of 
application (SBSS 1-5), then treatment is considered a failure and additional hemostatic 
agents or techniques may be used. If a subject is randomized to GATT Patch, rescue therapy 
cannot exist of products containing thrombin and/or fibrinogen. 
5.2.2.2. 
Safety Endpoints 
The safety of GATT-Patch will be assessed by the incidence, severity and relation to 
hemostatic device of all AEs. The AEs for the GATT-Patch group will be compared to those 
for the TachoSil group. 
All AEs will be collected, with adverse events of special interest being: 
 
Bleeding-related events, including rebleeding of the bleeding site(s) treated with 
hemostatic patch at any point in time (within 10 minutes of application, prior to 
subject closure, and postoperative), and including hematoma; 
 
Thromboembolic events;  
 
Biloma; and 
 
Allergic reaction. 
 
5.2.2.3. 
Exploratory Endpoints 
The exploratory endpoints for this clinical investigation are defined as follows: 
 
Procedure duration (minutes); 
 
Estimated blood loss (mL) during surgery; 
 
Number and type of blood transfusion during hospitalization; 
 
Duration of Intensive Care Unit (ICU) stay; 
 
Total hospitalization time; 
 
Postoperative drainage volume, characteristics, and duration; 
 
Need for and cause of reoperation; 
 
Imaging of the liver resection at 6 weeks post-surgery to detect (1) fluid collection 
and its size (in mL) and aspect, (2) pseudo-aneurysm, (3) patch encapsulation, and (4) 
rolling up of the device on the resection plane; 
 
Amount of hemostatic material needed versus bleeding surface; 
 
User satisfaction (questionnaire) for GATT-Patch (Appendix 1, Section 15.1.1);  
 
Physician treatment preference assessment (questionnaire) (Appendix 2, Section 
15.1.2); 
Page 28 of 94

 
Local recurrence of liver cancer at the resection; 
 
Cancer-free survival; and 
 
Overall survival. 
 
5.2.2.4. 
Five-year follow-up 
A full study report will be written based on the 3 month follow-up data and will be submitted 
to all relevant local country authorities, including a pre-market approval submission to FDA. 
Furthermore, 5 year observational follow-up will be performed to characterize long-term 
safety on all patients undergoing liver resection for liver malignancy or metastases, collecting 
data on local cancer recurrence, disease-free survival, and overall survival. This observational 
follow-up will not be in direct contact with patient, but through electronic health records 
have data up to 5-year follow-up collected. The 5 year observational review will be submitted 
to all relevant local country authorities through an annual progress report (i.e. FDA) or post-
market clinical follow-up report (i.e., countries with EU MDR regulations). 
Follow-up will be performed according to standard oncological follow-ups performed by the 
treating physician (e.g., oncologist or surgeon) and data will be collected at the following 
intervals: 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 30 months, 36 
months, 42 months, 48 months, 54 months and 60 months (see also Table 7). During each 
follow-up, data on results of tumor marker analyses (if applicable), performed imaging, 
diagnostic biopsy or surgical procedures, or other diagnostics will be collected. Furthermore, 
data on performed additional therapies for cancer during follow-up will be collected: (i) 
adjuvant systemic chemotherapy, immunotherapy, or other, (ii) locoregional therapy such as 
ablation, or (iii) (re-)resection of the liver cancer, primary cancer (if applicable), or 
metastases. 
 
 
Page 29 of 94

6. INVESTIGATIONAL PLAN 
 
6.1. Description of Overall Study Design and Plan 
This is a pre-market, prospective, randomized (2:1), multicenter, multi-national pivotal 
clinical investigation. 
Subjects meeting all eligibility criteria will be randomized (2:1) to receive the investigational 
device, GATT-Patch or the control, TachoSil, respectively. Patients will remain blinded for 
the randomized treatment and treatment given.  
Each surgery will be performed according to the standard procedures of the hospital, with the 
exception of the use of GATT-Patch versus TachoSil. Subjects who signed informed consent, 
who meet the preoperative eligibility criteria, and who have an appropriate bleeding site 
(SBSS 1, 2, or 3 [e.g., reflecting minimal, mild, or moderate bleeding severity] and no 
contraindications) will be randomized to receive GATT-Patch and TachoSil. Randomization 
will be performed intraoperatively after intraoperative eligibility criteria have been 
confirmed. Surgeons cannot be blinded on the hemostatic patch use. 
GATT-Patch will be used to control bleeding during open liver surgery. Each surgery will be 
performed according to the standard procedures of the hospital, with exception of the use of 
GATT-Patch or TachoSil. At the 6-week follow-up, imaging and some laboratory 
assessments may be considered study specific procedures, depending on standard-of-care 
follow-up assessments at sites. The study flow is shown below in Figure 3 and detailed 
further in the sections below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3. 
Study Design 
Page 30 of 94

 
*Including secondary endpoints during surgery 
6.2. Rationale for endpoint selection 
Endpoints were selected based on outcomes reported for other topical hemostatic agents in 
the scientific literature. A meta-analysis identified 15 articles reporting on hemostatic 
techniques during open liver surgery, and this included 6 articles that specifically reported on 
the percentage of hemostasis at 3 minutes.2,6,8,9,10,11,12 The percentage of hemostasis at 3 
minutes was found to be a clinically relevant performance outcome for success of various 
hemostatic techniques during open liver surgery. Data from six different randomized trials 
that evaluated hemostatic products during liver surgery were pooled to establish an expected 
rate of successful hemostasis at 3 minutes (Table 4). 
Table 4: Summary of Primary Endpoint Outcome reported in Scientific Literature and 
Used in Sample Size Calculation 
 
Reference 
Group 
N 
Time to hemostasis 
#a 
Hemostasis at 3 
min. 
Page 31 of 94

Bjelovic et al., 
2018 
Grifols 
52 
2.8 ± 0.1 min 
85.6% 
Surgicel 
49 
3.8 ± 2.4 min 
62.8% 
Bochicchio et al., 
2015 
Fibrocaps 
120 
1.0 (median) 
94.0% 
Gelfoam / Spongostan 
61 
2.0 min (median) 
70.0% 
Genyk et al., 2016 TachoSil 
114 
3.5 ± 1.3 min 
80.7% 
ORC (Surgicel) 
110 
5.5 ± 4.6 min 
50.0% 
Moench et al., 
2014 
TachoSil 
65 
3.38 ± 0.9 min 
80.0% 
Sangustop 
62 
2.2 ± 1.6 min 
86.9% 
Ollinger et al., 
2013 
Veriset 
32 
1.0 min (median) 
94.0% 
TachoSil 
18 
3.0 min (median) 
71.0% 
Verhof et al., 2015 Fibrocaps 
39 (NL) 
 47 (US) 
1.9 min 
76.9% (NL) 
 83.0% (US) 
Gelatin sponge (Gelfoam [US] or 
Spongostan [NL] 
17 (NL) 
 23 (US) 
4.8 min 
52.9% (NL) 
 34.8% (US) 
6 RCTs  
TachoSil, ORC (Surgicel), 
Sangustop, Veriset, Grifols, 
Fibrocaps, Gelatin sponge 
(Gelfoam or Spongostan) 
799 
Range 1 min - 5.5 
min 
Weighted average: 
 74.8% 
 (95% CI: 65.4% to 
83.1%) 
a # This is the mean time to hemostasis, if not otherwise reported. 
Page 32 of 94

The choice of TachoSil as the comparator has not been made to favor the test product, but to 
obtain the highest standards of clinical evidence in support of GATT-Patch by comparison 
with the standard-of-care hemostatic patch. Comparison with another hemostatic patch has 
the advantage of both products being ready-to-use, which limits blood loss during surgery 
and increases the comparability in safety and performance. The risk-benefit ratio for patches 
are similar because of comparable application methods and the position and structure of the 
patch on the target bleeding site in relation to the patient anatomy.  
By using TachoSil, a fibrin sealant patch, as the comparator, the standard of care hemostatic 
agent for open liver surgery, supported by the largest body of evidence from multiple 
randomized clinical trials (see Table 4), is used in this clinical trial. TachoSil has been used in 
n=197 patients versus only N=32 for Veriset. Moreover, TachoSil demonstrated to have the 
highest success rate in up to moderate bleedings, whereas non-active products (Surgicel, 
Gelfoam, Spongostan, ORC, and Sangustop) had lower rates of hemostasis. In addition, a 
network meta-analysis including 20 randomized trials, 3267 patients and 7 different 
interventions found that fibrin sealant patch and fibrin glue were the most effective 
interventions for achieving hemostasis during liver resection.1 Other hemostatic agents have 
been tested in the setting of open liver surgery with promising results, but the level of 
evidence is limited to only singular trials (i.e., Veriset). Moreover, other products are no 
longer available for clinical use (i.e., Fibrocaps). 
In the PMA submission of TachoSil for an indication as an adjunct to hemostasis during liver 
surgery, the pooled results of three randomized clinical trials reported that 174 of 233 
subjects (74.7%) in the TachoSil treatment group achieved hemostasis at 3 minutes compared 
with 117 of 231 subjects (50.6%) in the comparator treatment group (that was made up of 
non-actives) achieved this goal (P<0.0001). Nevertheless, because the rate of successful 
hemostasis at 3 minutes was 80.7% in the individual trial by Genyk et al10, GATT chooses to 
use an estimate of 80% in the power calculation for the current Pivotal clinical investigation.9 
6.3. Discussion of Study Design 
This is a prospective, randomized clinical trial. The study was designed in this fashion in 
order to assess a balanced subject population undergoing liver surgery and the comparative 
efficacy and safety of GATT-Patch to another widely used hemostatic patch. 
6.4. End of Study 
A subject will have fulfilled the requirements for study completion if/when the subject has 
completed all study periods, including Week 12 follow-up visit/assessment. A full study 
report will be written based on this 3 month follow-up data and will be submitted to all 
relevant local country authorities, including a pre-market approval submission to FDA. 
Furthermore, patients undergoing liver resection for liver malignancy or metastases will be 
observationally followed for 5 years to review local cancer recurrence, disease-free survival, 
and overall survival. This observational follow-up will not be in direct contact with the 
physician. The report will submitted to all relevant local country authorities through an 
annual progress report (e.g., for FDA) or post-market clinical follow-up report (e.g. for 
countries with EU MDR regulations).  
Page 33 of 94

Assessments (Table 7) OR as requested by Sponsor. 
 
 
Page 34 of 94

7. SELECTION OF STUDY POPULATION 
Section 12.2 provides information regarding number of subjects planned to be 
enrolled/randomized. 
7.1. Inclusion Criteria 
A subject must meet all of the following pre-operative inclusion criteria to be enrolled into 
the clinical investigation: 
1 Subject is scheduled to undergo elective open surgery on the liver; 
2 Subject is willing and able to give written informed consent for the clinical 
investigation participation; 
3 Subject is 22 years of age or older at the time of enrollment; and 
4 Subject has been informed of the nature of the clinical investigation. 
A subject must meet all of the following intraoperative inclusion criteria to be enrolled into 
the clinical investigation: 
1 Subject in whom the Investigator is able to identify a target bleeding site at the liver 
resection plane for which any applicable conventional means for hemostasis (e.g. 
suture, ligature or cautery) are ineffective or impractical, and the choice is made to 
use a hemostatic agent to stop the bleeding; and 
2 Subject has a target bleeding site with a SBSS of 1, 2, or 3 (e.g. reflecting minimal, 
mild or moderate bleeding severities). 
 
7.2. Exclusion Criteria 
A subject must not meet any of the following pre-operative exclusion criteria to be enrolled 
into the clinical investigation: 
1 The target bleeding site is from a large defect in an artery or vein that requires 
vascular reconstruction with maintenance of vessel patency; 
2 Subject is scheduled to undergo surgery on other organs than the liver and its 
associated biliary and vascular system; 
3 Subject is scheduled to undergo a staged liver surgery procedure (e.g., Associating 
Liver Partition and Portal vein ligation for Staged hepatectomy [ALPPS]); 
4 Subject is taking multiple antithrombotic therapies in therapeutic dosage up to the 
time of surgery, but allowing exclusive use of acetylsalicylic acid; 
5 Subject has platelet count <100 x 109/L, an activated partial thrombin time of >100s, 
or international normalized ratio >2.5; 
6 
 
7 Subject is pregnant, planning on becoming pregnant or actively breastfeeding during 
the 3-month follow-up period; 
8 Subject has a known hypersensitivity to brilliant blue (FD&C Blue #1), porcine 
gelatin, or horse proteins; 
9 Subject who has religious objections to receiving products with components of animal 
(porcine or equine) or human origin; 
10 Subject has an active or suspected infection at the bleeding site; 
11 Subject in whom the investigational device will be used at the site of a synthetic graft 
or patch implant;  
Page 35 of 94

12 Subject has a life expectancy of less than 3 months; 
13 Subject has a documented severe congenital or acquired immunodeficiency;  
14 Subject has had or has planned to receive any organ transplantation; 
15 Subject is currently participating or has participated in another clinical investigation 
within the past 30 days that may affect the endpoints of the study, such as trials 
related to the surgical procedure, and on anti-coagulation; 
16 Subject is not appropriate for inclusion in the clinical investigation, per the medical 
opinion of the Investigator; and 
17 Subject has any incidental (pre- and peri-operative) findings deemed by the 
Investigator to potentially jeopardize the safety or welfare of the subject. 
 
7.3. Rescreening 
Individuals who sign the informed consent form (ICF) to participate in the study but who do 
not subsequently meet all the requirements as outlined in the inclusion and exclusion criteria 
are considered screen failures. They will not be enrolled and may not be rescreened. 
7.4. Study Withdrawal, Removal, and Replacement of Subjects 
A sample size of 130 subjects of which a total of 87 subjects will undergo implantation of 
GATT Patch. 
The enrollment period is expected to take approximately 12 months, which includes an FDA 
review of data for the first 10 US subjects. The per subject duration of the clinical 
investigation from treatment to follow-up will be approximately 3 months. The total expected 
duration of the clinical investigation is, therefore, approximately 15 months. Furthermore, 5 
year observational follow-up will be performed to characterize long-term safety on all 
patients undergoing liver resection for liver malignancy or metastases, collecting data on 
local cancer recurrence, disease-free survival, and overall survival. This observational follow-
up will not be in direct contact with the patient, but through electronic health records and/or 
pre-operative and intra-operative inclusion criteria to be enrolled into the clinical 
investigation. It is expected that circa 80% of the subjects that pass pre-operative eligibility 
screening will pass intra-operative eligibility screening. 
A subject may withdraw or discontinue participation at any time during the clinical 
investigation. There is no need to provide a reason for withdrawal or discontinuation. The 
example due to non-compliance to the Clinical Investigation Plan (CIP) or if the investigator 
 
The Sponsor or its representative will be notified immediately when a subject is withdrawn or 
discontinued for any reason. Premature clinical investigation end date and reason (if known) 
will be documented on the electronic case report forms (eCRF). If a subject fails to return for 
a follow-up visit/assessment or cannot be contacted for a follow-up visit/assessment, the 
investigator will attempt to contact the subject to determine and document the reason for the 
subject failed to return and to encourage compliance with the study visit/assessment schedule. 
outside the study. 
Page 36 of 94

The data collected up to the time point the subject has withdrawn or discontinued will be 
included as part of the clinical investigation results. Additional safety information may be 
requested from a withdrawn or discontinued subject if it is considered clinically relevant. 
Subjects who withdrawn from the study will receive standard of care defined by applicable 
treatment Clinical Investigation Plan(s) for the disease at the investigational site. If any 
additional care is necessary because of the subjects' participation in the clinical investigation, 
this will be provided to the subject by the investigational site. 
There will be no replacement of subjects who have been treated with the investigational or 
control product. 
7.5. Investigational Sites 
This clinical investigation will be conducted in the US, Netherlands, and Germany. The 
clinical investigation in the US will be limited to 2 US sites; expansion to further sites in the 
US will be covered in an IDE supplement, which will be submitted to FDA after enrollment 
of 10 US subjects. The report will also be made available to other local country authorities 
for review upon request. Upon approval of the FDA, additional US sites will be included in 
the study. A maximum of 12 sites will participate in this clinical investigation, with a 
distribution as outlined in the table below (Table 5). 
Table 5. Number of Clinical Sites per Geography 
 
Minimum number of sites 
Maximum number of sites 
US 
4 
7 
Netherlands 
2 
4 
Germany 
2 
4 
Page 37 of 94

 
A single site may not enroll more than 20% of the total planned population, equivalent to no 
more than 26 subjects. Further, a minimum of 50% of the subjects will be enrolled in the 
United States to help ensure that the study subjects are representative of the US population 
for which this device will be indicated. 
7.6. Suspension or Premature Termination of the Clinical Investigation 
GATT Technologies BV reserves the right to terminate an investigator and/or investigational 
site for the following reasons:  
 
Failure to secure subject informed consent including protection of personal data prior 
to enrollment. 
 
Failure to report relevant safety events within 24 hours of discovery after learning of 
the event. 
 
Repeated investigational plan deviations. 
 
Repeated failure to appropriately complete case report forms. 
 
Failure to enroll an adequate number of subjects. 
 
Loss of or unaccounted for investigational product inventory. 
 In addition, GATT Technologies BV may choose to suspend or prematurely terminate the 
clinical investigation for the following reasons: 
 
Device deficiency or malfunction 
 
Production limitation 
 
Administrative decision 
GATT Technologies BV will promptly notify the investigators, ethics committees and 
regulatory authorities in this event and provide for appropriate therapy and follow-up for the 
subjects. 
 
In case of study termination or suspension, the investigators must inform the subjects 
and may inform the personal physician of the subjects to ensure appropriate care and 
follow-up is provided. In the case of a study suspension, subject enrollment must stop 
until the suspension is lifted. 
 
 
Page 38 of 94

 
8. TREATMENTS 
 
8.1. Details on the Investigational device 
GATT-Patch will be used to control bleeding during open liver surgery as per EU and US 
GATT-Patch IFU. The differences between IFUs in EU and US related only to the indication 
for use and do not impact safety and efficacy assessments of GATT-Patch or the conduct of 
the trial. Please refer to Section 4 of this CIP. 
8.1.1. Contraindications 
GATT-Patch is not indicated for use on severe (e.g., pulsatile) bleedings with a Surface 
Bleeding Severity Scale of 4 or 5. 
GATT-Patch is not intended for use on organs other than the liver. 
GATT-Patch is not intended for intravascular use. Do not attempt to force GATT-Patch into 
blood vessels, and only apply GATT-Patch after standard surgical techniques have been used 
to close the vessel. 
GATT-Patch should not be used in infected wounds. 
GATT-Patch should not be used in patients with a known hypersensitivity to the component 
materials, including porcine proteins and FD&C Blue #1. 
8.1.2. Warnings 
GATT-Patch has not been studies in pregnant or lactating women. 
GATT-Patch is not intended to be a substitute for standard surgical technique and/or the 
proper use of other conventional hemostatic techniques. 
GATT-Patch should not be used when applying pressure on the entire surface of the patch 
would be difficult to achieve. 
Care should be taken when using GATT-Patch in confined spaces. 
Use the smallest number of patches required to cover and extend the margins of the entire 
bleeding area by at least 1 cm. Maximum dosage for GATT-Patch is 150 cm2, calculating to 
approximately 3 GATT-Patches, based on a 70 kg patient or 2.1 cm2 / kg. The safety of 
higher dosages has not been studied. 
GATT-Patch should not be hydrated prior to application. 
Do not replace, reposition, or peel off GATT-Patch after application with a wet gauze. 
GATT-Patch should be wetted homogenously after application. 
Degradation of GATT-Patch depends upon several factors including the amount used, degree 
of saturation with blood or other fluids (e.g., bile) and the tissue bed. 
Contact with bile may impact the performance of GATT-Patch. 
Prior to resorption, GATT-Patch may be present on imaging. 
Page 39 of 94

After application of GATT-Patch, manipulation of the bleeding site and the patch should be 
minimized. 
Due to the properties of the product, it is expected that it can be combined with drugs. For 
information, please read the package insert of the respective medication. 
8.1.3. Precautions 
For single use only. Do not re-sterilize. Reuse of single-use devices creates a potential risk of 
patient infections. 
Discard if packaging is damaged. 
GATT-Patch should be used within 1 hour after the opening. 
8.1.4. Administration 
GATT-Patch is intended to be used by physicians trained in performing specific open 
surgical procedures when adequate pressure can be achieved upon application. 
Dry gloves and surgical instruments (forceps, scissors) should be used to handle, cut and 
apply GATT-Patch. When applying GATT-Patch, minimize contact with wet or bloody 
surgical instruments or gloves as the adhesive may adhere to other surfaces. 
GATT-Patch should not be hydrated prior to placement. 
GATT-Patch may be cut to the desired size and shape. Select the appropriate size of GATT-
Patch so that it overlaps the margins of the bleeding surface by at least 1 cm. 
Multiple patches may be used for larger bleeding surfaces. GATT-Patch may be applied to, or 
 
It is recommended that dry parts of GATT-Patch after application are wetted. 
Leave GATT-Patch in situ after hemostasis has been achieved. Do not try to forcefully 
remove the patch. 
Do not remove GATT-Patch at the end of the surgery. Excess GATT-Patch material may be 
removed carefully, at the discretion of the surgeon. 
Surgeons may use up to three patches, or multiple (cut) parts of patches, as long as total 
material used is no more than three full patches in total in the subject. Patch may be applied 
-on-
 
If hemostasis has not been achieved after using three patches, other hemostatic 
agents/techniques may be used. If a subject is randomized to GATT-Patch, rescue therapy 
cannot exist of products containing thrombin and/or fibrinogen. 
The following method of application is provided in the EU and US IFU of GATT-Patch: 
 
Apply GATT-Patch dry to the bleeding site with at least 1 cm margins and hold in 
place with a saline wetted gauze and uniform pressure over the entire patch surface 
for 30 seconds. Gently remove the wet gauze from the patch. If complete hemostasis 
has not been achieved in 30 seconds, re-apply pressure with a saline wetted gauze or 
surgical sponge for an additional 30 seconds; 
Page 40 of 94

o If hemostasis is not complete with a single patch and blood comes through the 
patch, apply a new (piece of) GATT-Patch on the bleeding site with a 1 cm 
overlap with tissue or previously placed GATT-Patch on all sides ("patch-on-
patch"). Apply according to the steps above. 
o If hemostasis is not complete because GATT-Patch is not adherent to the 
underlying tissue, with or without hematoma formation underneath, remove 
the non-adherent part and apply a new (piece of) GATT-Patch on the bleeding 
site with a 1 cm overlap with tissue or previously placed GATT-Patch on all 
sides ("patch-on-patch"). Apply according to the steps above. 
o Repeat the above steps as necessary, with a maximum of 2.1 cm2/kg of 
subject body weight covered by GATT-Patch and remaining in-situ at the end 
of the operation (approximately 3 patches in an adult patient of 70 kg). 
 
8.1.5. Handling in the Clinical Trial 
To ensure adequate endpoint assessment in this clinical investigation, no manipulation of 
GATT-Patch and the Target Bleeding Site should be performed up to 10 minutes after 
GATT-Patch application, unless extra pressure or an additional patch is required per EU and 
US IFU and scenarios below. 
As described in the EU and US IFU, certain situations can occur in which hemostasis is not 
achieved after an initial 30 seconds application time. The following description, and Figure 4, 
provides more details: 
 Hemostasis is achieved (SBSS 0) but blood builds up underneath GATT-Patch as shown 
by a dome formation (e.g., caused by inadequate pressure) 
 re-apply 30 seconds of 
pressure. If after an additional 30 seconds of pressure a dome again arises, cut away the 
dome and apply a new (piece of) GATT-Patch on the bleeding site with a 1cm overlap 
with tissue or previously placed GATT-Patch on all sides. Apply pressure for 30 seconds. 
Repeat as necessary for up to 10 minutes. If hemostasis is achieved (SBSS 0) and GATT-
Patch is adhesive to the tissue 
 leave GATT-Patch in place and do not manipulate until 
10 minutes from the initial application have passed. 
 
-Patch is not adherent to underlying 
tissue (e.g., caused by inadequate pressure) 
 re-apply 30 seconds of pressure. If after an 
additional 30 seconds of pressure (a part of) GATT-Patch is not adherent, cut away the 
non-adherent part and apply a new (piece of) GATT-Patch on the bleeding site with a 1 
cm overlap with tissue or previously placed GATT-Patch on all sides. Apply pressure for 
30 seconds. Repeat as necessary for up to 10 minutes. If hemostasis is achieved (SBSS 0) 
and GATT-Patch is adhesive to the tissue 
leave GATT-Patch in place and do not 
manipulate until 10 minutes from the initial application have passed. 
 Hemostasis is not achieved as blood is coming through GATT-
 re-
apply 30 seconds of pressure. If after an additional 30 seconds of pressure, blood is still 
coming through the patch (e.g., potential cause is puncture of the patch), apply an 
additional (piece of) GATT-
-on-
cm overlap on the previously placed GATT-Patch on all sides. Apply pressure for 30 
seconds. Repeat as necessary for up to 10 minutes. If hemostasis is achieved (SBSS 0) 
and GATT-Patch is adhesive to the tissue 
 leave GATT-Patch in place and do not 
manipulate until 10 minutes from the initial application have passed. 
Page 41 of 94

Figure 4. 
GATT Application Flowchart 
 
8.2. Details on the control product 
The control device for this study is TACHOSIL® Fibrin Sealant Patch (Baxter Healthcare 
Corporation; Deerfield, IL, USA; hereinafter referred to as TachoSil). TachoSil is a fibrin 
sealant patch indicated for use with manual compression in adult and pediatric patients as an 
adjunct to hemostasis in cardiovascular and hepatic surgery, when control of bleeding by 
standard surgical techniques (such as suture, ligature or cautery) is ineffective or impractical. 
TachoSil is a topical fibrin sealant patch consisting of human fibrinogen and human thrombin 
coated onto an equine collagen sponge. TachoSil usage in this clinical investigation will be in 
application of 3 minutes. 
TachoSil was selected as the control device for this clinical investigation for the following 
reasons: 
 
One of the most commonly used hemostatic patchesb, c 
 
Indication includes hepatic surgery 
 
Is also a patch and therefore has similarity in application method and presents similar 
risks 
 
Is a ready-to-use product allowing direct comparison without preparation time variation 
 
Is considered to be the standard-of-care hemostatic patch because of its high hemostatic 
performance of ~80% hemostasis at 3 minutes, as compared with ~60% with non-active 
products 
 
b https://ec.europa.eu/commission/presscorner/detail/en%3E/ip_20_529 
c https://ec.europa.eu/competition/mergers/cases1/202046/m9547_780_6.pdf 
Page 42 of 94

8.3. Surgical procedure 
Each surgery will be performed according to the standard procedures at the hospital, with 
exception of the randomized use of GATT-Patch or TachoSil. GATT-Patch or TachoSil will 
be used if the subject has an appropriate bleeding site (SBSS 1, 2 or 3 as shown in Table 6 
below).7 Randomization to the use of GATT-Patch or TachoSil will only be considered during 
and/or after resection when control of bleeding by standard surgical techniques (such as suture, 
ligature or cautery) is ineffective or impractical, and the surgeon has made the decision to apply 
a topical hemostatic product. If there are multiple appropriate (SBSS 1-3) bleeding sites that 
require use of a topical hemostatic product, the first encountered bleeding site that requires 
topical hemostat application will be considered for the primary endpoint, but information on 
achieved hemostasis will also be collected for additional bleeding sites. 
Table 6. Surface Bleeding Severity Scale  
SBSS Score 
0 
1 
2 
3 
4 
5 
Verbal 
Descriptor 
None 
Minimal 
Mild 
Moderate 
Severe; not 
immediately 
life-
threatening 
Extreme; 
immediately 
life-
threatening 
Visual 
Descriptor 
Dry 
Oozing 
Pooling 
Flowing 
Streaming 
Gushing 
Expected 
Intervention(s) 
None 
Manual 
pressure, 
cautery, 
adjuvant 
hemostat(s) 
Manual 
pressure, 
cautery, 
suture, 
adjuvant 
hemostat(s) 
Manual 
pressure, 
cautery, 
suture, 
adjuvant 
hemostat(s) 
Manual 
pressure, 
cautery, 
suture, 
staples, 
tissue repair 
Manual 
pressure, 
cautery, 
suture, 
staples, 
tissue repair 
Maximum 
Expected 
ACS-ATLS 
Shock Risk 
Class 
1 
1 
1 
2 
3 
4 
ACS-ATLS Shock Risk: American College of Surgeons - Advanced Trauma Life Support 
Class1: involves up to 15% of blood volume; typically, no change in vital signs and fluid 
resuscitation is not usually necessary. 
Class 2: involves 15%-30% of total blood volume; subject is often tachycardic with a narrowing 
of the difference between the systolic and diastolic blood pressures; the body attempts to 
compensate with peripheral vasoconstriction; skin may start to look pale and be cool to the touch; 
volume resuscitation with crystalloids is all that is typically required; blood transfusion is not 
typically required. 
Class 3: involves loss of 30%-
heart rate increases, peripheral hypoperfusion worsens; fluid resuscitation with crystalloid and 
blood transfusion are usually necessary. 
is reached, and aggressive resuscitation is required to prevent death. 
 
Once intraoperative eligibility criteria are met, then the subject is formally randomized and 
enrolled into the clinical investigation. Randomization will be performed through Interactive 
Voice/Web Response System. Randomization to GATT-Patch and TachoSil will occur in a 2:1 
ratio and stratified by site using random permuted block sizes of three or six for treatment 
assignment. 
Page 43 of 94

The handling instructions for GATT-Patch are provided in specific EU and US instructions for 
use (IFU) of the device. Select the appropriate size of the patch so that it overlaps the margins 
of the bleeding surface by at least 1 cm. The patch may be cut to the desired size and shape. 
Dry gloves and surgical instruments (forceps, scissors) should be used to handle and cut GATT-
Patch. GATT-Patch can be placed on a wet gauze prior to placement, and after excess blood is 
removed from the bleeding site, directly applied on the bleeding site with continuous pressure 
for an initial 30-seconds application time. Application of TachoSil will follow the 
-minute application time. The primary endpoint of this 
investigation is hemostasis at 3 minutes, and therefore, is in line with the TachoSil IFU. 
The choice for a different application time for GATT-Patch and TachoSil is supported by the 
specific design of GATT-Patch to achieve hemostasis quickly, as shown by the 82% rate of 
hemostasis after 30 seconds with GATT-Patch in the first-in-human trial (see Section 4.7). 
Therefore, the shorter compression times and assessment of hemostasis prior to the 3 minute 
time point for GATT-Patch is not anticipated to pose additional safety concerns for the patient. 
A shorter application time of TachoSil to align with GATT-Patch is inappropriate as it is 
assumed that the hemostatic performance of TachoSil will be less than the anticipated 75-80% 
at 3 minutes if handled under less optimal conditions than outlined in the IFU. 
For calculation of the median time to hemostasis, achievement of hemostasis will be verified 
every 30 seconds starting after the initial 30 seconds of application for GATT-Patch, and every 
30 seconds after the initial 3 minutes for TachoSil up to the 5-minute time point, and every 60 
seconds between 5 and 10 minutes. 
The primary performance endpoint is defined by the percentage of cases achieving 
hemostasis at 3 minutes without rebleeding within 10 minutes. Hemostasis will be defined by 
a grade of 0 (None/Dry) on the SBSSd.
If hemostasis has not been achieved after 10 minutes of application (SBSS 1-5), then 
treatment is considered a failure and other additional hemostatic agents/techniques may be 
used. Subjects randomized to GATT-Patch may not undergo rescue with TachoSil and those 
subjects randomized to TachoSil may not undergo rescue with GATT-Patch. In the case 3 full 
GATT-Patches have been applied and a bleeding site other than a previously treated target 
bleeding site is identified, other additional hemostatic agents/techniques may be used that do 
not contain fibrinogen and/or thrombin components. 
Placement of surgical drains will be left at the discretion of the treating surgeon on whether it 
is clinically indicated. 
The investigators will complete a user questionnaire at the end of each procedure. At the end 
of the trial, each investigator will be asked to complete a physician preference questionnaire 
on GATT-Patch versus TachoSil. 
The following procedural data will be collected: 
 
Surgical procedure data: 
 
d The Surface Bleeding Severity Scale (SBSS) provides a validated score for assessment of bleeding at the target 
site, and consists of 6 scales (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe; not immediately life-
threatening, 5=extreme; immediately life threatening) (Spotnitz, 2017). Investigators will be trained and tested 
on the assessment scale prior to the clinical investigation to have consistent assessment of bleeding at the target 
site. 
Page 44 of 94

o Date of surgery 
o Description of surgical procedure of the liver (e.g., anatomic or non-anatomic 
resection and extent of resection (e.g., left hemihepatectomy, right 
hemihepatectomy, 
extended 
left 
hemihepatectomy, 
extended 
right 
hemihepatectomy, segmentectomy [and which segment], bisegmentectomy 
[and which segments], trisegmentectomy [and which segments], non-
anatomical wedge resection(s) and its location(s)) 
o Vascular reconstruction performed (yes/no) 
o Biliary tree reconstruction performed (yes/no) 
o Type of hepatic parenchyma (e.g., normal, cirrhotic, staetotic) 
o Maneuvers to limit liver blood inflow (e.g., none, Pringle, total vascular 
exclusion, other) and duration 
o Resection method (e.g., Cavitron Ultrasonic Surgical Aspirator [CUSA], 
harmonic scalpel, scalpel, other) 
o Estimated size (cm x cm) of resection area(s) 
o Description of target bleeding site(s) (location) 
o Estimated size (cm x cm) of target bleeding site(s) 
o Number and size (cm x cm) of devices used 
o Amount of hemostatic material needed versus bleeding surface; 
o Use of conventional means for hemostasis before topical hemostat use (e.g., 
cautery, sutures or staples) 
o SBSS (0-5) of target bleeding site(s) at each pre-specified time point 
o Time of SBSS classification 
o Randomization to GATT-Patch or TachoSil 
o Time of randomization 
o Use of any (and which) rescue treatments after ineffective randomized treatment 
with GATT-Patch or TachoSil 
o Number and type of intraoperative blood transfusions 
o Incidence of any device deficiencies 
o Incidence of any complications or AEs 
o Estimated blood loss (mL) 
o Procedure duration (from start incision to surgical site closure) 
o Use of surgical drains 
o User satisfaction per investigator per procedure (questionnaire) 
o Macroscopic R0 resection for patients undergoing surgery for malignancy 
o Microscopic R0/R1 resection for patients undergoing surgery for malignancy 
 
Hospitalization: 
o 
 
o Total hospitalization period 
o Postoperative drainage volume, characteristics, and duration; 
o Analysis of drainage fluid for bilirubin, if applicable; 
o Number and type of blood transfusions during post-operative hospitalization 
o Need for and cause of reoperation at the target bleeding site; 
o Incidence of any complications or AEs; and  
o Laboratory test data. 
Page 45 of 94

 
8.4. Measures to Minimize Bias 
Due to the physical differences in the investigational and control devices, blinding of the 
surgeon is not possible. However, bias is minimized during this clinical investigation by 
performing a randomized trial and conducting this under the terms of an approved clinical 
investigation plan, use of specific inclusion and exclusion criteria, careful definitions for 
clinical investigation procedures and outcomes, and prospectively defined methods of data 
analysis.  Moreover, a validated bleeding scale is used to assess the severity of bleeding before 
randomization and to evaluate hemostasis after patch use. The baseline bleeding severity will 
be assessed prior to randomization, at which point in time the investigator is not aware of the 
treatment assignment. Further, the training and testing required for all investigators to use a 
validated bleeding severity scale for the assessment of successful hemostasis reduces 
subjectivity for the efficacy assessments. 
For the evaluation of safety events, bias is reduced by: 
 Blinding patients to the randomized and received treatment;  
 An independent adjudication committee will review all serious adverse events (SAEs) 
and adverse events of special interest (e.g., bleeding-related events, thromboembolic  
events, biloma, and allergic reaction) occurring during the 3-month follow-up after 
surgery for relatedness to the device and expectedness of the event based on the clinical 
scenario comprising of patient and procedural characteristics;  
 A blinded independent data monitoring committee will review the overall safety and 
efficacy of the trial. 
 
8.5. Device Accountability and Compliance 
The principal investigator (PI) or other designated individual will maintain records of device 
delivered to the study site, the inventory at the study site, the distribution to and use by each 
subject, and the return of materials to the Sponsor for storage or disposal. These records should 
include dates, quantities, batch/serial numbers, expiration dates, and unique code numbers 
assigned to the device and study subject. 
Administration of study device will be supervised by study site personnel to ensure compliance. 
8.5.1. Device Accountability 
Access to investigational devices will be controlled and the investigational devices will be used 
only in the clinical investigation and according to the CIP. 
The Sponsor will keep records to document the location of all investigational devices from 
shipment of investigational devices to the investigational sites until return or disposal. 
Investigational devices can be traced by a unique LOT number. The devices will be labelled 
 
Page 46 of 94

The Sponsor will have instructions in place and make packaging materials available, if 
applicable, for the safe return or disposal of investigational devices, including potentially 
hazardous devices. 
The PI or an authorized designee will keep records documenting the receipt, use, return and 
disposal of the investigational devices, which will include: 
 name(s) of person(s) who received, used, returned or disposed the device, 
 the date of the receipt, 
 identification of each investigational device (batch number/serial number or unique 
code), 
 quantity of investigational devices, 
 the expiry date, if applicable, 
 the date or dates of use, 
 subject identification, 
 the date of return of unused, expired or malfunctioning investigational devices, if 
applicable, 
 the date and documentation of disposal of the investigational devices as per instructions 
of the Sponsor, if applicable. 
Written procedures will be established for the entire process of device accountability. 
8.6. Prior and Concomitant Therapy/Medication 
Restricted prior therapies are provided in Section 7.2. 
Medications taken by or administered to the subject at the time of screening will be recorded 
in the eCRF. After the baseline visit, any concomitant medication is acceptable. Medication or 
therapy that is taken by or administered to the subject during the course of the study must be 
recorded in the eCRF. Anesthetics used for the surgery are not required to be entered as 
concomitant medication. The entry must include the dose, regimen, route, indication, and dates 
of use. 
 
 
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9. STUDY PROCEDURES
Table 7 outlines the timing of procedures and assessments to be performed throughout the 
study. Section 11.3 specifies laboratory assessment samples to be obtained. See Sections 5 and 
11 for additional details regarding efficacy assessments and safety assessments, respectively.
Table 7. Schedule of assessments
*In situations where the patient is screened during the admission before surgery, this is considered to 
be the screening visit and no additional visit at admission before surgery is performed.
**At least once before surgery during one of the assessments, with the latest data being the final pre-
surgical data used in analyses.
*** Ultrasound imaging is mandatory at the Week 6 (±2 weeks) follow-up point. If other imaging, for 
example Computed Tomography (CT), is performed in this follow-up window per standard of care for 
the evaluation of adverse events, these can replace the requirements of ultrasound imaging.
**** The last assessment with direct patient contact is at week 12 ± 2 regardless of indication for 
surgery. Patients undergoing liver resection for liver malignancy or metastases will be observationally 
followed for 5 years to review local cancer recurrence, disease-free survival, and overall survival. This 
observational follow-up will not be in direct contact with the patient, but through electronic health 
A full study report will be written based on the 3 month follow-up data and will be submitted 
to all relevant local country authorities, including a pre-market approval submission to FDA. 
Page 48 of 94

Furthermore, patients undergoing liver resection for liver malignancy or metastases, will be 
observationally followed for 5 years to review local cancer recurrence, disease-free survival, 
and overall survival, and submitted to all relevant local country authorities through an annual 
progress report (e.g., for FDA) or post-market clinical follow-up report (e.g., for countries 
with EU MDR regulations). 
9.1. Informed Consent 
Prior to performing any study-specific procedures, a detailed explanation of the study 
procedures, potential discomforts, risks and benefits of participation, and alternatives will be 
reviewed with potential study subjects by a qualified and delegated member of the 
investigational site study team. Subjects will be provided adequate time to review the 
informed consent document and all questions will be answered to the satisfaction of the 
subject prior to signing the informed consent. 
If the subject is willing to participate in the clinical investigation, he/she or an authorized 
legal representative must signed the ICF indicating that they have read and understand the 
information provided. Each investigational site will follow their local independent ethics 
committee (IEC)/institutional review board (IRB) and applicable regulatory guidelines for 
obtaining informed consent. Documentation of the informed consent process for each subject 
and the original signed consent will be retained at the investigational site. 
9.2. Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 7). Section 11.3 specifies laboratory assessment samples to be obtained. 
Assessments and procedures scheduled at a visit where study device is administered should 
be performed before treatment unless otherwise indicated in the Schedule of Assessments 
(Table 7). The expectation is that all assessments scheduled for this study are similar to a 
-Patch, and week 6 follow-up 
imaging and additional laboratory assessments (which will differ between countries and 
sites).  
Efficacy assessments are described in Section 5. 
Safety assessments are described in Section 11. 
The investigator may, at his/her discretion, arrange for a subject to have a medical assessment 
outside the study specified visits (Week 6 and Week 12), especially in the case of AEs that 
require follow-up, rehospitalization, or are considered by the investigator to be possibly 
related to the use of investigational device. The additional visit/assessment eCRF page must 
be completed for these medical assessments/visits. Follow-up of AEs, adverse device effects 
(ADEs), serious adverse events (SAEs), serious adverse device effects (SADEs), and 
unanticipated serious adverse device effect (USADEs) leading to study discontinuation is 
required (as further specified in Section 11.5Adverse Events). 
10. CLINICAL PERFORMANCE ASSESSMENTS 
The Schedule of Assessments (Table 7) outlines the efficacy assessments to be performed 
throughout the study and their timing. 
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On-site initiation visits will be organized, in which full training will be given to all 
appropriate staff members participating in the clinical investigation, including (principal) 
investigators, study coordinators and any other site personnel pivotal to the conduct of the 
clinical investigation. This training will include: instructions on the functions and use of the 
investigational device by the Sponsor, IFU on the control product, training on SBSS for 
assessment of bleeding at the target site, procedures outlined in the CIP, main principles of 
Good Clinical Practices for Medical Devices (ISO 14155), instructions on completion of the 
eCRFs, content of the investigator site file, and management of device deficiencies. 
 
10.1. 
Surface Bleeding Severity Scale (SBSS) 
The investigators at each site will have training on the SBSS prior to the enrollment of any 
subjects. Training will be in conformity with GATT Technologies procedure as described in 
internal GATT document DHF-01-SR-107 (Appendix 3). In summary, investigators will be 
taught on the severity of bleeding via 36 instructional videos of different scenarios of blood 
flow and bleeding area size. Subsequently, investigators will undergo a test in which they are 
shown 108 videos in a random order, for which they have to indicate the bleeding severity on 
a scale of 0-5 on the SBSS. Training on the SBSS will be performed to reduce intra-rater 
variability in the assessment of bleeding at the target site, and adequate evaluation of 
hemostasis after application of the investigational or control product. A certificate will be 
provided when successfully completing the test and is subsequently filed in the Trial Master 
File (TMF). Only those surgeons trained and tested on the SBSS will be permitted to assess 
bleeding severity and hemostatic performance. 
Clinical performance of GATT-Patch will be assessed using the SBSS. Hemostasis will be 
assessed at the pre-defined time points and is defined as an SBSS of 0 (none/dry). As this 
endpoint is assessed intraoperatively, study staff will undergo training on study-specific 
assessments and documentation processes. 
10.2. 
Investigational Device and Procedure 
All investigators will have training on the investigational device prior to the start to reduce a 
potential influence of a learning curve in using the device on outcome. A training record on 
the investigational device training will be signed on completion of the training and filed in 
the TMF. The PI will get acquainted with use of the device during implantation in animals, 
after which they can use GATT-Patch on trial subjects. Each additional surgeon that has not 
yet used GATT-Patch will be proctored by the PI or an experienced investigator that has 
previously used GATT-Patch at least once. The flow of training by proctoring is further 
explained in Figure 5. A training record for the proctoring session will be signed on 
completion of the training and filed in the TMF. 
Page 50 of 94

Figure 5. 
GATT-Patch Training Flow Chart 
 
PI = principal investigator; numbers reflect additional surgeons performing surgery with GATT-Patch 
 
 
Page 51 of 94

11. SAFETY ASSESSMENTS 
Safety assessments (vital signs, AEs, ADEs, SAEs, SADEs, clinical laboratory results 
(routine hematology and biochemistry) are to be performed at Clinical Investigation Plan-
specified visits, as specified in the Schedule of Assessments (Table 7). 
11.1. 
Medical History 
Medical history will be recorded at screening. Investigators should document the occurrence, 
signs, an
illnesses, up to screening. Additional preexisting conditions present at the time when 
informed consent is given and up to the time of treatment are to be regarded as concomitant. 
Medical history will include the following: 
 Allergies 
 Smoking history (and current) 
 Cardiac disorder(s) 
 Systemic hypertension 
 Renal dysfunction 
 Diabetes 
 Hereditary blood disorder(s) 
 Blood transfusions in the last 3 months 
 Previous abdominal surgery 
 Liver disease 
o Child-Pugh classification 
 Portal hypertension 
 Malignancies and prior therapies 
 Indication for surgery (e.g., hepatocellular carcinoma, colorectal metastases, non-
colorectal metastases, cholangiocarcinoma, benign tumor, other) 
 Other critical medical condition or previous surgery 
 ASA classification 
Illnesses first occurring or detected during the study and/or worsening of a concomitant 
illness during the study are to be documented as AEs on the eCRF in accordance with Section 
11.5. All changes not present at baseline or described in the past medical history and 
identified as clinically noteworthy must be recorded as AEs. 
Additionally, demographic data will be collected for all subjects and include: 
 Age 
 Sex 
 Race and ethnicity 
Race and ethnicity data is being collected for two primary reasons: 
 The incidence of hepatic disease differs between racial backgrounds; and 
 
and Ethnicity Data in Clinical Trials
 
 
11.2. 
Physical Examination 
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A physical examination (to include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, and neurological systems) will be performed at time points 
according to Schedule of assessments (Table 7). Care should be taken to examine and assess 
at the screening visit or at admission before surgery. 
Vital signs (heart rate, and systolic and diastolic blood pressure measurements, oxygen 
saturation) will be evaluated at the visits indicated in the Schedule of Assessments (Table 7). 
Blood pressure measurements are to be taken in the same arm for the duration of the study. 
Body weight (without shoes) will be recorded before surgery during the screening or 
admission assessment and after surgery when clinically indicated; height (without shoes) will 
be recorded at screening only. 
Vital sign measurements will be repeated if clinically significant or machine/equipment 
errors occur. Out-of-range blood pressure, oxygen saturation or heart rate measurements will 
vital sign measurements must be recorded as AEs. 
11.3. 
Laboratory Assessments 
Laboratory tests will be collected prior to surgery, and through the postsurgical admission. 
are required per this CIP. Test
results will only be captured if these test data is collected per standard of care. 
Table 8. Laboratory Testing Schedule 
Laboratory Tests 
Screening 
Admission Before 
Surgery* 
Through 
Admission** 
Week 6 (±2 
Weeks) 
Hematology 
 
 
 
 
Complete blood count 
X 
* 
X 
X 
Coagulation 
 
 
 
 
Prothrombin time (PT) 
X 
* 
X 
** 
Activated partial 
thromboplastin time (aPTT) 
X 
* 
X 
** 
International Normalized 
Ratio (INR) 
X 
* 
X 
** 
Chemistry 
 
 
 
 
Bilirubin 
X 
* 
X*** 
X 
Calcium 
X 
* 
** 
** 
Potassium 
X 
* 
** 
** 
Sodium 
X 
* 
** 
** 
Chloride 
X 
* 
** 
** 
Albumin 
X 
* 
X 
X 
Creatinine 
X 
* 
X 
** 
Asparate transaminase (AST) 
X 
* 
X 
X 
Alanine transaminase (ALT) 
X 
* 
X 
X 
Gamma Glutamyl 
Transferase (gGT) 
X 
* 
X 
X 
Page 53 of 94

Laboratory Tests 
Screening 
Admission Before 
Surgery* 
Through 
Admission** 
Week 6 (±2 
Weeks) 
Other 
 
 
 
 
Pregnancy test (if applicable) 
X 
* 
N/A 
N/A 
*Should be performed at least once before surgery during the screening visit or admission before surgery 
assessments, with the latest data being the final pre-surgical data used in analyses. 
**Timing of collection of this data will be according to standard of care hospital procedures. 
***And of the drainage fluid of a surgical drain, if applicable. 
Page 54 of 94

11.4. 
Equipment for Assessment  
The following equipment will be required for assessment of endpoints: 
 Imaging system for ultrasound of liver resection area, or other imaging modalities are 
allowed if performed per standard of care or evaluation of potential AEs; and 
 Stopwatch. 
Blood samples will be analyzed at local laboratories at each site. All laboratory reports must 
be reviewed, signed, and dated by the investigator. A legible copy of all reports must be filed 
laboratory test result considered by the investigator to be clinically significant should be 
considered an AE (clinically significant AEs include those that require an intervention). 
Clinically significant abnormal values occurring during the study will be followed up until 
repeat test results return to normal, stabilize, or are no longer clinically significant. 
11.5. 
Adverse Events 
11.5.1. Adverse Events 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device and whether anticipated or 
unanticipated. 
This definition includes events related to the investigational medical device; events related to 
the procedures involved.  
Subjects will be instructed to report AEs at each study visit. All AEs are to be followed up 
until resolution or a stable clinical endpoint is reached. 
Each AE is to be documented on the eCRF with reference to date of onset, duration, 
frequency, severity, relationship to investigational device, action taken with study device, 
treatment of event, and outcome. Furthermore, each AE is to be classified as being serious or 
nonserious. Changes in AEs and resolution dates are to be documented on the eCRF. 
For the purposes of this study, the period of observation for collection of AEs extends from 
the time the subject is enrolled and randomized until the last follow-up visit at 3 months. 
Follow-up of the AE is required if the AE persists until the event resolves or stabilizes at a 
level acceptable to the investigator. 
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the event should be noted. If the severity category changes over a number of 
days, then those changes should be recorded separately (with distinct onset dates). 
The severity of AEs will be graded according to the ISO14155:2020. 
Specific guidelines for classifying AEs by severity and relationship to investigational device 
are given in Table 9 and Table 10. 
 
 
Table 9. Classification of Adverse Events by Severity 
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MILD: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing no loss of 
time from normal activities. Symptoms do not require therapy or a medical evaluation; signs and symptoms 
are transient. 
MODERATE: Events introduce a low level of inconvenience or concern to the participant and may interfere 
with daily activities but are usually improved by simple therapeutic measures; moderate experiences may 
cause some interference with functioning. 
SEVERE: 
therapy or other treatment; they are usually incapacitating. 
 
Table 10. Classification of Adverse Events by Relationship to Study Device 
NOT RELATED: The relationship to the device, comparator or procedures can be excluded when: 
- 
the event has no temporal relationship with the use of the investigational device or the procedures to 
application of the investigation device. 
- 
the serious adverse event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible. 
- 
the discontinuation of medical device application or the reduction of the level of activation/exposure 
- when clinically feasible - and reintroduction of its use (or increase of the level of 
activation/exposure), do not impact on the serious adverse event. 
- 
the event involves a body-site or an organ that cannot be affected; the serious adverse event can be 
attributed to another cause (e.g., an underlying or concurrent illness/ clinical condition, an effect of 
another device, drug, treatment or other risk factors). 
- 
the event does not depend on a false result given by the investigational device used for diagnosise, 
when applicable. 
- 
harms to the subject are not clearly due to use error. 
- 
the event depends on a false result given by the investigational device used for diagnosisf, when 
applicable. 
In order to establish the relatedness, not all the criteria listed above might be met at the same time, depending 
on the type of device/procedures and the serious event. 
POSSIBLE: The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, is weak but cannot be ruled out completely. Alternative causes are also possible (e.g., an 
underlying or concurrent illness/ clinical condition or/and an effect of another device, drug or treatment). 
Cases where relatedness cannot be assessed or no information has been obtained should also be classified as 
possible.  
PROBABLE: The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, seems relevant and/or the event cannot reasonably be explained by another cause, 
 
e If an investigational device gives an incorrect diagnosis, the subject might, for example, receive an unnecessary treatment and incur all the 
risks that accompany that treatment, or might be incorrectly diagnosed with a serious disease. In other cases, the subject might not receive an 
effective treatment (thereby  
missing out on the benefits that treatment would confer), or might not be diagnosed with the correct disease  
or condition. 
f If an investigational device gives an incorrect diagnosis, the subject might, for example, receive an unnecessary treatment and incur all the 
risks that accompany that treatment, or might be incorrectly diagnosed with a serious disease. In other cases, the subject might not receive an 
effective treatment (thereby missing out on the benefits that treatment would confer),or might not be diagnosed with the correct disease or 
condition. 
Page 56 of 94

Causal relationship: The serious adverse event is associated with the investigational device, comparator, or 
with procedures beyond reasonable doubt when: 
- 
the event is a known side effect of the product category the device belongs to or of similar devices 
and procedures; 
- 
the event has a temporal relationship with investigational device use/application or procedures; 
- 
the event involves a body-site or organ that: 
 
the investigational device or procedures are applied to; 
 
the investigational device or procedures have an effect on; 
- 
the serious event follows a known response pattern to the medical device (if the response pattern is 
previously known); 
- 
the discontinuation of medical device application (or reduction of the level of activation/exposure) 
and reintroduction of its use (or increase of the level of activation/exposure), impact on the serious 
event (when clinically feasible); 
- 
other possible causes (e.g., an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment) have been adequately ruled out; 
- 
harm to the subject is due to error in use; 
- 
the event depends on a false result given by the investigational device used for diagnosis2, when 
applicable.  
 
11.5.2. Adverse Device Effect 
An ADE is an AE related to the use of an investigational medical device. 
This definition includes AEs resulting from insufficient or inadequate IFU, deployment, 
implantation, installation, or operation, or any malfunction of the investigational medical 
device. And this definition includes any event resulting from use error or from intentional 
comparator is a medical device. 
11.5.3. Device Deficiency 
Device deficiency is inadequacy of a medical device related to its identity, quality, durability, 
reliability, safety, or performance. Device deficiency includes malfunction, misuse or use 
errors, and inadequate labeling (ISO14155). 
This includes device deficiencies that might have led to an SAE if: 
 suitable action had not been taken, 
 intervention had not been made, or 
 if circumstances had been less fortunate (these are handled under the SAE reporting 
system). 
 
11.5.4. Adverse Events of Special Interest 
 
 Bleeding-related events, including rebleeding of the bleeding site(s) treated with 
hemostatic patch at any point in time (within 10 minutes of application, prior to 
subject closure, and postoperative), and including hematoma; 
 Thromboembolic events  
 Biloma; and 
 Allergic reaction. 
Page 57 of 94

11.5.5. Foreseeable Adverse Events and Anticipated Adverse Device Effects 
The following events were identified in the risk analysis for GATT-Patch and were found 
acceptable after mitigation steps: 
 Toxic response 
 Thromboembolic event 
 (Re)Bleeding 
 Allergic reaction 
 New surgery 
 Infection (i.e., abscess) 
 Blockage of artery or vein/ischemia of organs 
 Damage of organs and vessels 
 Adhesion to other organs 
 (Pulsatile) hematoma 
 Closing of intestinal track 
 Biloma 
Furthermore, the risk for encapsulated or rolled-up device was identified during the risk 
management, at a lower risk level/incidence. This risk will be further investigated in this 
clinical investigation by means of the 6-weeks follow-up imaging.  
In the first-in-human clinical investigation, the following adverse events occurred with a 
possible relationship to the device: hematoma (n=1/47, 2.1%), biloma (n=1/47, 2.1%) and 
perihepatic abscess (n=1/47, 2.1%). There were no adverse events with a probable or causal 
relationship to the device. While other adverse events occurred, these were considered not 
related to the device. 
A full study report will be written based on the 3 month follow-up data and will be submitted 
to all relevant local country authorities, including a pre-market approval submission to FDA. 
Furthermore, 5 year observational follow-up will be performed to characterize long-term 
safety on all patients undergoing liver resection for liver malignancy or metastases, collecting 
data on local cancer recurrence, disease-free survival, and overall survival. This report will be 
submitted to all relevant local country authorities through an annual progress report (e.g., for 
FDA) or post-market clinical follow-up report (e.g., for countries with EU MDR regulations). 
11.5.6. Serious Adverse Events 
The relevant SAE definitions for this clinical investigation are aligned with MDCG 2020-
10/1 and FDA serious criteria definitions. 
An SAE is any adverse event that led to any of the following: 
 Death 
 Serious deterioration in the health of the subject, that resulted in any of the following: 
a. Life-threatening illness or injury, or 
b.  Disability or permanent impairment of a body structure or a body function, 
     or 
c.  Hospitalization or prolongation of hospitalization, or 
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d.  Medical or surgical intervention to prevent life-threatening illness or injury 
     or permanent impairment to a body structure or a body function, or 
e.  Chronic disease 
 Foetal distress, foetal death, or a congenital physical or mental impairment or birth defect 
 Other important medical event (applicable only for events in the US) 
Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered an SAE. 
Other important medical events that may not be immediately life-threatening or result in 
death or hospitalization, based upon appropriate medical judgment, are considered serious 
AEs (SAEs) if they are thought to jeopardize the subject and/or require medical or surgical 
intervention to prevent one of the outcomes defining an SAE. SAEs are critically important 
for the identification of significant safety problems; therefore, it is important to take into 
investigator believes that an event is serious, the event must be considered serious and 
evaluated by the Sponsor for expedited reporting. 
11.5.7. Serious Adverse Event and Adverse Event Reporting 
An SAE occurring from the time from which the patient is enrolled and randomized until 
discontinuation must be reported to the Syneos Health Safety and Device Vigilance group 
and will be communicated to the Sponsor. Any such SAE due to any cause, whether or not 
related to the investigational device, must be reported within 24 hours of occurrence or when 
the investigator becomes aware of the event. Device Deficiencies and Adverse Events of 
Special Interest also require reporting according to these timelines. Notification can be made 
using the dedicated fax line or email or by completing the adverse event CRF. 
If the investigator contacts the Syneos Health Safety and Device Vigilance group by 
telephone, then a written report must follow within 24 hours and is to include a full 
description of the event and sequelae in the format detailed in the SAE reporting form. 
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must 
be followed up by detailed descriptions later on, including clear and anonymized photocopies 
of hospital case reports, consultant reports, autopsy reports, and other documents when 
requested and applicable. SAE reports must be made whether or not the investigator 
considers the event to be related to the investigational device. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed in 
order to determine the etiology of the problem. The investigator must report all additional 
follow-up evaluations to the Syneos Health Safety and Device Vigilance group within 24 
hours of becoming aware of the additional information or as soon as is practicable. All SAEs 
will be followed up until the investigator and Sponsor agree the event is satisfactorily 
resolved. 
participation in the study is to be followed up until it either resolves, stabilizes, returns to 
baseline values (if a baseline value is available), or is shown to not be attributable to the 
investigational device or procedures.  
Page 59 of 94

The reporting of any SAE to the Competent Authority and/or Ethical Committee has to be 
done by the Sponsor (or Syneos Health) immediately and not later than 2 calendar days after 
awareness. This includes all reportable events, which indicate an imminent risk of death, 
serious injury, or serious illness and that requires prompt remedial action for other subjects, 
users or other persons, or a new finding to it, or as required by the Competent Authority 
and/or Ethical Committee. 
For any other reportable events or a new finding/update to it, the Sponsor (or Syneos Health) 
must report the event to the Competent Authorities and/or Ethical Committee immediately 
and not later than 7 calendar days following the date of awareness by the Sponsor (or Syneos 
Health) of the new reportable event or of new information in relation with an already reported 
event. 
11.5.8. Serious Adverse Device Effect 
A SADE is defined as an ADE that has resulted in any of the consequences characteristic of 
an SAE (ISO14155). 
11.5.9. Unanticipated Serious Adverse Device Effects/ Unanticipated Adverse 
Device Effects 
A USADE which by its nature, incidence, severity or outcome has not been identified in the 
 
Any serious adverse effect on health or safety or any life-threatening problem or death caused 
by, or associated with the GATT-Patch, that was not previously identified in nature, severity, 
or degree of incidence in the CIP, IB or IFU or any other unanticipated serious problem 
associated with the study device that relates to the rights, safety, or welfare of subjects. 
An unanticipated event is one where the nature or severity is not consistent with the 
information in the current Risk Management section of the CIP, IB and IFU. Furthermore, 
reports which add significant information on specificity or severity of a known, already 
documented adverse effect constitute unanticipated events. For example, an event more 
 
Unanticipation will be assessed by a Syneos Health Safety and Device Vigilance and 
reviewed by GATT Technologies.  
The investigator will assess whether an event is causally related to investigational device. The 
whether the event meets the criteria for being reportable as a 7-day or 15-day safety report. 
USADEs that are fatal or life-threatening must be reported to the regulatory authorities and 
the IEC/IRBs (where required) within 7 days after the Sponsor (or Syneos Health) has first 
knowledge of them, with a follow-up report submitted within a further 8 calendar days. Other 
USADEs must be reported to the relevant regulatory authorities and the IEC/IRBs within 15 
calendar days after the Sponsor (or Syneos Health) first has knowledge of them. 
The Sponsor (or Syneos Health) is responsible for reporting USADEs and any other events 
required to be reported in an expedited manner to the regulatory authorities and for informing 
investigators of reportable events, in compliance with applicable regulatory requirements 
within specific timeframes. Investigators will notify the relevant IEC/IRBs of reportable 
events within the applicable timeframes. 
Page 60 of 94

11.5.10. 
Pregnancy 
Women of childbearing potential must have a negative pregnancy test at screening.13 
Following administration of study device, any known cases of pregnancy occurring during 
the 3-month follow-up period after surgery in female subjects will be reported until the 
subject completes the 3-month study visit or withdraws from the study. The pregnancy will 
be reported immediately by faxing/emailing a completed pregnancy report to the Sponsor (or 
designee) within 24 hours of knowledge of the event. The pregnancy will not be processed as 
an SAE. 
If pregnancy occurs within the 3-month follow-up period after surgery, the investigator will 
follow-up with the subject to provide any information on pregnancy outcomes that are 
available during follow-up in the trial (e.g., 3 months for patients undergoing liver surgery for 
other indications than liver malignancy or metastases, and until completion of the pregnancy 
in patients undergoing liver surgery for liver malignancy or metastases) by submitting a 
follow-up pregnancy report to the Sponsor (or designee), which includes information on 
spontaneous or therapeutic abortion (any congenital anomaly detected in an aborted fetus is 
to be documented), stillbirth, neonatal death, or congenital anomaly. 
11.6. 
Independent Adjudication Committee 
An Independent Adjudication Committee (IAC) will review all SAEs and AESIs occurring 
after surgery up to the 3-months study visit for the relatedness with the device and the 
expectedness of the event based on the clinical scenario comprising of patient and procedural 
characteristics. The IAC will meet to review events approximately every 3 months, but at 
least every 6 months; the Sponsor may also choose to schedule additional meetings as 
needed. 
premature termination criteria will be described in a charter. This charter will be approved 
and signed by all parties before study start. 
The IAC will be independent from the Sponsor, the investigators or anyone involved in the 
clinical care of the study subjects. Members will not have scientific, financial or other 
conflict of interest related to the Sponsor or investigators. Potential IAC members will sign a 
non-conflict-of-interest statement in this regard. 
The IAC will function in accordance with applicable regulatory guidelines and the charter. 
 
 
Page 61 of 94

12. STATISTICAL ANALYSIS 
A statistical analysis plan (SAP) will be prepared after the Clinical Investigation Plan is 
approved, or during the approval process, depending on the local country regulations. This 
document will provide further details regarding the definition of analysis variables and 
analysis methodology to address all study objectives. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher (SAS 
Institute, Cary, NC). All data will be listed, and summary tables will be provided. Summary 
statistics will be presented by the treatment group.  
Descriptive statistics will be presented for each variable. Continuous variables will be 
summarized by treatment group using number of subjects, mean, median, standard deviation, 
minimum, and maximum. Categorical variables will be summarized by treatment group using 
frequencies and percentages of subjects in each category. For time-to-event, Kaplan-Meier 
plot will be presented, and 25%, 50% and 75% percentiles and their 95% confidence interval 
will be reported. 
The primary analysis of the primary efficacy endpoint will be conducted on the PP population 
using the Farrington-Manning test with available data. The primary efficacy endpoint will 
also be analyzed on the ITT population as a secondary analysis. Key secondary endpoint will 
be analyzed in both the PP and ITT populations. Consistent results from the analysis of ITT 
and PP datasets are necessary to conclude the non-inferiority of GATT-Patch to TachoSil. 
Other secondary endpoints, and exploratory and safety endpoints will be summarized 
descriptively. 
12.1. 
Study Hypothesis 
The percentage of cases achieving hemostasis at 3 minutes using GATT-Patch is non-inferior 
to TachoSil. Based on the TachoSil FDA submission, the percentage of subjects achieving 
hemostasis at 3 minutes is 75% with TachoSil;5 however, individual studies have reported 
that 80% of subjects achieve hemostasis at 3 minutes.6,8 In the current trial, with an estimated 
80% success and a 10% absolute non-inferiority margin, the statistical null (H0) and 
alternative (H1) hypotheses are the following: 
H0: PG  
-0.10 
H1: PG  PT > -0.10 
Where PG is the true percentage of subjects achieving hemostasis at 3 minutes using GATT-
Patch and PT is the true percentage of subjects achieving hemostasis at 3 minutes using 
TachoSil. 
12.2. 
Determination of Sample Size  
The sample size is powered to determine non-inferiority of GATT-Patch versus TachoSil on 
the primary endpoint of hemostasis at 3 minutes. Based on previous studies, it is assumed that 
80% of subjects achieve hemostasis at 3 min after TachoSil application.2,5,6 Patients will be 
randomized in a 2:1 fashion. Taking into consideration a non-inferiority margin of 10%, and 
assuming that hemostasis is achieved in 92% of patients treated with GATT-Patch.  An 
interim analysis is planned when the primary endpoint is observed for 70% of patients and 
-Fleming alpha-spending function for efficacy stopping boundary, we 
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currently estimate a total sample size of 130 subjects of which 87 patients will undergo 
implantation of GATT-Patch, to achieve 90% statistical power. The success percentage of 
92% is based on the results from the Pilot trial, taking into account a ~5% absolute lower 
performance due to differences in patient population, use, or other factors. The sample size 
will take into account the result of the interim analysis of the primary performance endpoint 
to allow for possible early stopping for success or futility or sample size re-estimation. 
12.3. 
Analysis Population 
Per-Protocol Population (PP) 
The Per-Protocol population will be the cohort for the primary endpoint analysis and includes 
all subjects in ITT population who receive the randomized treatment with GATT-Patch or 
TachoSil, and have an assessment of primary endpoint, and have no major protocol 
deviations. 
Intent-to-Treat Population (ITT) 
The ITT population will include all subjects who are randomized, irrespective of any 
deviation from the protocol or premature discontinuation. The treatment group assignment 
will be designated according to initial randomization. The ITT population will serve as the 
basis for the analysis of efficacy. 
Safety Population 
The safety population will include all randomized subjects who receive treatment with 
GATT-Patch or TachoSil. The treatment group assignment in this population will be defined 
by the treatment actually received. This population will be used for the analysis of safety. 
Evaluable patients are patients that did not meet any of the following withdrawal criteria: 
 Change in SBSS to ineligible (SBSS of 0, 4, or 5) between randomization and 
application of the hemostatic patch; or  
 Death of subject in the time between patch application and patch use. 
 
12.4. 
Efficacy Analysis 
The primary endpoint is the percentage of cases (rate) achieving hemostasis at 3 minutes 
without rebleeding at the 10-minute time point, which will be analyzed using the Farrington-
Manning test. The rate and the 95% exact (Clopper-Pearson) confidence interval for each 
group, and their difference in rate between the treatment group and the corresponding 95% 
Newcombe confidence interval will be reported. The noninferiority will be tested first based 
on these results, and then superiority will be tested. 
A hierarchical testing procedure (alpha = 0.02275) will be applied. The order will be: 
 Non-inferiority of GATT-Patch vs TachoSil for primary endpoint of hemostasis at 3 
minutes without rebleeding at the 10- minutes time point,   
 Superiority of GATT-Patch vs TachoSil for the key secondary endpoint of median 
time to hemostasis,   
 Superiority of GATT-Patch vs TachoSil for the primary endpoint of hemostasis at 3 
minutes without rebleeding at the 10- minutes time point. 
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For the key secondary endpoint, median time to hemostasis, group sample sizes of 87 and 43 
achieve 91% power to reject the null hypothesis of equal group response distributions when 
the effect size is as low as 0.68 and the significance level is 0.02275 using a one-sided 
Wilcoxon-Mann-Whitney test. The effect size is the probability that an observation from 
GATT-Patch group is less than an observation from TachoSil group and was estimated to be 
0.93, derived from Figure 2 in Öllinger et. al. (2015).3  
The time to hemostasis will be censored at 10 minutes for the case which does not achieve 
hemostasis by 10 minutes. The uncensored time to hemostasis, as well as the censored time to 
hemostasis (with censored patients having a 10-minute time to hemostasis) will be 
summarized descriptively. The time to hemostasis will furthermore be analyzed using Log-
rank test. Kaplan-Meier plot will also be presented, and 25%, 50% (median) and 75% 
percentiles and their 95% confidence interval will be reported. The Cox proportional hazard 
model may be used to include some prognostic variables and baseline characteristics as 
covariates. 
The primary analysis for the primary endpoint and the key secondary endpoint will be 
performed in PP population. They will also be analyzed in ITT population as secondary 
analysis.   
The other secondary endpoints and exploratory endpoints will be summarized descriptively 
by treatment groups. 
12.5. 
Safety Analysis 
All reported AEs will be coded using the most recent version of the Medical Dictionary for 
Regulatory Activities (MedDRA). The incidence of treatment-emergent AEs (TEAEs; events 
with onset dates on or after the study device) will be included in incidence tables. Events with 
missing onset dates will be included as treatment-emergent. If a subject experiences more 
than 1 occurrence of the same AE, the occurrence with the greatest severity and the closest 
association with the study device will be used in the summary tables. Serious adverse events, 
treatment-related AEs and AEs causing discontinuation will be tabulated. All AEs will be 
listed by subject, along with information regarding onset, duration, relationship and severity 
to study drug, action taken with study drug, treatment of event, and outcome. 
Clinical laboratory data and vital signs will be summarized using descriptive statistics, 
including mean values and mean change from baseline values, as well as numbers of subjects 
with values outside limits of the normal range at each time point. 
Summary tables will be provided for concomitant medications initiated during the study 
period. 
The safety evaluation will report the cumulative incidence of all adverse events (AEs or 
SAEs) and by severity through 12 weeks post-treatment for each treatment group. The 
numbers and percentages of subjects with at least one adverse event, at least one serious 
adverse event, at least one treatment-related adverse event will be reported and compared 
between the groups. The results of the imaging at 6 weeks will also be compared between 
groups. 
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12.6. 
Other Analysis 
The primary and key secondary endpoints may be analyzed based on all treated target 
bleeding sites. 
12.6.1. Subgroup Analysis 
For the primary endpoint, descriptive statistics of number and percent of patients meeting the 
primary endpoint in each randomized group will be presented separately for each 
investigational site. Homogeneity across sites in the primary endpoint will be checked based 
on deviance from logistic regression with achieving the primary endpoint (yes/no) as the 
dependent variable. 
The following patient subgroups are defined for prespecified analyses: 
 Age  
 Sex (male/female) 
 SBSS (1/2/3) 
 Type of bleeding (venous/arterial/mixed) 
 Type of hepatic parenchyma (normal/cirrhotic/staetotic) 
 Portal hypertension (yes/no) 
 Child Pugh classification (A/B/C/NA) 
 MELD-Na Score (<17 / 17-20 / 21-22 / 23-26 / 27-
 
 Renal function (eGFR >90 / eGFR 60-90 / eGFR 30-60 / eGFR 15-30 / chronic 
dialysis) 
 Antithrombotic medication use (yes/no) 
 Concomitant chemotherapy (yes/no) 
 Concomitant steroid therapy (yes/no) 
A subgroup analysis for safety will be performed among groups with or without surgical 
drains on the presence of fluid collections, specifically biloma formation. 
12.6.2. Interim Analysis 
This study will include an FDA review of data after the enrolment of 10 US-based patients 
from 2 US-based sites, which will be made available to other relevant to other local country 
authorities for review upon request. No formal statistical analyses will be performed on these 
data. 
After FDA approval to continue, the study utilizes an adaptive design with an interim 
analysis planned for the purposes of stopping the trial early for success or futility and for 
sample size re-estimation. The interim analysis will be performed once 70% (n=91) of the 
planned evaluable subjects in total are treated. To account for multiple testing and control the 
overall Type I error rate of the study at one-sided 0.025 level, a group-sequential design will 
be used based on the Lan-DeMets approach with an O'Brien-Fleming alpha-spending 
function. Based on this method, the efficacy goal of GATT-Patch with a 10% absolute non-
inferiority margin compared to the standard of care, TachoSil, regarding the percentage of 
cases achieving hemostasis at 3 minutes, will be assessed at the interim review. A Farrington-
Manning test of non-inferiority difference between two proportions at a one-sided 0.00738 
significance level will be performed at the interim analysis. If the statistical analysis of the 
Page 65 of 94

primary efficacy endpoint at the interim review yields a one-sided p-value less than 0.00738: 
(1) a superiority analysis will subsequently be performed using two-sample t-test at a one-
sided 0.00738 significance level, and (2) the IDMC may recommend stopping the trial for 
successful efficacy if non-inferiority is met. If the one-sided p-value is not less than 0.00738, 
then a sample size re-estimation (SSR) based on conditional power (probability of study 
success given the interim results) may be conducted to determine if the sample size will be 
increased. The interim decision rules will be: 
 If the p-value is less than 0.00738, the IDMC may recommend stopping the trial for 
successful efficacy; otherwise 
 If the conditional power is greater than 90%, the study will continue as planned; 
 If the conditional power is between 50% and 90%, then the sample size will be re-
estimated to achieve the 90% conditional power with the constraint of the maximum 
allowed sample size of 200; 
 If the conditional power is less than 50%, the Sponsor may choose to continue the 
study as planned though it is less likely to be successful, or terminate the study. 
When the conditional power is greater than 50%, a sample size increase will not require an 
additional penalty to the final significance (alpha) level according to Chen-Demets-Lan 
method. If the study is not stopped for successful efficacy, the study will continue to the 
sample size determined by the SSR and the final efficacy analysis will be evaluated according 
to the hierarchical testing procedure detailed in section 12.1.  
Further details will be provided in the SAP. 
12.6.3. Five-year follow-up 
Data on five-year survival, cancer recurrence, and disease-free survival outcomes of all 
patients treated for liver malignancy or metastases will be provided in a tabulated manner 
with descriptive statistics. This observational follow-up will not be in direct contact with the 
physician. The review will be submitted to all relevant local country authorities through an 
annual progress report (i.e., for FDA) or post-market clinical follow-up report (i.e., for 
countries with EU MDR regulations). 
12.7. 
Independent Data Monitoring Committee 
Any safety concerns, serious adverse device effects (SADE), or death during the clinical 
investigation will be immediately referred, on a case-by-case basis, to the blinded 
Independent Data Monitoring Committee for safety review. The Medical Monitor, the 
unblinded team member, will monitor all emerging safety issues against pre-defined stopping 
rules of the clinical investigation. These stopping rules only apply to the investigational 
treatment group, (i.e., patients having received GATT-Patch). 
The stopping rules are: 
 One SADE classified as grade 5 on the Clavien-Dindo scale of surgical 
complications14 (i.e., resulting in death and confirmed to be related to study device 
intraoperatively or post-operatively during the autopsy (if applicable)) OR 
 Three SADEs classified on the Clavien-Dindo scale of surgical complications14 as: 
Page 66 of 94

o Grade 3b (intervention under general anesthesia) requiring re-laparotomy for 
the treatment of the event, e.g. re-bleeding or abscess formation from the 
target bleeding site (TBS), or angiography for the detection and treatment of 
post-operative bleeding from the TBS 
o Grade 4  (life-threatening complication requiring IC/ICU management), 
confirmed to be related to the study device   
A further investigation by the sponsor will be conducted to determine if the study requires 
early termination.  
le, meeting schedule, functioning recommendations, and 
premature termination criteria will be described in a charter.  
The IDMC will be independent from the Sponsor, the investigators or anyone involved in the 
clinical care of the study subjects. Members will not have scientific, financial or other 
conflict of interest related to the Sponsor or investigators. Potential IDMC members will sign 
a non-conflict-of-interest statement in this regard. 
The IDMC will function in accordance with applicable regulatory guidelines and the charter. 
 
 
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13. STUDY MANAGEMENT 
13.1. 
Approval and Consent 
13.1.1. Regulatory Guidelines 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant regulations, as set forth in Parts 50, 56, 812, Subpart D, of Title 
21 of the United States Code of Federal Regulations (CFR), ISO14155 (Clinical Investigation 
of Medical Devices for Human Subjects Good Clinical Practice), and according to the 
appropriate regulatory requirements in the countries where the study was conducted. 
13.1.2. Institutional Review Board/Independent Ethics Committee 
Conduct of the study must be approved by an appropriately constituted IEC/IRB. Approval is 
required for the study Clinical Investigation Plan, Clinical Investigation Plan amendments (if 
applicable), IB or IFU, ICFs, recruitment material and subject information sheets and other 
subject-facing material. Additionally, the notification of changes to site personnel or any 
other relevant changes to the conduct of the study will follow local country regulatory 
requirements. 
13.1.3. Informed Consent 
The investigator is responsible for assuring that written informed consent is obtained from 
each subject prior to participation in the clinical investigation. Should the investigator 
delegate the responsibility of conducting the informed consent process to a designee, the 
investigator must ensure and document appropriate training of the authorized designee. 
The investigator will use an approved ICF that was prepared in accordance with this CIP, 
 
Subjects must be fully counselled and informed of their options, risks and benefits, and 
should have every opportunity to ask questions about participation in the clinical 
investigation. This process includes a thorough explanation of the subject information letter 
and ICF that the subject will be asked to sign, acknowledging that they understand and 
consent to participate in the clinical investigation. 
While an investigator may discuss availability of the investigation with a prospective subject 
without first obtaining consent, informed consent must always be obtained from a subject 
prior to initiation of any clinical procedures dictated by the CIP that are performed solely for 
the purpose of determining eligibility to participate in the clinical investigation. A copy of the 
signed statement of informed consent will be provided to the subject. 
If new information regarding the investigational device becomes available and/or the CIP 
changes and this information can significantly affect a subject's future health and medical 
care, subjects will be informed of the information and may be asked to sign a revised ICF. A 
subject may withdraw or discontinue participation at any time during the clinical 
investigation. 
13.2. 
Data Handling 
Data will be collected and recorded using a validated electronic data capture (EDC) system 
that meets all requirements as set forth in the FDA and ISO standards. An audit trail is 
available for tracking all information that the EDC user enters, modifies or deletes. One 
Page 68 of 94

electronic copy of the final database will be archived in the electronic database of Syneos 
Health and another copy will be stored at GATT Technologies BV. 
The investigator or its designee will perform primary data collection drawn from original 
documents (printed, optical or electronic document containing source data), also referred to 
as source documents. 
It is the responsibility of the investigator to ensure that the site files are maintained in 
accordance with ISO14155 - Good Clinical Practice for Medical Devices and applicable 
regulations. 
Any data to be recorded directly on the eCRFs (to be considered as source data) will be 
identified at the start of the study. Data reported on the eCRF that are derived from source 
documents should be consistent with the source documents, or the discrepancies must be 
explained. See also Section 13.6 
Clinical data will be entered by site personnel on eCRFs for transmission to the Sponsor. 
Data on eCRFs transmitted via the web-based data system must correspond to and be 
supported by source documentation maintained at the study site, unless the study site makes 
direct data entry to the databases for which no other original or source documentation is 
maintained. In such cases, the study site should document which eCRFs are subject to direct 
data entry and should have in place procedures to obtain and retain copies of the information 
submitted by direct data entry. All study forms and records transmitted to the Sponsor must 
only include coded identifiers such that directly identifying personal information is not 
transmitted. The primary method of data transmittal is via the secure, internet-based EDC 
system maintained by Syneos Health. Access to the EDC system is available to only 
 internet web site, where a user unique assigned username and 
password are required for access. 
Electronic CRFs will be considered complete when all missing and/or incorrect data have 
been resolved. 
13.2.1. Source Documents 
Source documents are considered to be all information in original records and certified copies 
of original records of clinical findings, observations, data, or other activities in a clinical 
study necessary for the reconstruction and evaluation of the study. The investigator will 
provide direct access to source documents and/or source data in the facilitation of trial-related 
monitoring, audits, review by IECs/IRBs, and regulatory inspections. 
The investigator/institution should maintain adequate and accurate source documents and trial 
records th
should be attributable, legible, contemporaneous, original, accurate, and complete. Changes 
to source data should be traceable, not obscure the original entry, and be explained if 
necessary. 
13.2.2. Record Retention 
The investigator maintains all clinical investigation records for the minimum time required in 
the country in which the clinical investigation is conducted, which will be at least 15 years. 
Records to be retained may include: all correspondence, documentation of device receipt and 
Page 69 of 94

amendments, Investigator Brochure, and dates and reasons for any deviations to the CIP or as 
otherwise specified by the applicable laws and regulations. 
Furthermore, the documentation will be kept by GATT Technologies BV for a period of at 
least 15 years after the clinical investigation with the device in question has ended, or, in the 
event that the device is subsequently placed on the market, at least 10 years after the last 
device has been placed on the market. 
For the United States only: The investigator agrees to comply with all applicable federal, 
state, and local laws and regulations relating to the privacy of subject health information, 
including, but not limited to, the Standards for Individually Identifiable Health Information, 
45 CFR, Parts 160 and 164 (the Health Insurance Portability Accountability Act of 1996 
[HIPAA] Privacy Regulation). The investigator shall ensure that study subjects authorize the 
use and disclosure of protected health information in accordance with HIPAA Privacy 
Regulation and in a form satisfactory to the Sponsor. 
13.3. 
Monitoring 
The study will be monitored according to Syneos Healths´ monitoring plan to ensure that it is 
conducted and documented properly according to the Clinical Investigation Plan, ISO14155, 
and all applicable regulatory requirements. 
Monitoring visits, on-site and remote (telephone) and contacts will be made at appropriate 
times during the study. The PI will ensure he/she and adequate site personnel are available 
throughout the study to collaborate with clinical monitors. Clinical monitors must have direct 
access to source documentation in order to check the completeness, clarity, and consistency 
of the data recorded in the eCRFs for each subject. 
The investigator will make available to the clinical monitor all source documents and medical 
records necessary to review Clinical Investigation Plan adherence and eCRFs. In addition, the 
investigator will work closely with the clinical monitor and as needed, provide them 
appropriate evidence that the study is being conducted in accordance with the Clinical 
Investigation Plan, applicable regulations, and ISO14155 guidelines. 
13.4. 
Quality Control and Quality Assurance 
The Sponsor or its designee will perform the quality assurance and quality control activities 
of this study; however, responsibility for the accuracy, completeness, security, and reliability 
of the study data presented to the Sponsor lies with the investigator generating the data. 
13.5. 
Clinical Investigation Plan Amendment and Clinical Investigation Plan 
Deviation 
13.5.1. Clinical Investigation Plan Amendment 
Investigators may not modify (amend) this CIP without obtaining written concurrence of the 
Sponsor, involved ethics committee(s), and applicable regulatory authorities. 
Amendments to the Clinical Investigation Plan that entail corrections of typographical errors, 
clarifications of confusing wording, changes in study personnel, and minor modifications that 
have no effect on the safety of subjects or the conduct of the study will be classed as 
administrative amendments and will be submitted to the IEC/IRB for information only. The 
Sponsor will ensure that acknowledgement is received and filed. Amendments that are 
classed as substantial amendments must be submitted to the appropriate regulatory authorities 
Page 70 of 94

and the IECs/IRBs for approval and will not be implemented at sites until such approvals are 
received other than in the case of an urgent safety measure. 
13.5.2. Clinical Investigation Plan Deviations 
Investigators may not deviate from this CIP without first receiving approval in writing from 
the Sponsor, involved ethics committee(s), and applicable regulatory authorities, except to 
protect the rights, safety and well-being of human subjects under emergency circumstances. 
Such deviations shall be documented and reported to the Sponsor and the ethics committee as 
soon as possible. All deviations will be documented on eCRFs. The use of waivers from the 
CIP is prohibited. 
13.6. 
Ethical Considerations 
This study will be conducted in accordance with this Clinical Investigation Plan, the accepted 
version of the Declaration of Helsinki and/or all relevant federal regulations, as set forth in 
Parts 50, 56, 812, Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and 
in compliance with ISO14155 (Clinical Investigation of Medical Devices for Human 
Subjects Good Clinical Practice), the Medical Device Directive EC/93/42 guidelines. 
IECs/IRBs will review and approve this Clinical Investigation Plan and the ICF. All subjects 
are required to give written informed consent before participation in the study. 
13.7. 
Financing and Insurance 
Before the study commences, the Sponsor (or its designee) and the investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study. This agreement 
will be documented in a financial agreement (or as part of the clinical trial agreement) that 
will be signed by the investigator (or the institution signatory) and the Sponsor (or its 
designee). 
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The Sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations. 
13.8. 
Publication Policy/Disclosure of Data 
After closure of the clinical investigation, the results will be summarized in a Clinical 
Investigation Report, which will be submitted to the investigators, ethics committee(s) and 
appropriate regulatory authorities. This Clinical Investigation Report will include a summary 
of the results based on a statistical evaluation and clinical assessment. 
GATT Technologies BV may at any time publish the results of and information pertaining to 
the investigation subject only to compliance with regulatory requirements pertaining to 
patient protected health information. The conditions under which an investigator may publish 
results from this clinical investigation in any form are defined in detail in the clinical trial 
agreement. 
Irrespective of the outcome of the clinical investigation, within one year of the end of the 
clinical investigation or within three months of the early termination or temporary halt, 
GATT Technologies BV will submit to the Member States in which a clinical investigation 
was conducted a Clinical Investigation Report. 
Page 71 of 94

The clinical study will be registered in a public database (clinicaltrials.gov) and a summary of 
the results will be posted in this database once they become available. 
 
 
Page 72 of 94

14. REFERENECES  
 
1. Wells, C. e. (2020, Oct). Haemostatic Efficacy of Topical Agents During Liver 
Resection: A Network Meta-Analysis of Randomised Trials. World Journal of 
Surgery, 44(10). doi:10.1007/s00268-020-05621-z 
2. Brustia, R. G. (2016, Oct). An update on topical haemostatic agents in liver surgery: 
systematic review and meta analysis. Journal of Hepatobiliary Pancreat Science, 
23(10). doi:10.1002/jhbp.389 
3. Öllinger, R. e. (2015, July). A multicentre, randomized clinical trial comparing the 
Veriset
 haemostatic patch with fibrin sealant for the management of bleeding 
during hepatic surgery. HPB, 15(7). doi:10.1111/hpb.12009 
4. Vagg, D. T. (2020, July). The Principles of Liver Resection. Surgery (Oxford), 38(8). 
doi:10.1016/j.mpsur.2020.06.005 
5. Kozek-Langenecker, S. e. (2017, Jun). Management of severe perioperative bleeding: 
guidelines from the European Society of Anaesthesiology: first update 2016. 
European Journal of Anaesthesiology, 34(6). doi:10.1097/EJA.0000000000000630 
6. Lewis, K. e. (2018, May). Clinical effectiveness and versatility of a sealing 
hemostatic patch (HEMOPATCH) in multiple surgical specialties. Expert review of 
medical devices, 15(5). doi:10.1080/17434440.2018.1464909 
7. Spotnitz, W. e. (2018, Mar). The SPOT GRADE: a new method for reproducibly 
quantifying surgical wound bleeding. Spine, 48(11). doi:10.1155/2014/203943 
8. 
the efficacy and safety of fibrin sealant grifols as an adjunct to hemostasis as 
compared to cellulose sheets in hepatic surgery resections. Journal of Gastrointestinal 
Surgery, 22(11). doi:10.1007/s11605-018-3852-4 
9. Bochicchio, G. e. (2015, Jan). The FINISH-3 trial: a phase 3, international, 
randomized, single-blind, controlled trial of topical fibrocaps in intraoperative 
surgical hemostasis. Journal of the American College of Surgeons, 220(1). 
doi:10.1016/j.jamcollsurg.2014.09.019 
10. Genyk, Y. e. (2016, Dec). Fibrin sealant patch (TachoSil) vs oxidized regenerated 
cellulose patch (Surgicel Original) for the secondary treatment of local bleeding in 
patients undergoing hepatic resection: a randomized controlled trial. Journal of the 
American College of Surgeons, 222(3). doi:10.1016/j.jamcollsurg.2015.12.007 
11. Moench, C. e. (2014, Aug). Randomized controlled multicenter trial on the 
effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound 
fibrin sealant during liver resection (ESSCALIVER study, NCT00918619). 
Langenbecks Arch Surg,, 399(6). doi:0.1007/s00423-014-1203-9 
12. Verhoef, C. e. (2015, Apr). Fibrocaps for surgical hemostasis: two randomized, 
controlled phase II trials. J Surg Res., 194(2). doi:10.1016/j.jss.2014.12.011 
13. Agencies, H. o. (2014). Clinical Trial Facilitation Group page. Recommendations 
related to contraception and pregnancy testing in clinical trials. Retrieved Nov 01, 
2022, from Heads of Medicines Agencies: 
https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf?fbc
lid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80N-
5ME6pkBb1UHvFsTwqlQ 
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14. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new 
proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann 
Surg 2004;140:205-13. 
 
 
Page 74 of 94

15. APPENDICES 
APPENDIX 1 User satisfaction questionnaire 
APPENDIX 2 Physician Treatment Preference Assessment  
APPENDIX 3 describes the training and testing requirements for the Surface Bleeding 
Severity Scale Report (SBSS) 
APPENDIX 4 describes the safety reporting requirements for Germany. 
APPENDIX 5 describes the safety reporting requirements for The Netherlands. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 75 of 94

15.1.1. APPENDIX 1. User satisfaction questionnaire 
System/device: 
GATT-Patch 
Date of use: 
 
Location (Hospital): 
 
Use environment: 
Operating room 
Name participant: 
 
Function participant: 
 
Name GATT Technologies* 
representative:  
 
Function GATT Technologies* 
representative:   
 
*If applicable 
 
MATERIALS LIST: 
- 
GATT-Patch 
- 
Instructions for use (IFU) 
- 
Implant cardg  
- 
Surgical gloves 
- 
Gauzes 
- 
Saline 
 
 
 
 
 
 
 
 
 
 
 
 
g The manufacturer needs to provide an Implant Card for implantable medical devices, according to  
requirements of Regulation (EU) 2017/745 (MDR), article 18. The card can only be provided to patients after 
the final study assessment and should remain in possession at site until then. 
Page 76 of 94

A. SUS  System Usability Scale 
 
 
 
Strongly disagree 
 
Strongly agree 
1. 
I think that I would like to use this device frequently  
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
2. 
I found the device unnecessarily complex 
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
3. 
I thought the device was easy to use 
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
4. 
I think that I would need the support of a technical 
person to be able to use this device. 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
5. 
I found the various functions in this system were well 
integrated. 
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
6. 
I thought there was too much inconsistency in this 
system  
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
7. 
I would imagine that most people would learn to use 
this system very quickly. 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
8. 
I found the system very cumbersome to use. 
 
 
 
 
 
 
Page 77 of 94

 
 
1 
2 
3 
4 
5 
 
9. 
I felt very confident using the system. 
 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
10. 
I needed to learn a lot of things before I could get 
going with this system 
 
 
 
 
 
 
 
1 
2 
3 
4 
5 
B. Medical Device specific questions 
1. On the non-sterile packaging of GATT-Patch, it is clear what the storage conditions need to be. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
2. On the packaging of GATT-Patch, it is clear what the expiration date is. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
3. It is clear how to safely open the packaging, without damaging GATT-Patch. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
4. It is clear that GATT-Patch should be used within 1 hour after opening the blister. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
5. It is clear on which organs GATT-Patch is allowed to be used. 
 
Page 78 of 94

Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
6. It is clear on which organs GATT-Patch is not allowed to be used. 
 
Strongly disagree 
 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
7. It is clear for what severity of bleeding GATT-Patch can be used.  
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
8. It is clear what contraindications of a patient prohibit use of GATT-Patch.  
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
9. The information in the instructions for use is sufficient. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
10. The packaging is easy to open without damaging GATT-Patch. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
11. The size of GATT-Patch is adequate for its intended purpose. 
Page 79 of 94

 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
12. A dry GATT-Patch does not stick to dry gloves and instruments (e.g. tweezers). 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
13. GATT-Patch is easy to cut with dry scissors. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
14. GATT-Patch can be handled with dry tweezers without damaging/fragmentating. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
15. It is clear that GATT-Patch should be applied with a wet gauze for an initial period of 30 seconds of 
pressure. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
16. It is clear that GATT-Patch should be applied overlapping the margins of the bleeding surface by at 
least 1 cm. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
Page 80 of 94

1 
2 
3 
4 
5 
 
 
17. GATT-Patch is pliable on irregular tissue when applied with a wet gauze. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
18. After application, the wet gauze can be carefully and safely removed without damaging GATT-
Patch. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
19. GATT-Patch stays in place after application. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
20. It is easy to ensure that GATT-Patch is fully hydrated after application. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
21. It is clear how to apply a GATT-Patch (partly) on top of another GATT-Patch. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
22. The maximum number of GATT-Patches used in a patient is clear.  
 
Strongly disagree 
 
Strongly agree 
Page 81 of 94

 
 
 
 
 
1 
2 
3 
4 
5 
 
23. The blue color helps to visualize GATT-Patch after application. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
24. It is safe to remove excess non-adherent GATT-Patch without damaging adherent GATT-Patch. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
25. GATT-Patch can be used intuitively. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
26. I feel confident that GATT-Patch stops a bleeding. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
27. I feel confident that GATT-Patch can be used safely. 
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
28. GATT-Patch is easy to be used/handled. 
 
Page 82 of 94

Strongly disagree 
 
Strongly agree 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
29. It is clear what to do with the Implant Card.  
 
Strongly disagree 
 
Strongly agree 
 
 
 
 
 
 
1 
2 
3 
4 
5 
 
Your comments to the design of the device or labelling are much appreciated: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
_________________________________ 
Signature of user 
Page 83 of 94

 
 
_________________________________ 
Date and location of signature 
 
Page 84 of 94

15.1.2. Physician Treatment Preference Assessment 
 
INTRODUCTION 
While there are many approved hemostatic products on the market to be used as an adjunct to 
hemostasis, their use varies between surgeons, in part due to physician preference for certain 
products. Among hemostatic patches, TachoSil is the current global market leader and is often 
considered to be the standard of care for bleeding during liver surgery.  
To evaluate the safety and efficacy of GATT-Patch for hemostasis during liver surgery, the current 
clinical investigation compares GATT-Patch to TachoSil in minimal, mild or moderate bleeding of the 
liver. In order to evaluate the use of GATT-Patch, a questionnaire has been developed to determine 
the preference of physicians and involved operating room staff towards TachoSil or GATT-Patch, on 
the basis of certain product characteristics.  
Your answers to this questionnaire should be based on your experience in using TachoSil and GATT-
Patch in this clinical investigation. For each topic, you need to indicate your (i) strong preference for 
TachoSil, (ii) slight preference for TachoSil, (iii) neutrality, (iv) slight preference for GATT-Patch, or (v) 
strong preference for GATT-Patch. 
 
Page 85 of 94

Preference questions 
 
Indicate your preference for TachoSil or GATT-Patch for each of the below comments characteristics: 
 
 
 
 
Strong 
preference 
for  
TachoSil 
Slight 
preference 
for  
TachoSil 
Neutral 
Slight 
preference 
for 
GATT-
Patch 
Strong 
preference 
for 
GATT-
Patch 
1. Opening the package without damaging product  
 
 
 
 
2. Opening package and present to sterile field 
 
 
 
 
 
3. Ability to use product straight out of the package  
 
 
 
 
4. Sticking to dry gloves and instruments 
 
 
 
 
 
5. Handling/cutting with dry instruments without 
damaging the patch 
 
 
 
 
 
6. Time of pressure when applied to tissue 
 
 
 
 
 
7. Conforming to irregular tissue 
 
 
 
 
 
8. Flexibility/pliability of the product 
 
 
 
 
 
9. Ease of wet gauze removal after application 
 
 
 
 
 
10. Product adhesion to tissue after application 
 
 
 
 
 
11. Staying in place after application 
 
 
 
 
 
12. Ease-of-use and intuitively to use product  
 
 
 
 
 
13. The hemostatic performance 
 
 
 
 
 
14. Time to hemostasis 
 
 
 
 
 
15. Severity of bleeding that the product can handle  
 
 
 
 
16. Hemostasis in patients with coagulopathic 
(hereditary or medication-related) conditions 
 
 
 
 
 
17. Hemostasis on a cirrhotic liver 
 
 
 
 
 
18. Level of assurance that no rebleed will occur 
 
 
 
 
 
19. The safety of the product 
 
 
 
 
 
20. My overall product preference  
 
 
 
 
 
Page 86 of 94

Your remarks about the differences between products are much appreciated: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
_________________________________ 
Signature of user 
 
_________________________________ 
Date and location of signature 
Page 87 of 94

15.1.3. APPENDIX 3. Surface Bleeding Severity Scale (SBSS) Training and 
Testing 
Report DHF-01-SR-107 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 88 of 94

15.1.4. APPENDIX 4. Safety Reporting Germany 
Regulations: 
The below definitions, for a clinical trial being subject to authorisation, are provided in the European 
Regulation 2017/745  Medical Device Regulation (MDR):  
 
(a) death, 
(b) serious deterioration in the health of the subject, that resulted in any of the following: 
(i) life-threatening illness or injury, 
(ii) permanent impairment of a body structure or a body function, 
(iii)  hospitalisation or prolongation of patient hospitalisation, 
(iv) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
(v) chronic disease, 
(c) foetal distress, foetal death or a congenital physical or mental impairment or birth defect. 
, durability, reliability, safety 
or performance of an investigational device, including malfunction, use errors or inadequacy in 
 
  
 
  
Roles and Responsibilities: 
Sponsor: 
1. Trains all Investigators on the SAE and Device Deficiency reporting procedures in compliance with 
the CIP and in compliance with applicable regulations (Germany follows European Regulation 
2017/745  MDR). 
2. Reports without delay to BfArM (European Regulation 2017/745  Article 80  Paragraph 2): 
a) All SAEs that occurred at a German investigational site and that has a causal relationship 
with the investigational device, the comparator or the investigation procedure or where such 
causal relationship is reasonably possible 
b) All Device Deficiency that occurred at a German investigational site and that might have 
led to a serious adverse event if appropriate action had not been taken, intervention had not 
occurred, or circumstances had been less fortunate 
c) Any new findings in relation to any event referred to in points (a) and (b). 
3. Reports without delay to BfArM (European Regulation 2017/745  Article 80  Paragraph 3) any 
events described in above paragraph 2 and that occurred in third countries in which a clinical 
investigation is performed under the same CIP. 
4. Forwards without delay to BfArM any follow-up and final reports of events described in above 
paragraph 2 . 
5. Reports without delay to the National Competent Authorities (NCAs) of all other Member States 
participating in the clinical trial, any events described in above paragraph 2 and that occurred at a 
German investigational site (European Regulation 2017/745  Article 80  Paragraph 4). 
Page 89 of 94

6. Any events described in above paragraph 2 will be reported by the sponsor to BfArM as per the 
applicable reporting requirements specified on the BfArM webpage www.bfarm.de. 
7. Sponsor will report to BfArM  and relevant NCAs where the clinical study has commenced, all 
reportable events (occurred worldwide) by EUDAMED (once fully functional) or Clinical 
Investigation Summary Safety Report Form MDCG 2020-10-2. 
8. Additionally, sponsor will report to BfArM quarterly summary of assessment of any events 
described in above paragraph 2 as per the applicable reporting requirements specified on the BfArM 
webpage www.bfarm.de. 
  
Site/ Investigator: 
1. Record all SAEs occurring in the trial within 24 hours on the appropriate Adverse Event pages in 
 
2. In addition, the investigator completes all relevant eCRF pages that provide further relevant 
detailed information regarding the event, e.g. concomitant medications and laboratory test results. 
3. The entry of a serious AE in the eCRF by the investigator will trigger a notification to the CRO 
who will inform the sponsor of the SAE within one business day of receipt. 
 
Timelines: 
Reporting to BfArM of events described above (European Regulation 2017/745  Article 80  
Paragraph 2) that occurred in Germany and in all other countries where the clinical trial is performed 
should be done according to the following timelines: 
 
Reportable event with imminent risk of death, serious injury, or serious illness and that 
require prompt remedial action for other patients/subjects, users or other persons or a new 
finding to it: immediately but not later than 2 calendar days after awareness by sponsor of a 
new reportable event or of new information in relation with an already reported event 
 
 
Any other reprotable event or a new finding / update to it: immediately but not later than not 
later than 7 calendar days after awareness by sponsor of a new reportable event or of new 
information in relation with an already reported event 
 
Privacy Statement 
The Sponsor (or its designee) and the investigator (or the institution, as applicable) shall treat all 
information as confidential and shall ensure the protection of the clinical trial subjects fundamental 
right to integrity and privacy through compliance with applicable data protection laws including but 
not limited to the Regulation (EU) 2016/679 on the protection of natural persons with regard to the 
processing of personal data and the free movement of such data (GDPR), the German Data Protection 
Act (BDSG) and the Data Protection Act of Baden-Württemberg (LDSG). 
 
15.1.5. APPENDIX 5. Safety Reporting The Netherlands 
Regulations: 
Page 90 of 94

The below definitions, for a clinical trial being subject to authorisation, are provided in the European 
Regulation 2017/745  Medical Device Regulation (MDR):  
following: 
(a) death, 
(b) serious deterioration in the health of the subject, that resulted in any of the following: 
(i) life-threatening illness or injury, 
(ii) permanent impairment of a body structure or a body function, 
(iii)  hospitalisation or prolongation of patient hospitalisation, 
(iv) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
(v) chronic disease, 
(c) foetal distress, foetal death or a congenital physical or mental impairment or birth defect. 
or performance of an investigational device, including malfunction, use errors or inadequacy in 
 
  
 
  
Roles and Responsibilities: 
Sponsor: 
1. Trains all Investigators on the SAE and Device Deficiency reporting procedures in compliance with 
the CIP and in compliance with applicable regulations (Germany follows European Regulation 
2017/745  MDR). 
2. Reports without delay to CCMO (European Regulation 2017/745  Article 80  Paragraph 2): 
a) All SAEs that occurred at a Netherlands investigational site and that has a causal relationship 
with the investigational device, the comparator or the investigation procedure or where such 
causal relationship is reasonably possible 
b) All Device Deficiency that occurred at a Netherlands investigational site and that might have 
led to a serious adverse event if appropriate action had not been taken, intervention had not 
occurred, or circumstances had been less fortunate 
c) Any new findings in relation to any event referred to in points (a) and (b). 
3. Reports without delay to CCMO (European Regulation 2017/745  Article 80  Paragraph 3) any 
events described in above paragraph 2 and that occurred in third countries in which a clinical 
investigation is performed under the same CIP. 
4. Forwards without delay to CCMO any follow-up and final reports of events described in above 
paragraph 2 . 
5. Reports without delay to the National Competent Authorities (NCAs) of all other Member States 
participating in the clinical trial, any events described in above paragraph 2 and that occurred at a 
Netherlands investigational site (European Regulation 2017/745  Article 80  Paragraph 4). 
6. Any events described in above paragraph 2 will be reported by the sponsor to CCMO as per the 
applicable reporting requirements specified on the CCMO webpage www.ccmo.nl. 
7. Sponsor will report to CCMO  and relevant NCAs where the clinical study has commenced, all 
reportable events (occurred worldwide) by EUDAMED (once fully functional) or Clinical 
Investigation Summary Safety Report Form MDCG 2020-10-2. 
Page 91 of 94

 
Site/ Investigator: 
1. Record all SAEs occurring in the trial within 24 hours on the appropriate Adverse Event pages in 
 
2. In addition, the investigator completes all relevant eCRF pages that provide further relevant 
detailed information regarding the event, e.g. concomitant medications and laboratory test results. 
3. The entry of a serious AE in the eCRF by the investigator will trigger a notification to the CRO 
who will inform the sponsor of the SAE within one business day of receipt. 
 
Timelines: 
Reporting to CCMO of events described above (European Regulation 2017/745  Article 80  
Paragraph 2) that occurred in Netherlands and in all other countries where the clinical trial is 
performed should be done according to the following timelines: 
 
Reportable event with imminent risk of death, serious injury, or serious illness and that 
require prompt remedial action for other patients/subjects, users or other persons or a new 
finding to it: immediately but not later than 2 calendar days after awareness by sponsor of 
a new reportable event or of new information in relation with an already reported event 
 
Any other reprotable event or a new finding / update to it: immediately but not later than 
not later than 7 calendar days after awareness by sponsor of a new reportable event or of 
new information in relation with an already reported event 
 
Page 92 of 94

Page 93 of 94

Page 94 of 94