Non-interventional, Observational, Prospective, Multicentre Study in a Routine Clinical Care Setting Using a Marketed Medical Device in Line With the Corresponding IFU in the Intended Patient Population
Conditions: Esophagus Injury, Rectal Lesion
Sponsor: Lohmann & Rauscher

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Suprasorb® CNP endo used for negative pressure therapy in the oesophagus and 
rectum to support defect and wound healing 
Study Protocol 
Title 
Suprasorb® CNP endo used for negative pressure therapy in the 
oesophagus and rectum to support defect and wound healing 
Short title/ acronym 
Velox Study 
Protocol version identifier 
Version no. 1.0 dated 07.12.2023 
Study register number 
NCT05476263 
Type of study 
This PMCF study designed as non-interventional, observational, 
prospective, multicentre study in a routine clinical care setting using 
a marketed medical device in line with the corresponding IFU in the 
intended patient population. 
Country(ies) in the study 
Germany 
Most relevant regulatory stand-
ards to be followed 
ISO 14155:2020, EU MDR (as far as applicable), GDPR, Medizin-
produkte-Anwendermelde- und Informationsverordnung (MPAMIV) 
Legal Sponsor 
Lohmann 
& 
Rauscher 
GmbH 
& 
Co. 
KG 
Irlicherstr. 55, 56567 Neuwied, Germany 
CRO 
CRI 
– 
The 
Clinical 
Research 
Institute 
GmbH 
Arnulfstr. 19, 80335 Munich, Germany 
Medicinal product of interest 
Suprasorb® CNP endo 
Medicinal Product Marketing Au-
thorisation No. 
Suprasorb® 
CNP 
endo 
therapy 
unit 
Basic 
UDI-DI 
No. 
426058604EndoAspE2, dated 16.06.2021; CNP endo Foam Drain 
CE certificate No. G10 045286 0079 Rev 01, dated 03.08.2023; 
CNP endo Foam Drain N CE certificate No. G10 045286 0079 Rev 
01, dated 03.08.2023; CNP endo Overtube Basic UDI-DI No. 
4021447-0181-L4, dated 29.08.2023; CNP endo Proctoscope 
Basic UDI-DI No. 37016034AUP24A5, dated 10.11.2022; CNP 
endo Nasal Tube Basic UDI-DI No. 4021447-0180-KZ, dated 
29.08.2023; CNP endo Tube Clamp Basic UDI-DI No. 4021447-
0184-LD, dated 29.08.2023; CNP endo Y-Connector Basic UDI-DI 
No. 4021447-0185-LG, dated 29.08.2023; CNP endo Nasal Dress-
ing Basic UDI-DI No. 4260402642375H, dated 27.05.2021; CNP 
endo Rectal Fixation Dressing REF No. 90-30-14, dated 
27.05.2022; 
Marketing authorisation 
holder(s) 
Lohmann 
& 
Rauscher 
International 
GmbH 
& 
Co. 
KG 
Westerwaldstr. 4, 56579 Rengsdorf, Germany 
Author of protocol 
Thomas Fetsch, MD (CRI), Daria Trofimenko, MD (Lohmann & 
Rauscher) 

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All information in this study protocol including attachments provided to you as investigator, potential investiga-
tor, sub-investigator, committee member or other third party must be treated confidentially. The right to use 
this information is limited to you, your staff, members of the relevant committees or entitled authorities. The 
objectives and the content of this study, as well as its results, must be treated confidentially and may not be 
made available to third parties at any time before, during and after the study without written approval of the 
sponsor except to the extent necessary to get informed consent from patients. This applies to investigators 
and all supporting staff involved in the study. Transmission, duplication or use for publication is permitted only 
with the written agreement of the sponsor. 
 
 

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Table of contents 
Table of contents ................................................................................................................................ 3 
List of abbreviations ............................................................................................................................ 5 
1. 
General ....................................................................................................................................... 7 
1.1 
Steering Committee (SC) ................................................................................................... 7 
1.2 
Clinical Event Committee (CEC) ........................................................................................ 7 
1.3 
Overall synopsis of the clinical study .................................................................................. 8 
2. 
Identification and description of the investigational device(s) ...................................................... 11 
3. 
Justification for the design of the clinical study ........................................................................... 11 
3.1 
Medical and scientific background.................................................................................... 11 
3.2 
Rational ........................................................................................................................... 12 
4. 
Benefits and risks of investigational device, clinical procedures and clinical study ...................... 14 
4.1 
Anticipated clinical benefits of investigational devices ...................................................... 14 
4.2 
Anticipated adverse effects of investigational devices ...................................................... 15 
4.3 
Effects of study participation ............................................................................................ 15 
4.4 
Possible interactions with concomitant medical treatments ............................................... 16 
4.5 
Steps that will be taken to control or mitigate the risks ...................................................... 16 
4.6 
Rationale for benefit-risk ratio .......................................................................................... 16 
5. 
Objectives and hypotheses of the clinical study.......................................................................... 16 
5.1 
Purpose of the clinical study, claims for clinical performance, effectiveness or safety of the 
investigational device ....................................................................................................... 16 
5.2 
Objectives ....................................................................................................................... 17 
5.3 
Scientific justification and clinical relevance for effect sizes, non-inferiority margins or 
equivalence limits ............................................................................................................ 17 
5.4 
Risks and anticipated adverse device effects that are to be assessed .............................. 18 
6. 
Design of the clinical study ........................................................................................................ 18 
6.1 
General ........................................................................................................................... 18 
6.2 
Investigational device(s) and comparator(s) ..................................................................... 20 
6.3 
Subjects .......................................................................................................................... 21 
6.4 
Procedures ...................................................................................................................... 23 
6.5 
Monitoring plan ................................................................................................................ 26 
7. 
Statistical considerations ........................................................................................................... 26 
8. 
Data management ..................................................................................................................... 26 
8.1 
Electronic case reporting form.......................................................................................... 27 
8.2 
Personal data and data protection.................................................................................... 27 
8.3 
Completion of Case Report Forms ................................................................................... 27 
9. 
Amendments to the study protocol ............................................................................................. 28 
10. Deviations from study protocol ................................................................................................... 29 

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11. Device accountability ................................................................................................................. 29 
12. Statements of compliance.......................................................................................................... 29 
13. Informed consent process.......................................................................................................... 29 
14. Adverse events, adverse device effects and device deficiencies ................................................ 30 
14.1 Definitions ....................................................................................................................... 30 
14.2 Device Related Adverse Events ....................................................................................... 32 
14.3 Recording and reporting of reportable events ................................................................... 32 
15. Vulnerable population ................................................................................................................ 35 
16. Suspension or premature termination of the study ..................................................................... 35 
17. Publication policy ....................................................................................................................... 35 
18. Bibliography .............................................................................................................................. 36 
 
 
 

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List of abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AEoSI 
Adverse Event of Special Interest 
CAL 
Colorectal Anastomotic Leakage 
CEC 
Clinical Event Committee 
CFR 11 
Code of Federal Regulations Part 11 (USA) 
CDISC 
Clinical Data Interchange Standards Consortium 
CRO  
Contract Research Organisation 
CTMS 
Clinical Trial Management System 
e-CRF  
Electronic Case Report Form  
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
EVAC 
Endoscopic Vacuum-Assisted Closure 
EVT 
Endoscopic / Endoluminal Vacuum Therapy 
FPI 
First Patient In 
FU 
Follow-up 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
ICH-GCP 
International Conference on Harmonisation on Good Clinical Practice 
ICU 
Intensive Care Unit 
IFU 
Approved Instruction For Use of a medical device according to CE certification 
ITT 
Intention-To-Treat 
LOS 
Length of stay 
LPI 
Last Patient In 
LPO 
Last Patient Out 
MDR 
EU Medical Device Regulation 2017/745 
OTSC 
Over-The-Scope-Clip 
PMCF 
Post-Market Clinical Follow-up as defined in EU MDR, especially Annex XIV 
PRRC-V 
Person Responsible for Regulatory Compliance-Vigilance 
PSS 
Perforation Severity Score  
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SC 
Steering Committee 
SEMS 
Self-Expanding Metal Stent 
SEPS 
Self-Expanding Plastic Stent 
SOP 
Standard Operating Procedure 
 
 
 

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Signatures 
The undersigned have read this protocol and agreed to conduct this study in accordance with all stipulations 
of the protocol and in accordance with applicable regulations. 
 
Date 
Signature 
 
___________________ 
_____________________________________ 
 
Dr Maria Burian, SC member 
 
 
___________________ 
_____________________________________ 
 
Dr Marcus Kantowski, SC member 
 
___________________ 
_____________________________________ 
 
Dr Konstantinos Kouladouros, SC member 
 
 
___________________ 
_____________________________________ 
 
Prof Dr Mike Laukötter, Chair of SC 
 
 
___________________ 
_____________________________________ 
 
Dr Gunnar Loske, SC member 
 
 
___________________ 
_____________________________________ 
 
Prof Dr Anja Schaible, SC member 
 
 
___________________ 
_____________________________________ 
 
Dr Christine Stier, SC member 
 
 
___________________ 
_____________________________________ 
 
Dr Martin Abel, Sponsor representative 
 
 
 
 
___________________ 
_____________________________________ 
 
Signature of principal investigator of study site 
 
 
______________________________________________ 
 
Name of principal investigator of study site 
 
 

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1. 
General 
This study protocol reflects the topics defined in annex A (clinical investigation plan) of ISO 14155:2020. Topics 
1.1 to 1.3 are represented on the cover page, thus, numbering starts with topic 1.4 of annex A as 1.1 of this 
study protocol. Some headlines of annex A have been modified to better represent the needs of this non-
interventional, observational study, e.g. 1.4 (here 1.1) which is renamed to “Steering Committee”. A list of 
principal investigators, investigation sites, and institutions according to 1.4 of annex A is given in a stand-alone 
document referred to in Annex 1 of this study protocol. 
Throughout this study protocol the term “study” is used as umbrella term for any systematic clinical investiga-
tion involving one or more human subjects (e.g. observational clinical investigations) whereas “trial” means 
any study which is interventional (e.g. by means of randomisation) and “investigation” is being used as regu-
latory term for any study undertaken to assess the safety or performance of a dedicated investigational product. 
Consequently, the term “study” will also be used in compound words in the sense described above, e.g. “study 
site” instead of “investigation site” or “study protocol” instead of “investigation plan”. 
1.1 
Steering Committee (SC) 
An independent SC is responsible for scientific and medical advice of the sponsor including continuous over-
view of the study to assure reliability of data collected and analysed within this non-interventional, observational 
study. A corresponding charter defines duties and responsibilities of the SC. A list of SC members is provided 
in a separate document. 
1.2 
Clinical Event Committee (CEC) 
The CEC will centrally adjudicate serious adverse events (SAEs) and adverse events (AEs) of special interest 
based on coded (pseudonymized) copies of corresponding medical files to assess if it fulfils criteria for defect 
treatment complication or being related to defect treatment. In addition, because hospitalisation decisions 
might be subject to local practices, social considerations, bed availability, and so on, all hospitalisations will be 
reviewed to assess the reason and appropriateness of each hospitalisation, i.e. whether it is “for therapy of 
index defect”. 
A corresponding charter defines duties and responsibilities of the CEC. A list of CEC members is provided in 
a separate document. 
 
 

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1.3 
Overall synopsis of the clinical study 
 
TITLE 
Suprasorb® CNP endo used for negative pressure therapy in the oesopha-
gus and rectum to support defect and wound healing  
CHIEF INVESTIGATOR 
Prof. Dr. med. Mike Laukötter, Rheine 
ACRONYM 
Velox Study 
SPONSOR 
Lohmann & Rauscher GmbH & Co. KG 
Irlicherstr. 55, 56567 Neuwied, Germany 
BACKGROUND AND  
RATIONALE 
Anastomotic insufficiencies and oesophageal perforations are life-threaten-
ing, severe complications of the upper gastrointestinal (GI) surgery. The re-
ported incidence of anastomotic leaks overall is between 5% and 25%. De-
pending on the position and dimensions of the leaks, they are associated with 
a mortality of up to 60% [28]. Therapy of patients who experience sympto-
matic intrathoracic anastomotic leaks is usually difficult and carries a high risk 
of severe secondary complications. Depending on the severity of the anasto-
motic leakage, the time interval after primary surgery, the general condition 
of the patient and the anastomotic location, several treatment strategies are 
available, such as conservative, endoscopic or surgical treatment. Conserva-
tive treatment approach includes strict nil per oral, drainage and i.v. antibiot-
ics. Surgical treatment options span from the re-execution of the anastomosis 
with augmentation of the anastomotic area by vital tissue (e.g. muscle flap, 
omental flap), to complete surgical deviation by taking down the oesophageal 
conduit and creation of a cervical stoma. Endoscopic methods include injec-
tion of fibrin glue and clip administration, introduction of self-expanding metal 
or plastic stents and endoluminal vacuum therapy. 
Colorectal anastomotic leakage (CAL) also remains a frequent and danger-
ous complication after gastrointestinal surgery, occurring in 4-33% of patients 
and contributing to one third of postoperative mortality. An anastomotic defect 
causes leakage of colonic content into the abdominal or pelvic cavity, leading 
to peritonitis, abscess formation or sepsis. CAL substantially (by 1-2 weeks) 
prolongs hospital stay and increases medical costs by as much as 
US$24,000 within the first period of hospitalisation, thereby approximately 
tripling the expenditure in comparison to that of a normal recovery. Moreover, 
CAL is identified as a risk factor for local recurrence of colorectal cancer and 
is reported to reduce long-term cancer specific survival. 
The type of intervention strongly depends on the severity of CAL, which is 
hard to determine, and therefore the choice of intervention for a suspicious 
leakage is quite complex with very limited evidence-based strategy available 
at present. Colorectal surgeons use various methods, i.a. conservative fol-
low-up, adhesive materials (e.g. cyanoacrylate), abscess drainage, open pel-
vic lavage, construction of an entirely new anastomosis, and endoscopic or 
surgical interventions, such as diverting or ending the stoma and transanas-
tomotic continuous drainage system with negative pressure. 
Though a number of studies and case reports have demonstrated promising 
results regarding efficacy of EVT in treatment of both upper and lower GI tract 

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perforations and anastomotic insufficiencies, and, potentially, even better 
safety profile of this treatment in comparison with other conventional treat-
ment methods, the amount of data is still relatively small and additional data 
collection and analysis is necessary. 
STUDY OBJECTIVE(S) 
To assess in a routine clinical care setting the performance of Suprasorb® 
CNP endo regarding wound healing in patients with oesophagus and rectum 
defects of different aetiologies. 
STUDY DESIGN 
This PMCF study designed as non-interventional, observational, prospective, 
multicentre study in a routine clinical care setting using a marketed medical 
device in line with the corresponding IFU in the intended patient population.  
STUDY POPULATION 
Medical condition/ 
main selection criteria 
Inclusion criteria: 
I1. ≥ 18 years of age 
I2. Acute transmural defects, injuries and wounds in oesophagus or rec-
tum, including perforations (iatrogenic or spontaneous) and anastomotic 
insufficiencies (Index defect) 
I3. Indication of treatment with Suprasorb® CNP endo system according to 
IFU and medical guidelines 
I4. Signed informed consent for usage of data 
Exclusion criteria: 
E1. Pre-existing coagulation disorders with increased risk of bleeding 
E2. Defects involving the bronchial system (bronchus/trachea/pulmo) 
E3. Any foreseeable deviation from IFU of Suprasorb® CNP endo 
E4. Known intolerance or allergy to one or more components of Suprasorb® 
CNP endo 
Number of subjects 
About 110 adult female and male patients with acute defects, injuries and 
wounds in the oesophagus or rectum and an indication of treatment with 
Suprasorb® CNP endo system according to IFU and medical guidelines. 
Expected number of sites 
and countries 
About 10 study sites in Germany, which are trained for the use of Supra-
sorb® CNP endo system treatment in routine clinical care, will screen eligi-
ble patients. 
INVESTIGATIONAL  
INTERVENTIONS 
The study protocol does not define specific study procedures for patients en-
rolled. Therapies and procedures during the course of this study will be per-
formed according to the decision of the treating physician based on current 
applicable medical guidelines and on local policy in clinical routine care. This 
includes the prescription and the use of the device of interest and possible 
measures at enrolment and in follow-up. All devices will be used according 
to the corresponding IFU, only. The only study-specific obligation within this 
observational study is to document pre-defined medical and procedural data 
if available in routine clinical care in the electronic CRF (eCRF) at a level of 
data quality following international standards on clinical studies. 

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OUTCOME  
PARAMETERS 
Primary endpoint 
Time period in days from index use of Suprasorb® CNP endo to release for 
oral food intake (in upper GI tract use) or endoscopic release for stoma relo-
cation (in lower GI tract use). 
Secondary endpoints 
1. 
Number of SAEs related to defect treatment within total observation pe-
riod. 
2. 
Number of nights in hospital for therapy of index defect. 
3. 
Number of nights at the ICU during hospital stay for therapy of index 
defect. 
 
ASSESSMENT  
SCHEDULEs 
 
Screening and baseline/enrolment visit (day 1). 
 
Treatment of the index defect 
 
Follow-up (FU) visits  
STATISTICAL  
CONSIDERATIONS 
In this observational study the time period from index therapy to release for 
oral food intake (in upper GI tract use) or endoscopic release for stoma relo-
cation (in lower GI tract use) will be compared to published historic controls. 
For this, the time period is compared to published data of other EVAC and 
conventionally managed therapy, especially data from Wasmann et al. [29]. 
In addition, after half of the patients with complete follow-up, an interim anal-
ysis will be performed and sample size will be recalculated. It is expected that 
until then the results of a randomized clinical trial comparing an EVAC ther-
apy to standard minimally invasive oesophagectomy (refer to NCT04162860 
and [22]) will be available for adaptation of assumed confidence intervals and 
sample size (see 6.3.7). The hypothesis of superiority against conventionally 
managed therapy will be tested confirmatory. 
Data from all study sites will be pooled for analysis. Standard statistical meth-
ods will be used to analyse all data. Continuous variables will be summarized 
using the number of observations, mean, median, standard deviation, mini-
mum and maximum values. Categorical variables will be summarized using 
the number of observations and percentages. 
DURATION OF STUDY 
PERIODS 
Total study duration: 
 
Enrolment period: about 24 months. 
 
Follow-up period of last patient enrolled: about 3 months. 
 
Total study period: about 27 months. 
Individual study duration: 
 
Expected median follow-up period: about 3 months per patient. 
 
 

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2. 
Identification and description of the investigational device(s) 
This is a non-interventional, purely observational study using only marketed medical devices in line with the 
approved Instruction For Use (IFU) in the intended patient population. The investigational device is Suprasorb® 
CNP endo, used for EVAC, an endoscopic vacuum assisted therapy or endoluminal negative pressure wound 
therapy, assessed as class IIb (EU Quality Management System Certificate (MDR) G10 045286 0079 Rev.01) 
and class I medical devices (please refer to Medicinal Product Marketing Authorisation No.) 
The Suprasorb® CNP endo therapy unit is used in combination with Suprasorb® CNP endo Kits to create, 
maintain, and control negative pressure and to drain body fluids in the upper and lower GI tract. EVAC can be 
used as intraluminal or intracavitary treatment of defects of the upper and lower GI tract. Negative pressure 
wound therapy drainage properties are achieved by a connection to the therapy unit with exudate canister 
which continuously removes secretions from wounds. The devices are available as disposable accessories for 
the use with the Suprasorb® CNP endo therapy unit in 4 different Kitpacks: Suprasorb® CNP endo Kit Oral, 
Suprasorb® CNP endo Kit Oral N, Suprasorb® CNP endo Kit Rectal and Suprasorb® CNP endo Kit AddOn. A 
detailed description is provided in the approved IFU. 
The investigational devices will be used in routine clinical care based on the decision of the treating physician 
in line with IFU, medical guidelines and local policy.  
3. 
Justification for the design of the clinical study 
3.1 
Medical and scientific background 
Anastomotic insufficiencies and oesophageal perforations are life-threatening, severe complications of the up-
per gastrointestinal (GI) surgery. The reported incidence of anastomotic leaks overall is between 5% and 25%. 
Depending on the position and dimensions of the leaks, they are associated with a mortality of up to 60% [28]. 
Therapy of patients who experience symptomatic intrathoracic anastomotic leaks is usually difficult and carries 
a high risk of severe secondary complications. Depending on the severity of the anastomotic leakage, the time 
interval after primary surgery, the general condition of the patient and the anastomotic location, several treat-
ment strategies are available, such as conservative, endoscopic or surgical treatment. Conservative treatment 
approach includes strict nil per oral, drainage and i.v. antibiotics. Surgical treatment options span from the re-
execution of the anastomosis with augmentation of the anastomotic area by vital tissue (e.g. muscle flap, 
omental flap), to complete surgical deviation by taking down the oesophageal conduit and creation of a cervical 
stoma. Endoscopic methods include injection of fibrin glue and clip administration, introduction of self-expand-
ing metal or plastic stents and endoluminal vacuum therapy. 
As one can see already from the number of possible options, no general treatment of choice or standardized 
treatment algorithm exists so far. Each method has its pros and contras. While some surgeons recommend 
aggressive surgery, others prefer conservative approaches, including peri-anastomotic drainage, total paren-
teral nutrition, nasogastric decompression, and use of broad-spectrum antibiotics. Also, although introduction 
of self-expanding metallic coated stents was regarded as a considerable advancement in treatment of thoracic 
anastomotic leaks, their usage does not always lead to a sufficient sealing of the leakage, and dislocation rates 
up to 30% have been reported [27]. Another limiting factor for the stent placement may be a need for additional 
surgical interventions to provide drainage and removal of the septic focus [25, 27, 31]. 
Colorectal anastomotic leakage (CAL) also remains a frequent and dangerous complication after gastrointes-
tinal surgery, occurring in 4-33% of patients and contributing to one third of postoperative mortality. An anas-
tomotic defect causes leakage of colonic content into the abdominal or pelvic cavity, leading to peritonitis, 
abscess formation or sepsis. CAL substantially (by 1-2 weeks) prolongs hospital stay and increases medical 
costs by as much as US$24,000 within the first period of hospitalisation, thereby approximately tripling the 
expenditure in comparison to that of a normal recovery. Moreover, CAL is identified as a risk factor for local 
recurrence of colorectal cancer and is reported to reduce long-term cancer specific survival. 

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The type of intervention strongly depends on the severity of CAL, which is hard to determine, and therefore 
the choice of intervention for a suspicious leakage is quite complex with very limited evidence-based strategy 
available at present. Colorectal surgeons use various methods, i.a. conservative follow-up, adhesive materials 
(e.g. cyanoacrylate), abscess drainage, open pelvic lavage, construction of an entirely new anastomosis, and 
endoscopic or surgical interventions, such as diverting or ending the stoma and transanastomotic continuous 
drainage system with negative pressure. 
3.2 
Rationale 
Endoscopic (endoluminal) vacuum therapy (EVT), alternative term endoscopic vacuum-assisted closure 
(EVAC), was for the first time applied in Europe by Weidenhagen et al. [31] in 2003 for use in the rectum and 
in 2007 by Loske et al. [12] for use in the foregut. 
Loske et al. [13] summarized the experience of EVT for patients with anastomotic insufficiency secondary to 
esophagectomy or gastrectomy (n=5), iatrogenic oesophageal perforation (n=2), oesophageal wall necrosis 
(n = 1), Boerhaave’s syndrome (n=1), and perforation of oesophageal cancer (n=1). After one to seven 
changes of the sponge at intervals of 2–7 days and a mean therapy duration of 12 days, the defects were 
healed in all the surviving patients (n=9). One patient died of intercurrent severe colitis. In three cases, a 
revision laparotomy was necessary at the beginning of treatment. No post-interventional stricture or functional 
relevant scar formation was observed during a follow-up period of 10 – 380 days after termination of the vac-
uum therapy. 
In a pilot study of EVT in the upper GI tract, conducted by Ahrens et al. [1], four patients with thoracoabdominal 
oesophagus resection and one patient with myotomy of Zenker's diverticulum were successfully treated till 
closure of their leakages without a need for surgical re-intervention. Two patients required endoscopic dilation 
of moderate anastomotic stenosis after completion of EVT. 
Wedemeyer et al. [30] could demonstrate successful use of EVT in the management of major postsurgical 
gastrooesophageal intrathoracic leaks (prospective single-centre study with 8 patients). Leakage closure by 
EVT was achieved in 7 cases, EVT could not be completed in one case due to safety concerns. No SAEs 
associated with the endoscopic intervention or EVT were noted. Complications observed: patients reported 
discomfort in the nose and throat (n=8), sponge dislocation (n=2). 
In the retrospective analysis by Brangewitz et al. [6], comparing EVT versus stent management (self-expanding 
metal (SEMS) or plastic stents (SEPS)), data of 39 patients who were treated with SEMS or SEPS and 32 
patients who were treated with EVT for intrathoracic leakage were analysed. Successful wound closure was 
independently associated with EVT (hazard ratio 2.997, 95% confidence interval [95%CI] 1.568–5.729; 
P=0.001). The overall closure rate was significantly higher in the EVT group (84.4%) compared with the 
SEMS/SEPS group (53.8%). No difference was found for hospitalisation and hospital mortality. Significantly 
more strictures were observed in the stent group (28.2% vs. 9.4% with EVT, P<0.05). Complications in the 
stent group constituted: stent dislocation (n=6), anastomotic stricture (n=11), severe bleed at the upper end of 
the stent followed by immediate surgical revision (n=1), oesophageal necrosis with fatal outcome (n=1), self-
limiting bleeding after stent-removal (n=2), ulcers after stent removal, not requiring specific therapy (n=5). 
Complications in the EVT group constituted: sponge dislocation (n=5), bleeding after sponge removal (n=1), 
significant mucosal tear proximal to the anastomosis during sponge removal (n=1), bronchooesophageal fis-
tula with later required surgery (n=1), anastomotic stricture (n=3). 
Heits et al. [8] analysed data of 10 patients, treated by EVT for oesophageal perforations, located in the cervical 
(n=3) and thoracic (n=7) oesophagus. Complete healing of the wound was achieved in 9 cases. One patient 
has died (failure of the cardiovascular system caused by a known heart insufficiency). EVT-associated com-
plications (mediastinal emphysema) occurred in 7 patients.  
Bludau et al. [4] summarized the experience of EVT for patients with oesophageal leakages (n=14). For 6 of 
14 patients, EVT was combined with a placement of self-expanding metal stents. Complete closure of the 

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oesophageal defect was achieved in 12 cases. Two patients died due to prolonged sepsis before EVT could 
be completed. In two cases, oesophageal stenosis was diagnosed, which was treated successfully by one-
time pneumatic dilation. No other complications related to the EVT were observed. 
Strangio et al. [26] evaluated performance and safety of EVT in 25 patients with partial colonic anastomotic 
leakage. Complete healing was achieved in 22 cases. Three patients developed a major complication (1 ure-
teric fistula, 1 ileal fistula, and 1 pararectal abscess), all successfully treated by surgery. Ileostomy closure was 
achieved in 11 patients. No mortality related to the procedure was observed. 
In a retrospective study including 15 patients with pelvic anastomotic leakage after colorectal surgery [9], lumen 
integrity was achieved in 12 cases. Treatment was discontinued due to progression of pelvic sepsis in two 
patients and due to bleeding in one patient. No complications, related to the EVT, were reported. 
In a study of EVT by upper gastrointestinal leaks and perforations, conducted by Smallwood et al. [25], com-
plete closure of perforation or leak after an average of 35.8 days of EVT was demonstrated for all patients 
(n=6). No deaths occurred within 30 days following EVT. One patient died following complete closure of his 
perforation and transfer to an acute care facility due to an unrelated complication. There were no complications 
directly related to the use of EVT. 
Mennigen et al. [20] compared 30 patients, treated with stent insertion, with 15 patients, treated with EVT for 
management of oesophageal anastomotic leakage following oesophagectomy, performed with a stapled in-
trathoracic anastomosis (end-to-side, circular stapler). The rate of endoscopic anastomotic healing was found 
to be higher for endoscopic vacuum therapy (93.3%, vs. 63.3% in a stent group; P=0.038). No significant 
difference was observed for overall mortality, duration of therapy, and length of hospitalisation. 
In a prospective cohort study [11] including 52 patients with oesophageal anastomotic insufficiencies of differ-
ent origin, healing of the oesophageal wall defects in 49 cases was observed (in 7 cases, final closure was 
performed by additional clipping of residual superficial defects with an Over-The-Scope-Clip [OTSC]). One 
patient showed no response to EVT and two patients died due to haemorrhage related to the procedure. Post-
interventional stricture was observed during follow up period in 4 patients. 
In a retrospective review of case series [3], endoscopic vacuum therapy was applied in 14 patients with colo-
rectal leak. Overall success rate was 79%, favored by early beginning of treatment. Median duration of treat-
ment was 12.5 sessions (range 4 – 40). Median time for complete healing was 40.5 days (range 8 – 114). No 
EVT-related complications were observed.  
The effectiveness and safety of EVAC therapy was verified in a study including 55 patients with anastomotic 
leakage in the upper GI tract [32]. Patients underwent elective oesophageal resection and EVAC (intracavitary 
or intraluminally) was initiated. Sponge changes were performed either every 3 days for intracavitary localiza-
tion or every 5 – 7 days for intraluminal position. Successful closure was achieved in 49 patients (n=49) while 
complication rate was 5.4 % (n=3). One patient suffered from bleeding while 2 patients had minor sedation-
related complications. Median number of EVAC procedures was 3 with median 14-day duration of therapy. 
Mortality rate was 7.2 % (n=4); 3 patients died despite of complete healing due to multiple organ failure, acute 
respiratory distress syndrome and urosepsis. 
In the prospective, observational, national, multicenter registry of Eso-Sponge® for anastomotic leakage after 
esophageal resection or perforation (23) a success rate of 91 % was demonstrated. 
In 2019, Loske (18) summarized the data from 18 studies (420 patients worldwide) in which more than five pa-
tients were treated with endoscopic negative pressure therapy in the upper gastrointestinal tract, and the suc-
cess rate was found to be 87% (range 60-100%). 
A systematic search of MEDLINE/PubMed and Cochrane databases (10) was performed by Kühn et al. using 
search terms related to EVT and colorectal defects (anastomotic leakage, rectal stump insufficiency) according 
to the PRISMA guidelines. Randomized controlled trials (RCTs), observational studies, and case series pub-
lished by December 2020 were eligible for inclusion. A meta-analysis was conducted on the success of EVT, 
stoma reversal rate after EVT as well as procedure-related complications. Twenty-four studies reporting on 

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690 patients with colorectal defects undergoing EVT were included. The mean rate of success was 81.4% 
(95% CI: 74.0%-87.1%). The proportion of diverted patients was 76.4% (95% CI: 64.9%-85.0%). The mean 
rate of ostomy reversal across the studies was 66.7% (95% CI: 58.0%-74.4%). Sixty-four patients were re-
ported with EVT-associated complications, the weighted mean complication rate across the studies was 12.1% 
(95% CI: 9.7%-15.2%). 
Also, numerous case reports and case series describe the successful usage of EVT for closure of oesophageal 
[7, 14, 15, 16, 17, 21, 30] and rectal [2, 5] defects. 
Only limited evidence for comparison of different treatment approaches for both upper and lower GI tract de-
fects can be found in literature. To compare EVT of leakage after oesophagectomy with other therapy regimes, 
Schniewind et al. [24] analysed 62 patients, who have developed an anastomotic leak. Therapy options in-
cluded surgical revision (n=18), endoluminal vacuum therapy (n = 17), endoscopic stent application (n=12), 
and conservative management (n=15). In-hospital mortality constituted 26% (of which EVT 12% [n=2], surgery 
50% [n=9], stent 42% [n=5], 0% of the conservatively treated patients). The survival in the EVT group was 
significantly superior to that of the surgically treated patients (p = 0.011, log rank test) and to that of the stented 
patients with oesophageal leakage (p =0.00014, log rank test). To summarize, this study suggests that EVT is 
an effective procedure for a management of major leakage from oesophageal anastomoses and might be 
superior to surgical revision and stent placement, especially in septic patients. However, it is obvious that this 
data should be further confirmed on bigger patient population. 
In the study by Mees et al. [19] comparing patients treated with EVT (n=5: rectal carcinoma n=3, ulcerative 
colitis n=2) vs. transrectal lavage (n=5: rectal carcinoma n=3, ulcerative colitis n=2) after colorectal resection, 
median time of defect closure constituted 45 days in the EVT group, compared to 101 days in the lavage group. 
Average time in the hospital constituted 37 and 45 days, respectively. EVT was well tolerated by all patients 
and no specific side effects during or after the therapy were observed. One patient in the EVT group developed 
a mild rectal stenosis in the anastomotic area during the follow-up. This stenosis was treated by self-dilatation 
using Hegar's dilator for 4 weeks. Overall costs were summarized for both procedures considering the differ-
ences in the number of sessions (EVT - 7 replacements/ patient; lavage - 12 procedures/ patient), costs for 
staff and material. This resulted in comparable costs of 122.85 € (EVT) vs. 119.4 € (lavage), respectively. 
Though a number of studies and case reports have demonstrated promising results regarding efficacy of EVT 
in treatment of both upper and lower GI tract perforations and anastomotic insufficiencies, and, potentially, 
even better safety profile of this treatment in comparison with other conventional treatment methods, the 
amount of data is still relatively small and additional data collection and analysis is necessary. 
4. 
Benefits and risks of investigational device, clinical procedures and clinical study 
All medical devices used in this study are CE-marked, marketed devices which will only be used in line with 
the approved IFU in the intended patient population. 
4.1 
Anticipated clinical benefits of investigational devices 
Patients requiring EVAC are considered to be in a life-threatening condition due to the possibility of developing 
mediastinitis, peritonitis as well as consecutive sepsis with fatal outcome. With regard to the benefits of Supra-
sorb® CNP endo, review of current literature allows the conclusion that safety and tolerability of the IP are 
acceptable. Therefore, the IP can be considered suitable for the management of endoluminal wounds including 
perforations and anastomotic leakages. There is sufficient clinical evidence to declare conformity of the device 
with the general safety and performance requirements. 

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4.2 
Anticipated adverse effects of investigational devices 
4.2.1 Side effects 
The biocompatibility of Suprasorb® CNP endo can be classified as acceptable for the intended purpose and 
application. Suprasorb® CNP endo is made of materials which have been well-characterised chemically and 
physically in the published literature. Overall, the combination of non-clinical and clinical data on Suprasorb® 
CNP endo demonstrates that Suprasorb® CNP endo devices are suitable for their intended purpose and con-
firms that the clinical benefits of the device outweigh theoretical and known risks.  
The most common complications recorded for the devices are, e.g. pain, nasal bleeding and mediastinal em-
physema. However, the devices showed to be feasible and well-tolerated device for EVAC. It should be kept 
in mind that patients requiring EVAC are considered to be in a life-threatening condition due to the possibility 
of developing mediastinitis, peritonitis as well as consecutive sepsis with fatal outcome. 
4.2.2 Interactions 
None known. 
4.3 
Effects of study participation 
4.3.1 Anticipated risks of study participation 
Participation does not pose additional risks compared to routine clinical care because there are no study inter-
ventions in this purely observational clinical study. Participation just means following routine clinical care deci-
sions and procedures but allowing to use available medical data in a central study database. 
 
All medical devices used in this study are marketed products used in clinical routine care in line with market 
authorisation and represent standard of care in this therapeutic indication. This also applies to all medical 
procedures within the study. 
 
This clinical study is purely observational. The study protocol does not define any study-specific interven-
tion or procedure to be performed. The only study-specific obligation within this observational study is to 
document pre-defined medical and procedural data if available in routine clinical care at a level of data 
quality following international standards on clinical studies. 
 
All therapeutic decisions and procedures are performed as routine clinical care following all applicable 
ethical and regulatory standards. Therefore, adverse events will occur in clinical manifestations and at 
rates as in routine clinical care. 
 
The study will be conducted in accordance with the principles laid down in the Declaration of Helsinki in its 
version of October 2013 (Fortaleza) and in accordance with ISO 14155:2020. 
 
Before initiating the study in a country, approval of the corresponding Ethics Committees (ECs) will be 
obtained. 
4.3.2 Anticipated benefits of study participation 
No to minor additional benefit will be added for patients participating in this purely observational clinical study. 
 
All therapeutic decisions and procedures are following individual decisions of the treating physician and 
are performed as routine clinical care. Thus, no additional benefit compared to routine clinical care will 
occur because all procedures are routine clinical care. 

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 
Little additional benefit might occur based on standardised data documentation and queries related to data 
entries provided by a third party (e. g. a contract research organisation) which both might lead to more 
standardised routine clinical care procedures and decisions. 
4.4 
Possible interactions with concomitant medical treatments 
None known. 
4.5 
Steps that will be taken to control or mitigate the risks 
All therapeutic decisions and procedures are following individual decisions of the treating physician and are 
performed as routine clinical care practice following applicable medical standards. All relevant safety infor-
mation concerning residual risks is provided to the user in the product labelling and instructions for use. This 
comprises contraindications, side effects, warnings and precautions. 
The study protocol does not define any study-specific intervention or procedure to be performed. Therefore, 
adverse events representing the potential risks are expected to occur in clinical manifestations and at rates as 
in routine clinical care. The investigator will promptly report to the sponsor serious adverse events and adverse 
device effects according to 14.3. The sponsor will, based on these data, perform actions in case of hazards 
and foreseeable damage to patients and report promptly to regulatory bodies according to 14.3. 
4.6 
Rationale for benefit-risk ratio 
The study is purely observational with documentation of routine clinical care procedures and outcomes, without 
adding any study specific interventions or procedures. Thus, the structural risk of the study defines as low, i.e. 
not exceeding the risk of use of Suprasorb® CNP endo in routine clinical care. 
From Clinical Evaluation Report (DI_CER_00020_02, Feb 2022) and risk management perspective it can be 
concluded that the benefit / risk ratio for Suprasorb® CNP endo is positive. 
5. 
Objectives and hypotheses of the clinical study 
5.1 
Purpose of the clinical study, claims for clinical performance, effectiveness or safety of the in-
vestigational device 
5.1.1 Purpose 
The study is performed as observational PMCF study to generate in the setting of routine clinical care reliable 
data on the therapeutic approach of Suprasorb® CNP endo used in adult patients for negative pressure therapy 
in the oesophagus and rectum to support defect and wound healing. It will comply with the requirements set 
out by the clinical data requirements of EU MDR 2017/745. 
5.1.2 Claims for clinical performance and effectiveness 
The Suprasorb® CNP endo claims to support defect and wound healing in the upper and lower gastrointestinal 
tract by draining body fluids and simultaneously provide the possibility of enteral feeding for the upper gastro-
intestinal tract. Defects like perforations (iatrogenic perforations, spontaneous perforations), anastomoses and 
anastomotic insufficiencies can be treated intraluminal and/or intracavity with Suprasorb® CNP endo. 
 

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5.1.3 Claims for clinical safety 
There is sufficient clinical data to declare conformity of the IP with the general safety and performance require-
ments with a positive benefit / risk ratio. 
5.2 
Objectives 
The objectives of this PMCF study are to confirm performance and safety of Suprasorb® CNP endo in routine 
clinical care by evaluation of clinical data after market approval, including detection of potential unexpected 
adverse events associated with its use within the certified indications and under the conditions of routine clin-
ical care. This will be assessed in defects of different aetiology in the oesophagus and rectum, thus, widely 
representing routine clinical care population and use. 
5.2.1 Primary objective 
To assess in a routine clinical care setting the performance of Suprasorb® CNP endo regarding wound healing 
in patients with oesophagus and rectum defects of different aetiologies. 
Wound healing is defined as release for oral food intake (in upper GI tract use) or endoscopic release for stoma 
relocation (in lower GI tract use).  
Time to wound healing is consequently defined as time from index use of Suprasorb® CNP endo to date of 
release for oral food intake (in upper GI tract use) or endoscopic release for stoma relocation (in lower GI tract 
use). 
5.2.2 Secondary objectives 
To assess in a routine clinical care setting in this patient population 
1. 
adequate safety of the use of Suprasorb® CNP endo, and 
2. 
duration of hospital care with use of Suprasorb® CNP endo. 
5.2.3 Hypotheses to be accepted or rejected by statistical data from the study 
The primary hypothesis is that the time period from index therapy to release for oral food intake (in upper GI 
tract use) or endoscopic release for stoma relocation (in lower GI tract use) will be superior to historic controls 
from literature reporting standard management of therapy without use of EVAC therapies. 
A Statistical Analysis Plan (SAP) will be prepared prior to start of data analysis detailing the statistical analysis 
methods which will be used. 
5.3 
Scientific justification and clinical relevance for effect sizes, non-inferiority margins or equiva-
lence limits 
This observational study will provide information on “real world” use and practice in treatment of both upper 
and lower GI tract perforations and anastomotic insufficiencies using the Suprasorb® CNP endo system in a 
routine clinical care setting. 
The indication for this treatment is decided in acute clinical situations needing urgent treatment, thus, a con-
trolled clinical trial setting will be impractical and may lead to a larger selection bias compared to a study which 
reports observation of routine clinical care without pre-defined study procedures and interventions. 
The study will only be performed in study sites which are trained for the use of the Suprasorb® CNP endo 
system treatment in routine clinical care and generally experienced in use of EVT for treatment of upper or 

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lower GI tract perforations and anastomotic insufficiencies. Thus, comparability in selection of patients, deci-
sion on indication and procedures performed can be presumed. 
5.4 
Risks and anticipated adverse device effects that are to be assessed 
The investigational device is a marketed, CE-certified product, which will be used within its intendent purpose. 
Rate of defect treatment complications (during index defect treatment and in follow-up treatments) and rate of 
SAEs related to defect treatment will be assessed. The term “defect treatment related” represents not only 
device-related but in total procedure-related AEs of special interest and SAEs. Non-serious AEs which are not 
classified as “of special interest” will not be assessed. 
6. 
Design of the clinical study 
6.1 
General 
6.1.1 Study design 
This PMCF study designed as non-interventional, observational, prospective, multicentre study in a routine 
clinical care setting using a marketed medical device in line with the corresponding IFU in the intended patient 
population. 
The routine clinical care of study patients is in no way influenced by their participation in this study. All clinical 
procedures and therapies are based on individual decisions of the treating physician following current applica-
ble medical guidelines and local policy, not pre-defined in the study protocol. Thus, this clinical study is purely 
observational. 
Patients will be screened at study sites, which have expertise in treatment of oesophageal and / or intestinal 
defects and are trained for the use of Suprasorb® CNP endo treatment.  
Patients will be enrolled in this non-interventional study if an indication for Suprasorb® CNP endo treatment 
was defined by the treating physician based on routine clinical care decisions, all inclusion and no exclusion 
criteria are met and written consent is given to use and process their routine clinical data according to data 
privacy standards.  
In most cases, enrolment into the study will take place after Suprasorb® CNP endo treatment related to the 
fact that the treatment decision for such patients is often made in a medically acute situation. A screening form 
will be used by the study site staff to document some anonymised data of all potentially eligible patients to-
gether with a reason if not participating in the study to control selection bias and to maintain prospective data 
generation. 
Patients will be diagnosed and evaluated for eligibility in routine clinical care by expert centres in the indication 
of interest and enrolled competitively by all authorised study sites without pre-defined quota for individual study 
sites. 
The study protocol does not define specific study procedures for patients enrolled. Therapies and procedures 
during the course of this study will be performed according to the decision of the treating physician based on 
current applicable medical guidelines and on local policy in clinical routine care. This includes the prescription 
and the use of the device of interest and possible measures at enrolment and in follow-up. All devices will be 
used according to the corresponding IFU, only. The only study-specific obligation within this observational 
study is to document pre-defined medical and procedural data if available in routine clinical care in the elec-
tronic CRF (eCRF) at a level of data quality following international standards on clinical studies. 
 
 

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Flowchart 
 
6.1.2 Measures to minimize or avoid bias 
The study site will document all consecutive patients, for whom treatment of acute oesophageal or intestinal 
defects using Suprasorb® CNP endo treatment is clinically indicated. If a potentially eligible patient refuses to 
consent participation in the study or other reasons for non-participation are existing, the patients’ minimum of 
medical data (age, sex, indication for treatment of interest) will be documented in a Screening Log located at 
the study site for potential review e.g. by clinical monitors of the CRO to check for potential selection bias. The 
data in the Screening Log will not be processed centrally. 
6.1.3 Endpoints of the study 
6.1.3.1 
Primary endpoint 
Time period in days from index use of Suprasorb® CNP endo to release for oral food intake (in upper GI tract 
use) or endoscopic release for stoma relocation (in lower GI tract use). 
In case of lower GI tract use and no stoma present, time period to release for oral food intake is the relevant 
endpoint. 

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6.1.3.2 
Secondary endpoints 
1. 
Number of SAEs related to defect treatment within total observation period. 
2. 
Number of nights in hospital for therapy of index defect. 
3. 
Number of nights at the ICU during hospital stay for therapy of index defect. 
Nights at an intermediate care unit (IMC) will not count for this secondary endpoint. 
SAEs will be adjudicated by an independent Clinical Event Committee (CEC) according to standard definitions. 
Wherever reasonable, endpoints will be normalised to one year of follow-up to adapt results to varying follow-
up periods. 
“Index defect” describes for each study patient the defect(s) which lead to the clinical indication of treatment 
with Suprasorb® CNP endo system according to IFU and medical guidelines as defined in 6.3.1. 
“Index therapy” describes for each study patient the first use of Suprasorb® CNP endo for therapy of the index 
defect.  
6.1.4 Methods and timing for assessing, recording, and analysing variables 
Only data which can be obtained from routine clinical care files of the patients will be recorded. Data of routine 
clinical care visit after study enrolment will be reported in the e-CRF. Data will be derived from clinical records 
and findings, radiological assessments, observations or other sources (e.g. hospital records, clinical and office 
charts, electronic patient records, laboratory notes). 
Within this observational study timing of measures and clinical data to be reported are determined by routine 
clinical care in line with applicable medical guidelines and local policies. The study protocol just defines some 
procedural recommendations. 
6.1.5 Equipment to be used for assessing the study variables 
Only data which are obtained in routine clinical care will be recorded and reported in the eCRF. Thus, no 
special equipment differing from routine clinical care will be used to assess the study variables. 
6.1.6 Any procedures for the replacement of subjects 
No study-specific intervention is defined within this observational study which is only following routine clinical 
care. 
Patients’ written informed consent to use and process their routine clinical care data according to data privacy 
standards will be obtained prior to documentation of any patients’ data in the e-CRF. It is expected that in the 
majority of patients written informed consent to use and process data (enrolment) is provided after index ther-
apy. 
The principle for analysis of study data is intention to treat without restrictions to any subsequent course of 
follow-up. 
Thus, no necessity of any procedures for the replacement of patients is foreseeable. 
6.2 
Investigational device(s) and comparator(s) 
In this purely observational study no investigational devices will be used. However, a marketed medical device 
of interest will be used upon the investigator’s decision according to medical guidelines and local policies. All 
medical devices used in this study are CE-marked, marketed devices which will only be used within the ap-
proved IFU in the intended patient population. 

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In this purely observational study without pre-defined therapy groups, no control group is defined, thus, no 
comparator devices are used. 
Other medical devices which might be used reflect the medical decision of the investigator but are not defined 
or specified within the study protocol. 
6.3 
Subjects 
About 110 adult female and male patients with acute defects, injuries and wounds in the oesophagus or rectum 
and an indication of treatment with Suprasorb® CNP endo system according to IFU and medical guidelines will 
be enrolled. Patients’ written informed consent to use their routine clinical data according to data privacy stand-
ards must be obtained prior to documentation of patients’ data in the e-CRF. All patients in whom the device 
has been used will be followed during routine clinical practice and will visit a site only in the course of their 
routine clinical care. No additional treatment or medical examinations will be performed. 
It will be assured by means of the e-CRF system that treatments of upper GI tract and lower GI tract will be 
about equally balanced over the total study population. 
6.3.1 Inclusion criteria 
I1. ≥ 18 years of age 
I2. Acute transmural defects, injuries and wounds in oesophagus or rectum, including perforations (iatrogenic 
or spontaneous) and anastomotic insufficiencies (Index defect) 
I3. Indication of treatment with Suprasorb® CNP endo system according to IFU and medical guidelines 
I4. Signed informed consent for usage of data 
6.3.2 Exclusion criteria 
E1. Pre-existing coagulation disorders with increased risk of bleeding 
E2. Defects involving the bronchial system (bronchus/trachea/pulmo) 
E3. Any foreseeable deviation from IFU of Suprasorb® CNP endo 
E4. Known intolerance or allergy to one or more components of Suprasorb® CNP endo 
6.3.3 Criteria and procedures for subject withdrawal or discontinuation 
Patients enrolled into the study can withdraw consent for use of their data at any time for any reason without 
prejudice to further treatment or level of care. The investigator is not able to decide about the discontinuation 
of study participation of any patient. In the event that a patient withdraws consent, the date and reason for 
termination will be documented in the e-CRF according to ISO 14155:2020, section 7.10. In case of withdrawal 
of consent for use of data, no further data will be collected from the patient. The withdrawal of the informed 
consent shall not affect the use of data based on informed consent before its withdrawal. All reasonable efforts 
should be made to complete assessments and retrieve any outstanding data. 
Due to observational nature of the study no specific procedures for follow-up of subjects following the end or 
a temporary or early termination of the study are defined. All medical care after withdrawal, discontinuation or 
regular end of the observation will be provided by the treating physician according to routine clinical care. 
6.3.4 Point of enrolment (study sites) 
About 10 study sites in Germany, which are trained for the use of Suprasorb® CNP endo system treatment in 
routine clinical care, will screen eligible patients. 

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Patients will be enrolled in this observational study if an indication for Suprasorb® CNP endo treatment was 
defined by the treating physician based on routine clinical care decisions, all inclusion and no exclusion criteria 
of the study are met and written consent is given to use and process their routine clinical data according to 
applicable data privacy standards. 
It is expected that in the majority of patients written informed consent to use and process data is provided after 
routine clinical treatment of the index defect. 
6.3.5 Total expected duration of the study. 
The clinical phase of the study (first patient in to last patient out) is expected to last for 27 months with 24 
months of enrolment and 3 months of follow-up of last patient in. After about 3 months of follow-up of the last 
patient treated with index therapy and subsequent final data cleaning, global end of study will be declared. 
6.3.6 Expected duration of each subject's participation 
The mean follow-up period (from date of enrolment to end of follow-up) of all patients is expected to be about 
3 months. 
6.3.7 Number of subjects required to be included in the study 
As discussed in 3.2, the evidence for the different treatment options is very limited. Especially the patient 
populations, e.g. regarding underlying diseases, as well as the processes in the therapy are very different in 
the individual studies published. Therefore a reasonable sample size calculation is not possible at the moment. 
Thus, an interim analysis with sample size re-calculation is planned. 
The best evidence for an initial sample size calculation is provided by data of the study by Wasmann et al. 
[29], a cohort study including 334 patients with ileal defects, where EVAC therapy was compared to conven-
tional management of defect treatment. The median time to stoma relocation was estimated as 4 months in 
the EVAC group (interquartile range 3 to 6 months) versus 4 months (3 to 13 months) in the conventional 
management group. Therefore, the proportion of patients with stoma relocation after 6 months is known as 
75% in the EVAC group. Assuming a constant increasing proportion in the conventional management group 
from 4 to 13 months with 2.8% per month, a proportion of 56% stoma relocations after 6 months is expected 
for the conventional group. Even if the follow-up is set to 3 months in this study, sample size calculation can 
be based on 6 months results. 
Sample size calculation was performed with PASS 16.0.3 using a two-sided, one-sample log rank test. A group 
sequential design with the alpha spending function of O’Brien-Fleming results in a two-sided type one error of 
4.92% for the final analysis. A sample size of 99 analysable subjects achieves 80% power to detect shorter 
time to release for food intake or endoscopic release for stoma relocation (assuming a proportion of relocated 
stoma of 75% after 6 months in the EVAC group when the proportion in the historic control group is 56%). The 
expected number of events during the study with 3 months of follow-up is 13. It is assumed that the survival 
time distributions of both groups are approximated reasonable well by the Weibull distribution with a shape 
parameter of 1.00. To account for treatment switching and early drop-outs of 10%, 110 analysable patients will 
be enrolled. 
After data of complete follow-up of about half of the enrolled patients are available, an interim analysis will be 
performed and sample size will be recalculated. It is expected that until then the results of an ongoing random-
ized clinical trial comparing EVAC therapy to standard minimally invasive esophagectomy (refer to 
NCT04162860 and [22]) are available and can also be used as more reliable assumptions for sample size 
recalculation. The maximum sample size is set to 1.5 times the initial sample size, equal to 165 patients. 

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6.3.8 Estimated time needed to select this number (i.e. enrolment period) 
It is expected that about 24 months of enrolment will lead to about 110 patients enrolled. 
6.4 
Procedures 
6.4.1 Study-related procedures 
No study-specific procedures are defined in this protocol and will be performed during this observational study 
but routine clinical care procedures according to applicable medical guidelines, IFU of the devices used and 
local policy. 
“Enrolment” in this observational study means the patient is giving informed consent for use of personal med-
ical data, i.e. the legal prerequisite for being part of this clinical observation. Thus, “date of enrolment” is the 
date of the signature on informed consent. In this purely observational study consent for use of data might be 
given after index treatment because this treatment is performed in routine clinical care without any study-
specific requirements or definitions and might be performed in an acute setting. 
“Baseline visit” in this observational study is not a specific personal visit of the patient at the study site but a 
basket to document all relevant data known at baseline. Thus, medical data reported at baseline visit might 
represent patient’s status even before enrolment, e.g. data on medical history. Use of these data is covered 
by the informed consent given by the patient. 
Due to the acute defects in focus and the corresponding indication of invasive treatment in this purely obser-
vational study, “date of enrolment” (=date of informed consent for use of personal medical data) might therefore 
be after “date of index treatment”. 
“Start of observation” with respect to the objectives and endpoints of this study is the time point of the index 
treatment. 
6.4.2 Pre-Screening/check of eligibility 
Routine clinical care patients are pre-selected and diagnosed for potential eligibility of study participation based 
on existing data generated in routine clinical care which is not part of this observational study. However, all 
potentially eligible patients irrespective of their subsequent enrolment into this study will be documented in a 
screening log within the time period while the study site is open for recruitment to control for selection bias 
(refer to 6.1.2). 
6.4.3 Screening and baseline/enrolment visit (day 1 of observation) 
Patients will be screened and enrolled by contracted study sites only, i.e. expert centres. Screening of poten-
tially eligible patients will be performed within routine clinical care. Check for eligibility according to in- and 
exclusion criteria will be performed using routine clinical care data. 
Potentially eligible patients will be informed about the use of their medical data in the study. The patient will be 
given sufficient time to consider the implications of data use before deciding whether to consent. Participation 
in this study means following clinical routine care procedures, but allowing for documentation of medical data 
in a central web-based data base (e-CRF). If the patient is willing to agree, the informed consent form for data 
use will be provided for signature. As soon as signed informed consent is available, the patient has been 
enrolled into the study. 
Informed consent for use of personal medical data will often be given after the date of index treatment because 
the treatment is performed in routine clinical care. The fact of enrolment and the enrolment date will in any way 
be documented within the baseline visit. 

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After signing the consent, patients are checked for eligibility according to in- and exclusion criteria by the 
participating sites consecutively to minimise selection bias. Study relevant data will be reported in the e-CRF. 
The e-CRF system will automatically display the patient ID as consecutive number across all participating 
study sites, i.e. without reference to the recruiting site. 
The following data items will be documented of each participating patient at enrolment: 
 
Demographic data 
 
Patient’s physical status 
 
Medical history 
 
Relevant concomitant medication and diseases 
Data on the entire clinical stay for treatment of the index defect will be documented. 
6.4.4 Treatment of the index defect 
The decision of treatment of the index defect lies with the treating physician in routine clinical care. Indication 
as well as initiation of treatment should follow applicable medical guidelines, local clinical care policy and the 
IFUs of the devices used.  
Initiation of treatment might start as routine clinical care procedure before enrolment into the study (i.e. in-
formed consent of the patient) but data can be entered into the e-CRF after signed informed consent is avail-
able (i.e. after enrolment), only. 
 
Primary EV therapy is defined as the utilisation of EVT as first-line therapy for perforation or leak. 
 
Rescue EV therapy is defined as EVT placement following failure of definitive surgical repair for a perfo-
ration or leak. 
 
Defect closure following EVT placement is defined as 1) no evidence of continued leak under direct 
endoscopic visualization and 2) a negative oesophagram following discontinuation of EVT therapy. 
Data regarding index defect, related therapy and outcome following EVT placement will be documented in the 
e-CRF at the Index-treatment visit. 
The following data items will be documented of each participating patient at the index-treatment visit: 
 
Data of index treatment and related therapy (defect size, type and location of perforation, pre-existing 
pathology, ASA-classification, Perforation Severity Score (PSS), primary or rescue EVT application, type 
of endo-sponge placement, type of surgical repair, time to placement of EVT following diagnosis, number 
of EVT changes, number of days between EVT changes, total length of EVT therapy, relevant laboratory 
parameters) 
 
Outcome of index treatment (including 30-day mortality, closure interventions following treatment of index 
defect, hospital length of stay (LOS), ICU LOS, EVT therapy-specific findings (e.g. migration, dislodgement, 
erosion), time to oral diet initiation / endoscopic release for stoma relocation following successful defect 
closure). 
 
6.4.5 Follow-up (FU) visits 
Every patient will be followed for 3 months after discharge after index treatment. 
In line with routine clinical care, at least one personal follow up visit should take place within 3 months of follow 
up. To ensure comparability of data, in case this follow up visit has not been performed after 3 months (± 2 
weeks)  in addition a phone call with the patient should provide final information to be documented in the FU 
visit (phone) of the e-CRF. 

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At the FU visits the following data from clinical routine will be documented in the e-CRF (if available): 
 
Patient status 
 
Relevant concomitant medication and other treatment 
 
Safety related events: SAEs (including SADEs), AEs of special interest (including ADEs) and DD 
6.4.6 Visit table 
Assessments* 
Baseline visit 
Index-Treatment 
FU visits 
Informed consent for data use 
X 
 
 
In- and Exclusion criteria 
X 
 
 
Demographic data 
X 
 
 
Medical history 
X 
 
 
Patient’s status 
X 
 
X** 
Medication/other treatment 
X 
X 
X** 
Concomitant diseases 
X 
 
 
Data regarding index treatment and related 
therapy 
 
X 
 
Outcome of index treatment 
 
X 
 
Safety related events (SAEs, SADEs, ADEs, 
DD) 
 
X 
X 
* If data are available in routine clinical care. 
** Only if the FU-Visit is performed on site 
6.4.7 Activities performed by sponsor representatives (excluding monitoring) 
The sponsor will define potentially eligible hospitals and physicians for participation in this study based on his 
knowledge on their training and expertise in use of the Endoscopic (Endoluminal) Vacuum Therapy in the 
gastrointestinal tract treatment in routine clinical care. Eligibility of each study site according to standards fol-
lowing ISO 14155:2020 will be assessed and documented by the responsible CRO. 
No other activities of sponsor representatives related to this study will be performed. 
6.4.8 Known or foreseeable factors that may compromise the outcome of the study or the interpretation of 
results 
This clinical study is purely observational. All procedures and therapies are representing routine clinical care 
based on individual decisions by the treating physician and are not given as standardised procedures in the 
study protocol. It is expected that observed variations in diagnosis and treatment of defects of interest will be 
further compared to controlled clinical trials with given standards. Selection bias will be controlled by means of 
data collected about the site itself and pooled details about their patients of interest in routine clinical care. 
The data of this study represent routine clinical care of patients with acute defects, injuries and wounds in the 
oesophagus or rectum, including perforations (iatrogenic or spontaneous) and anastomotic insufficiencies with-
out limitations normally given by protocol definitions of controlled clinical trials. Thus, the generalizability of 
results is deemed to be higher compared to those of controlled clinical trials. However, due to the expected 

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larger range of variations in procedures and therapies the level of statistical significance is expected to be 
lower but allowing for generation of hypotheses which might be investigated in subsequent clinical research 
projects. 
6.5 
Monitoring plan 
No routine onsite monitoring is initially planned within this non-interventional, observational study. Since only 
observation of routine clinical care without any protocol-defined interventions will be performed, the safety and 
well-being of study patients is the scope of routine clinical care. Thus, onsite monitoring could be justified for 
double-check of completeness and quality of data, only. Data quality will primarily be controlled by means of 
statistical checks on data available for all study sites allowing to detect outliers, extremes and deviation in 
distribution of data. In case of suspicious findings, on-site visits in corresponding sites might be performed. 
7. 
Statistical considerations 
In this observational study the time period from index therapy to release for oral food intake (in upper GI tract 
use) or endoscopic release for stoma relocation (in lower GI tract use) will be compared to published historic 
controls. For this, the time period is compared to published data of other EVAC and conventionally managed 
therapy, especially data from Wasmann et al. [29]. In addition, after half of the patients with complete follow-
up, an interim analysis will be performed and sample size will be recalculated. It is expected that until then the 
results of a randomized clinical trial comparing an EVAC therapy to standard minimally invasive oesophagec-
tomy (refer to NCT04162860 and [22]) will be available for adaptation of assumed confidence intervals and 
sample size (see 6.3.7). The hypothesis of superiority against conventionally managed therapy will be tested 
confirmatory. 
For primary analysis a one-sample log-rank test will be used, comparing the observed number of events to the 
expected number of events of the control groups. The two-sided type-one error is 0.54% for the interim analysis 
and 4.92% for the final analysis. 
Data from all study sites will be pooled for analysis. Standard statistical methods will be used to analyse all 
data. Continuous variables will be summarized using the number of observations, mean, median, standard 
deviation, minimum and maximum values. Categorical variables will be summarized using the number of ob-
servations and percentages. 
A separate Statistical Analysis Plan will be prepared prior to the start of data analysis, detailing the statistical 
analyses methods that will be used. 
8. 
Data management 
Study and site management as well as data cleaning, data management and statistical analysis was delegated 
by the sponsor to CRI – The Clinical Research Institute, Munich, Germany, as responsible Contract Research 
Organisation. 
Applicable national and international legal requirements for data handling and data archiving will be met. Clin-
ical data will be collected using the web-based MARVIN system, a GCP and 21 Code of Federal Regulations 
(CFR) 11 compliant Electronic Data Capture (EDC) and Clinical Trial Management System (CTMS) software 
based on Clinical Data Interchange Standards Consortium (CDISC) data standards. Medical data within this 
study will be recorded directly in the e-CRF at the site without use of paper documents. The e-CRF system is 
available for all participants in the study 24 hours/7 days during the course of the study. Before closure of the 
study, all participating sites will be provided media with PDFs of all e-CRF data ever entered in the correspond-
ing site together with all related metadata (e. g. audit trail, data queries). 

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8.1 
Electronic case reporting form 
The e-CRF has been approved by the SC. It is identical for each site and is provided in German language. 
Data will also be collected about the site itself (e.g. type of institution and other administrative data), and basic, 
pooled details about its patients in focus to allow for control of selection bias. 
8.2 
Personal data and data protection 
All data obtained in the context of this observational clinical study are subject to data protection according to 
EU GDPR. This applies to patients' data as well as to investigators' personal data which may be included in 
any database of the sponsor or the CRO. Data protection processes and responsibilities according to EU 
GDPR are defined in agreements on joined control of data between study sites and the sponsor as well as in 
an agreement of data processing between the sponsor and the CRO. 
The storage of data for statistical assessment shall likewise be performed only under the patient’s study num-
ber. Only authorised staff members in each site can assign identifiers to personal data. If personal data are 
stored and processed, requirements for data protection will be followed. The study database is centrally stored 
on redundant servers in Germany provided by the e-CRF system vendor and under the control of the CRO. 
All recorded data will be pseudonymised for storage in the central database during the course of the study. As 
the decoding information is held only by the treating study sites, nobody else will know the identity of the 
participating patients. After the end of the project, the data will be deleted from the vendor’s servers and trans-
ferred to the sponsor where it will be stored according to regulatory requirements and sponsor’s SOPs. 
Data will only be collected and processed to reach the goals of the study. Personal data of the patient are 
demographic data (e.g. height, weight, data on comorbidities, data on current therapy), SAEs and therapy 
data. Data will be transferred to the CRO (database management, data cleaning, data analysis), to sponsor’s 
subsidiaries within the EU and to the scientific SC. 
The patient will be informed about the study and her/his rights in terms of data usage, data storage, correction 
of data and deletion of stored data. 
8.3 
Completion of Case Report Forms 
All medical data within this study will be recorded directly in the e-CRF without the use of paper CRF. The 
investigator must ensure the accuracy, completeness, legibility and timeliness of data reported in the e-CRF 
and of all required clinical reports (e. g. in case of SAEs). Any change or correction to the data in the e-CRF 
must be explained as a prerequisite of the e-CRF system. Any change or correction to an e-CRF item will 
automatically be tracked (audit trail), recording the person logged-in as well as the time stamp of the change 
and the reason for change. The e-CRF system will not accept changes without given reason. The history of 
changes to a single item including original entries is always visible to the responsible local research team and 
to the CRO.  
Data reported in the e-CRF that are derived from source documents should be consistent with the source 
documents or existing discrepancies should be explained. Upon entry into the e-CRF the data will be automat-
ically stored in the central study database in pseudonymised form. 
8.3.1 Data documented by study sites 
Data will be derived from clinical routine care records and findings, observations or other sources (e.g. hospital 
records, clinical and office charts, electronic patient records, laboratory notes, recorded data from automated 
devices, patient files, laboratories and medico technical departments). In cases where data are collected while 
speaking to the patient, the e-CRF is the source document (if the patient’s answer is documented there without 
prior documentation on paper). 
SAEs during FU will be assessed by the treating investigator. 

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8.3.2 Quality control 
Quality control is defined as the operational techniques and activities undertaken within the quality assurance 
system to verify that the requirements for quality of the study-related activities have been fulfilled. Quality 
control should be applied to each stage of data handling to ensure that all data are reliable and have been 
processed correctly. 
Quality assurance is defined as the planned and systematic actions that are established to ensure that the 
study is performed, and the data generated, documented (recorded) and reported, in compliance with GCP 
according to ISO 14155:2020 and applicable regulatory requirements. 
Source Data 
Source data are defined as all information obtained in clinical routine care and stored in original records and 
certified copies of original records of clinical findings, observations or other activities in a clinical study neces-
sary for the reconstruction and evaluation of the study. Source data are contained in source documents (orig-
inal records or certified copies). 
Source Documents 
Source documents are defined as original documents, data and records in clinical routine care (e.g. hospital 
records, clinical and office charts, laboratory notes, memoranda or evaluation check lists, pharmacy dispensing 
records, recorded data from automated instruments, copies or manuscripts certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x- rays, patient files, rec-
ords kept at pharmacy, at the laboratories and at medico technical departments). 
Access to Source Data/Document 
The investigator will permit, and participating patients will consent for, study-related monitoring, audits, EC 
review and regulatory inspections, providing direct access to primary patient data (i.e. source data) that support 
data in the e-CRFs, i.e. general practice charts, hospital notes, appointment books, original laboratory records, 
etc. Because this is a patient confidentiality issue, access to such data must form part of the Informed Consent 
Form to be signed by the patient. 
Direct Access 
Direct access is defined as the permission to examine, analyse, verify and reproduce any records and reports 
that are important to the evaluation of a clinical study. No identifiable patient data can be released from a site. 
Any party (e.g. domestic and foreign regulatory authorities, the sponsor and/or authorised representatives of 
the sponsor such as monitors and auditors) with direct access should take all reasonable precautions within 
the constraints of the applicable regulatory requirements to maintain the confidentiality of patient identities and 
sponsor proprietary information. 
Audits 
An audit is a systematic and independent review of study-related activities and documents to determine 
whether the validated study-related activities were conducted and the data were recorded, analysed and ac-
curately reported according to the protocol, designated standard operating procedures (SOP), GCP according 
to ISO 14155:2020 and applicable regulatory requirements. An independent audit at the site may take place 
at any time during or after the study. 
9. 
Amendments to the study protocol 
Amendments to study protocol will be sent to each corresponding EC. In case of substantial amendments to 
protocol the vote of the responsible EC is a prerequisite before coming into force for corresponding study sites. 
In case of non-substantial amendments to protocol modifications will be implemented as soon as the sponsor 
and the SC signed the document. 

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Regulatory bodies are not involved in this non-interventional, observational study. Thus, amendments to pro-
tocol will not be submitted to them. 
10. Deviations from study protocol 
Protocol deviations are any unapproved changes, deviations or departures from study design or procedures 
of a research project that are under the investigator’s control and that have not been reviewed and approved 
by the SC. 
This clinical study is purely observational. All procedures and therapies are performed as routine clinical care 
based on individual decisions by the treating physician and are not defined in the study protocol. This includes 
timing of procedures and follow-up visits as well as measures available for reporting which are defined as 
recommendations in the study protocol. Deviations from study protocol might therefore primarily occur for in- 
and exclusion criteria. 
11. Device accountability 
No investigational devices are used, thus, device accountability is not applicable. 
12. Statements of compliance 
This clinical study is purely observational. All therapies used are decided individually by the treating physician 
and are not pre-defined by the study protocol. All therapies used within this study have to be in line with their 
marketing authorisation, i.e. IFU. 
Participation in this study does not pose additional risks or benefits compared to routine clinical practice be-
cause only data created within routine clinical care will be documented in this observational study, no study-
specific interventions will be performed. All therapeutic decisions and procedures should be in accordance with 
routine clinical care following applicable medical, ethical and regulatory standards, e.g. ICH-GCP according to 
ISO 14155:2020. 
No study-specific insurance is provided for patients who agree to the use of their data within this study. 
Before initiating the study in a study site, a positive vote of the corresponding EC will be obtained. 
This clinical study is industry funded and solely financed by the sponsor. The costs necessary to perform the 
study, i.e. to cover the time spent by site staff for documentation work, will be agreed upon with each investi-
gator and will be documented in a separate financial agreement which will be signed by the site and the CRO 
on behalf of the sponsor, prior to the study commencing. 
13. Informed consent process 
All clinical data needed to evaluate the potential eligibility of a patient before study inclusion are to be performed 
during routine clinical care and are therefore not considered to be part of study related procedures. 
A signed, EC approved informed consent form for transfer, processing and use of personal medical data, 
written in accordance with applicable data privacy regulations, will be obtained from every patient prior to any 
transfer of personal data to the e-CRF. The patient will be given sufficient time to consider the implications of 
consenting for transfer, processing and use of personal medical data before deciding whether to agree. 
Patients undergoing the procedures of interest in this study will often be in a clinical situation requiring imme-
diate therapy without any delay. In addition, it is expected that potential study patients might not be able to 
give informed consent on the use of their personal data at the time of physician’s decision on the primary 

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intervention procedure of interest. Since this clinical study is purely observational, all therapies used are de-
cided individually by the treating physician in routine clinical care in line with medical guidelines and the IFUs 
of the devices used but not pre-defined in the study protocol. Thus, informed consent for use of personal data 
will be given subsequent to the primary intervention procedure of interest but before any data transfer to the 
e-CRF. 
Should there be any modifications to the protocol, such that this would directly affect the patient’s consent for 
transfer, processing and use of their personal medical data in the study, an addendum to the informed consent 
form specifying the modification must be compiled and the active patients must agree to sign this addendum 
indicating that they also agree to the modifications within the study. 
A signed copy of the patient’s informed consent form must be maintained in the study file on site, a copy of the 
signed informed consent form must be provided to the study patient. The patient’s permanent medical records 
should indicate the patient's study participation. 
14. Adverse events, adverse device effects and device deficiencies 
SAEs will be documented following ISO 14155:2020 and reported in accordance with applicable national 
standards. Since the study is observational, all therapies and procedures represent routine clinical care in line 
with applicable medical guidelines, market authorisations and corresponding IFUs. Since no risks or benefits 
compared to routine clinical care will be added, the rate of non-serious AEs will be identical to routine clinical 
care. Thus, non-serious AEs will not be documented within this study but AEs of special interest (AEoSI), only 
(refer to section 14.1). 
14.1 Definitions 
Adverse Event (AE): 
Is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including ab-
normal laboratory findings) in subjects, users or other persons, in the context of a clinical investigation, whether 
or not related to the investigational medical device. This definition includes events that are anticipated as well 
as unanticipated events and those occurring in the context of a clinical investigation related to the investiga-
tional device, the comparator or the procedures involved. For users or other persons, this definition is restricted 
to events related to investigational medical devices. A newly diagnosed concomitant disease is also considered 
an AE. 
AE of special interest (AEoSI) 
Potential complication of index therapy: 
 
Iatrogenic injury of the mucosa; 
 
Any bleeding, appearance of fistula or abscess, pneumonia, peritonitis, or mediastinitis as a symptom of 
the treatment; 
 
Occurrence of stricture / stenosis during the follow-up. 
An independent CEC will review AEoSIs based on coded (pseudonymized) copies of corresponding medical 
files to assess if they fulfil criteria for 
 
 
 

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Serious Adverse Event (SAE): 
A SAE is any untoward medical occurrence that 
 
led to death, 
 
led to serious deterioration in the health of the subject, that either resulted in 
 a life-threatening illness or injury, or 
 a permanent impairment of a body structure or a body function, or 
 hospitalisation or prolongation of patient hospitalisation, or 
 medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to 
a body structure or a body function, 
 a chronic disease, 
 
led to foetal distress, foetal death or a congenital abnormality or birth defect. 
More than one of the above criteria can be applicable to each event. 
These characteristics/consequences have to be considered at the time of the event. For example, regarding a 
life-threatening event, this refers to an event in which the subject was at risk of death at the time of the event. 
It does not refer to an event which hypothetically might have caused death if it were more severe. 
NOTE: 
 
The index treatment itself, 
 
a planned hospital overnight stay in follow-up for review of index defect, 
 
an elective hospitalisation (e.g. surgery) verifiably planned before signing consent  
 
overnight survey visits (e.g. sleep lab) 
are not considered as SAEs if no additional medical events occur which fulfil criteria of a SAE. 
An independent CEC will review SAEs (and AEoSIs) based on coded (pseudonymized) copies of correspond-
ing medical files to assess if they fulfil criteria for 
 
defect treatment complication or 
 
being related to defect treatment. 
Life-threatening 
The definition of a SAE refers to an event in which the patient was at risk of death at the time of the event. It 
does not refer to an event which hypothetically might have caused death if it was more severe. 
Hospitalisation 
 
Hospitalisation within this protocol is defined as inpatient care for more than one calendar day (overnight 
stay) for any cause. Overnight survey visits (e.g. sleep lab) are not considered “hospitalisation”. 
 
Hospitalisation for therapy of index defect follows within this protocol the definition in 6.3.1. 
The investigator will document in the e-CRF for each hospitalisation if he classifies it as “for therapy of index 
defect”. 
Because hospitalisation decisions might be subject to local practices, social considerations, bed availability, 
and so on, hospitalisations for SAEs will be reviewed by an independent CEC based on coded (pseudony-
mized) copies of corresponding medical files to assess the reason and appropriateness of each hospitalisation, 
i.e. whether it is “for therapy of index defect”. 

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14.2 Device Related Adverse Events 
Within this PMCF study adverse events related to the IP will be recorded and reported.  
14.2.1 Device Deficiency (DD) 
DD means any inadequacy in the identity, quality, durability, reliability, safety or performance of an investiga-
tional device, including malfunction, use errors or inadequacy in information supplied by the manufacturer. 
Since the study is observational, no investigational medical product will be used but all therapies and proce-
dures represent routine clinical care in line with applicable medical guidelines, market authorisations and cor-
responding IFUs. Treating physicians have to report DDs related to medical devices or therapies to the corre-
sponding manufacturers of devices concerned. Reporting duties of manufacturers of devices used within this 
observational study have to follow routine procedures relevant for marketed medical devices. 
14.2.2 Adverse Device Effect (ADE) 
Any untoward and unintended response to a medical device. This definition includes AEs resulting from insuf-
ficient or inadequate instructions for use, deployment, implantation, installation, or operation, or any malfunc-
tion of the investigational medical device. It also includes any event resulting from use error or from intentional 
misuse of the investigational medical device. Since the study is observational, no investigational medical prod-
uct will be used but all therapies and procedures represent routine clinical care in line with applicable medical 
guidelines, market authorisations and corresponding IFUs. Treating physicians have to report ADEs related to 
medical devices or therapies to the corresponding manufacturers of devices concerned. Reporting duties of 
manufacturers of devices used within this observational study have to follow routine procedures relevant for 
marketed medical devices. 
14.2.3 Serious Adverse Device Effect (SADE) 
Any device deficiency that might have led to a SAE if appropriate action had not been taken, intervention had 
not occurred, or circumstances had been less fortunate, shall be documented throughout a clinical investiga-
tion and appropriately managed by the sponsor. Since the study is observational, no investigational medical 
product will be used but all therapies and procedures represent routine clinical care in line with applicable 
medical guidelines, market authorisations and corresponding IFUs. Treating physicians have to report ADEs 
related to medical devices or therapies to the corresponding manufacturers of devices concerned. Reporting 
duties of manufacturers of devices used within this observational study have to follow routine procedures rel-
evant for marketed medical devices. 
14.3 Recording and reporting of reportable events 
The following events are considered reportable events in accordance with MDR Art. 80(2): 
 
any SAE that has a causal relationship with the investigational device, the comparator or the investigation 
procedure or where such causal relationship is reasonably possible; 
 
any DD that might have led to a SAE if appropriate action had not been taken, intervention had not oc-
curred, or circumstances had been less fortunate; 
 
any new findings in relation to any event referred to in the points above. 
Since this study is observational, no investigational medical product will be used but all therapies and proce-
dures represent routine clinical care in line with applicable medical guidelines, market authorisations and cor-
responding IFUs. Thus, causal relationships of events to an investigational device or procedure will not be 
assumed. However, irrespective of this study, treating physicians have to report AEs related to medical devices 
or therapies to the corresponding manufacturers of devices concerned. Reporting duties of manufacturers of 

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devices used within this observational study have to follow routine procedures relevant for marketed medical 
devices. 
Information on all SAEs which occurred after start of index treatment, whether related or not related to index 
treatment, must be collected. The investigator should specify and report in the e-CRF the nature of the sign or 
symptom leading to the SAE, the date of onset of the sign or symptom, the date of resolution of the specific 
event (not of the underlying disease), the intensity, interventions performed (if any), the relationship to index 
treatment, and the outcome. 
All SAEs must be reported expeditiously by the investigator to the sponsor through the SAE section of the e-
CRF within 24 hours of becoming aware of the event. A SAE form within the e-CRF should be completed 
for any event where doubt exists regarding its status of seriousness. As a minimum, the investigator has to fill 
out the following items in the internet-based SAE form within 24 hours of becoming aware of the event: 
 
Type of event 
 
Description 
 
Date of onset 
 
Criteria for seriousness 
As soon as further information regarding the event is available, the investigator should complete the documen-
tation in the e-CRF and sign it electronically. Copies of relevant medical documents, of reports regarding ex-
aminations carried out and/or diagnostic findings should be digitally provided to the CRO after adequate blind-
ing of patient identifiers, only. 
Follow-up of any SAE that is fatal or life threatening should be digitally provided immediately but no later 
than within 2 calendar days of becoming aware of the event. 
Any SAE reporting (initial reporting and follow-up information on e.g. changes of an ongoing SAE’s intensity 
or relationship to the investigational product or outcome) is done through the SAE section of the e-CRF. An 
automated e-mail notification system within the e-trial management system will inform the CRO instantane-
ously, thus, no extra SAE form needs to be transmitted but the CRO will receive an automated digital notifica-
tion on the SAE at the same time of the data being documented or changes of relevant SAE data being made 
in the e-CRF. 
The investigator shall report in detail all SAEs as well as AEoSIs. 
14.3.1 Definition of Intensity 
Be aware that intensity of an AE and its seriousness are independent definitions, e.g. an AE might be serious 
but mild in intensity or vice versa. 
Intensity 
Definition 
Mild 
Patient is aware of signs and symptoms but they are easily tolerated 
Moderate 
Signs/symptoms cause sufficient discomfort to interfere with usual activities 
Severe 
Patient is incapable to work or perform usual activities 
14.3.2 Definition of Causality 
The sponsor and the investigators will use the following definitions to assess the relationship of SAEs to the 
index therapy (devices used and procedure itself). 
 
 

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Not related 
Relationship to index therapy can be excluded when: 
 
the event has no temporal relationship with the use of the devices or the procedures; 
 
the SAE does not follow a known response pattern to the index therapy (if the response pattern is previ-
ously known) and is biologically implausible; 
 
the discontinuation of the index therapy 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 SAE; 
 
the event involves a body-site or an organ that cannot be affected by the index therapy; 
 
the SAE can be attributed to another cause (e.g. an underlying or concurrent illness/ clinical condition, an 
effect of other devices, drugs, treatments or other risk factors). 
In order to establish the non-relatedness, not all the criteria listed above might be met at the same time, de-
pending on the type of device/procedures and the SAE. 
 
Possible 
The relationship with the index therapy 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 other devices, drugs or 
treatments). Cases where relatedness cannot be assessed, or no information has been obtained should also 
be classified as possible. 
 
Probable 
The relationship with the index therapy seems relevant and/or the event cannot be reasonably explained by 
another cause. 
 
Causal relationship 
The SAE is associated with the index therapy beyond reasonable doubt when: 
 
the event is a known side effect of the index therapy or of similar devices and procedures; 
 
the event has a temporal relationship with the index therapy; 
 
the event involves a body-site or organ that 
 the index therapy is applied to; 
 the index therapy has an effect on; 
 
the SAE follows a known response pattern to the index therapy (if the response pattern is previously 
known); 
 
the discontinuation of the index therapy (or reduction of the level of activation/exposure) and reintroduction 
of its use (or increase of the level of activation/exposure), impact on the SAE (when clinically feasible); 
 
other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of other 
devices, drugs or treatments) have been adequately ruled out; 
 
harm to the subject is due to error in the index therapy. 
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 SAE. 

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The sponsor of the study is responsible for reporting of reportable events to regulatory bodies according to his 
duties in routine clinical care. No specific reporting requirements to regulatory bodies are defined within this 
observational study. The reporting will be done according to MDR and national laws as serious incidents (of 
marked medical devices) by the Person Responsible for Regulatory Compliance-Vigilance (PRRC-V) of the 
sponsor. 
15. Vulnerable population 
Patients undergoing the procedures of interest in this study will often be in a clinical situation requiring imme-
diate therapy without any delay. In addition, it is expected that potential study patients might not be able to 
give informed consent on the use of their personal data at the time of physician’s decision on the primary 
intervention procedure of interest. Since this clinical study is purely observational, all therapies used are de-
cided individually by the treating physician in routine clinical care in line with medical guidelines and the IFUs 
of the devices used but not pre-defined in the study protocol. Thus, informed consent for use of personal data 
will be given subsequent to the primary intervention procedure of interest but before any data transfer to the 
e-CRF. 
16. Suspension or premature termination of the study 
The SC may decide discontinuation of the study if patients cannot be enrolled in sufficient numbers within a 
certain time period. 
The sponsor in collaboration with the SC has the right to close local study sites for enrolment of further patients 
if data quality and completeness is out of range, if the site does not comply with the study protocol or decisions 
of the committees or if the site remains inactive for several months. Such decisions will always be taken on a 
case-by-case basis and after corresponding reminders to the local study team. 
17. Publication policy 
Study results will be pooled across all participating sites for the purpose of publication that will be coordinated 
by the sponsor. Preparation of a comprehensive publication will occur at the completion of the study, but the 
sponsor may, at its discretion, coordinate an additional, interim publication. The order of authorship will be 
determined by the sponsor and will be based in part on the number of qualified and completing patients at 
each site. 
An investigator intending to publish results of the study must provide the sponsor with a copy of any proposed 
publication, abstract, or presentation at least 60 days prior to submission for publication or presentation. The 
sponsor will have the right to object to the publication, abstract, or presentation if, in the sponsor’s reasonable 
opinion, such publication (i) contains confidential information; or (ii) will adversely affect any intellectual prop-
erty or proprietary right of the sponsor. In the event of an objection by the sponsor, the investigator must either 
modify or delay the publication, abstract, or presentation for a period requested by sponsor not to exceed 
ninety (90) days to permit the sponsor to re-dress or mitigate risks. 
Investigators and sites must acknowledge the sponsor in all publications or presentations resulting from this 
study and provide any required disclosures. 
All relevant measures for transparency of clinical studies, and especially the recommendations of the editors 
of the major medical journals, will be met. 
 
 

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18. Bibliography 
1. 
Ahrens, M., et al., Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective 
pilot study. Endoscopy, 2010. 42(9): p. 693-8. 
2. 
Arezzo, A., et al., Endoluminal vacuum therapy for anastomotic leaks after rectal surgery. Tech Colo-
proctol, 2010. 14(3): p. 279-81. 
3. 
Arezzo, A, et al., Long-term efficacy of endoscopic vacuum therapy for the treatment of colorectal anas-
tomotic leaks. Dig Liver Dis. 2015;47(4): p. 342-5.  
4. 
Bludau, M., et al., Management of upper intestinal leaks using an endoscopic vacuum-assisted closure 
system (E-VAC). Surg Endosc, 2014. 28(3): p. 896-901. 
5. 
Borejsza-Wysocki, M., et al., Endoscopic vacuum-assisted closure system (E-VAC): case report and 
review of the literature. Videosurgery and other Miniinvasive Techniques, 2015. 10(2): p. 299-310. 
6. 
Brangewitz, M., et al., Endoscopic closure of esophageal intrathoracic leaks: stent versus endoscopic 
vacuum-assisted closure, a retrospective analysis. Endoscopy, 2013. 45(6): p. 433-8. 
7. 
Hausen, A., et al., Erfolgreiche endoskopisch-endoluminale Vakuumtherapie von iatrogenen und spon-
tanen Perforationen des distalen Ösophagus. Z Gastroenterol, 2015. 53(08): p. KG348. 
8. 
Heits, N., et al., Endoscopic endoluminal vacuum therapy in esophageal perforation. Ann Thorac Surg, 
2014. 97(3): p. 1029-35. 
9. 
Keskin, M., et al., Effectiveness of Endoluminal Vacuum-assisted Closure Therapy (Endosponge) for the 
Treatment of Pelvic Anastomotic Leakage After Colorectal Surgery. Surg Laparosc Endosc Percutan 
Tech, 2015. 25(6): p. 505-8. 
10. Kühn F, et al. Endoscopic vacuum therapy for the treatment of colorectal leaks - a systematic review 
and meta-analysis Int J Colorectal Dis 2022 Feb; 37(2): 283-292 
11. Laukoetter, M.G., et al., Successful closure of defects in the upper gastrointestinal tract by endoscopic 
vacuum therapy (EVT): a prospective cohort study. Surg Endosc, 2017. 31(6): p. 2687-2696. 
12. Loske, G. Müller, M, Vacuum Therapy of an Esophageal Anastomotic Leakage – A Case Report, Zen-
tralbl Chir 2009; 134: p. 267–270. 
13. Loske G, Schorsch T, Müller C. Endoscopic vacuum sponge therapy for esophageal defects. Surg En-
dosc. 2010;24(10): p. 2531-5. 
14. Loske, G., et al., Spontaneous perforation of an intramural esophageal pseudodiverticulosis treated with 
intraluminal endoscopic vacuum therapy using a double-lumen vacuum drainage with intestinal feeding 
tube. Endoscopy, 2016. 48 Suppl 1: p. E154-5. 
15. Loske, G., et al., Endoscopic intraluminal vacuum therapy of duodenal perforation. Endoscopy, 2010. 
42 Suppl 2: p. E109. 
16. Loske, G., et al., Intraluminal and intracavitary vacuum therapy for esophageal leakage: a new endo-
scopic minimally invasive approach. Endoscopy, 2011. 43(6): p. 540-4. 
17. Loske, G., et al., Intraluminal endoscopic vacuum therapy in a case of ischemia of the blind end of the 
jejunal loop after Roux-en-Y gastrectomy. Endoscopy, 2014. 46 Suppl 1 UCTN: p. E575-6. 
18. Loske G. Endoscopic negative pressure therapy of the upper gastrointestinal tract. Chirurg 2019; 90, 1–
6. 
19. Mees, S.T., et al., Endo-vacuum assisted closure treatment for rectal anastomotic insufficiency. Dis Co-
lon Rectum, 2008. 51(4): p. 404-10. 

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20. Mennigen, R., et al, Comparison of endoscopic vacuum therapy versus stent for anastomotic leak after 
esophagectomy. Journal of Gastrointestinal Surgery, 2015, 19(7), p. 1229-1235 
21. Moschler, O. and Muller, M., Endoluminal vacuum therapy for iatrogenic perforation of the proximal 
esophagus. Z Gastroenterol, 2014. 52(3): p. 281-4. 
22. Müller, PC, et al., Pre-Emptive Endoluminal Negative Pressure Therapy at the Anastomotic Site in Min-
imally Invasive Transthoracic Esophagectomy (the preSPONGE Trial): Study Protocol for a Multicenter 
Randomized Controlled Trial. Int J Surg Protoc. 2021 Mar 18;25(1): p. 7-15. doi: 10.29337/ijsp.24. 
23. Richter F. and al. Eso-Sponge® for anastomotic leakage after oesophageal resection or perforation: 
outcomes from a national, prospective multicentre registry, BJS Open 2022 Mar 8;6(2) 
24. Schniewind, B., et al., Endoscopic endoluminal vacuum therapy is superior to other regimens in manag-
ing anastomotic leakage after esophagectomy: a comparative retrospective study. Surg Endosc, 2013. 
27(10): p. 3883-90. 
25. Smallwood, N.R., et al., The use of endoluminal vacuum (E-Vac) therapy in the management of upper 
gastrointestinal leaks and perforations. Surg Endosc, 2016. 30(6): p. 2473-80. 
26. Strangio, G., et al., Endo-sponge therapy for management of anastomotic leakages after colorectal sur-
gery: A case series and review of literature. Dig Liver Dis, 2015. 47(6): p. 465-9. 
27. Turkyilmaz, A., et al., The management of esophagogastric anastomotic leak after esophagectomy for 
esophageal carcinoma. Dis Esophagus, 2009. 22(2): p. 119-26. 
28. Wallstabe, I., et al., Endoluminal vacuum therapy for anastomotic insufficiency after gastrectomy. En-
doscopy, 2010. 42 Suppl 2: p. E165-6. 
29. Wasmann, KA, et al., Endo-sponge Assisted Early Surgical Closure of Ileal Pouch-anal Anastomotic 
Leakage Preserves Long-term Function: A Cohort Study. J Crohns Colitis. 2019 Dec 10;13(12): p. 1537-
1545. doi: 10.1093/ecco-jcc/jjz093. 
30. Wedemeyer J. et al Management of major postsurgical gastroesophageal intrathoracic leaks with an 
endoscopic vacuum-assisted closure system. Gastrointest Endosc 2010 Feb;71(2): p. 382-6. 
31. Weidenhagen, R., et al., Endoluminal vacuum therapy for the treatment of anastomotic leakage after 
anterior rectal resection. Rozhl Chir, 2008. 87(8): p. 397-402. 
32. Zhang CC, Liesenfeld L, Klotz R, Koschny R, Rupp C, Schmidt T, Diener MK, Müller-Stich BP, Hackert 
T, Sauer P, Büchler MW, Schaible A. Feasibility, effectiveness, and safety of endoscopic vacuum ther-
apy for intrathoracic anastomotic leakage following transthoracic esophageal resection. BMC Gastroen-
terol. 2021;21(1): p. 72. 
 
 
 

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Annex 1. List of stand-alone documents 
No. 
Title 
1. 
List of study sites and principal investigators 
2. 
List of SC members 
3. 
List of CEC members 
 
 
 

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Annex 2. Milestones 
Section 
 
Tasks 
Date 
Draft study planning 
Draft Protocol 
24.07.2019 
Final study planning 
Final protocol 
07.12.2023 
Study preparation 
e-TMS, e-CRF; other study relevant documentation 
01.08.2022 
Start of site selection, site contacts, site evaluation 
01.08.2022 
First EC submission 
15.12.2023 
Study initiation 
Start of site contracting 
15.12.2023 
Start of supply of sites with study materials, start of 
initiation visits  
15.02.2024 
Start of recruitment period (FPI)  
15.02.2024 
End of recruitment period (LPI)  
14.02.2026 
Study duration 
End of follow-up of last patient 
14.05.2026 
Median follow-up period of all patients 
3 Months 
Database lock 
End of final data cleaning 
14.06.2026 
Final analysis 
Results to be presented to SC 
15.06.2026