Suture Techniques to Reduce the Incidence of Incisional Hernia After Midline Laparotomy; Long-Term Follow-Up of the STITCH Trial
Phase: NA
Conditions: Surgery, Incisional Hernia, Wound Infection, Fascial Dehiscence, Pain, Quality of Life
Sponsor: Erasmus Medical Center

 
 
LTFU-STITCH trial 
 
 
 
 
 
 
 
 
 
 
 
 
LTFU-STITCH trial 
Suture Techniques to reduce the Incidence of The incisional 
Hernia, the Long-Term Follow-Up of the STITCH trial 
 
 
STUDY PROTOCOL 
31-08-2023 
 
REPAIR Research Group 
Erasmus MC Rotterdam, NL 
 
 
Prof. dr. J. Jeekel 
Prof. dr. G.J. Kleinrensink 
Prof. dr. J.F. Lange 
Prof. Dr. P.J. Tanis 
Dr. E.B. Deerenberg 
Dr. M.M. Poelman 
S. van Egmond 
R. van den Berg 
 
 

 
 
LTFU-STITCH trial 
 
 
 
PROTOCOL TITLE  
Suture techniques to reduce the incidence of the incisional hernia, the long-term follow-up of the 
STITCH trial.  
Protocol ID 
Not yet available 
Short title 
LTFU-STITCH trial  
EudraCT number  
Not applicable 
Version 
1.5 
Date 
29th of September 2022 
Coordinating investigator 
Sarah van Egmond, BSc  
Franciscus Gasthuis & Vlietland  
Kleiweg 500, 3045 PM Rotterdam 
Erasmus MC, University Medical Center Rotterdam 
Doctor Molewaterplein 40, 3015 GD Rotterdam 
Department of Surgery 
s.vanegmond.1@erasmusmc.nl, S.Egmond@franciscus.nl 
+31 6 21 23 52 50 
Principal investigator(s) (in Dutch: 
hoofdonderzoeker/ uitvoerder) 
 
 
 
 
 
Prof. dr. P.J. Tanis 
Erasmus MC, University Medical Center Rotterdam, the 
Netherlands 
Department of Surgery 
Doctor Molewaterplein 40, 3015 GD Rotterdam 
p.tanis@erasmusmc.nl 
0031 6 29 65 91 87 
Multicenter research: per site 
 
 
Franciscus Gasthuis & Vlietland  
Dr. E.B. Deerenberg 
Email: E.Deerenberg@franciscus.nl  
3045 PM Rotterdam 
 
Elisabeth-TweeSteden ziekenhuis  
Dr. J. Heisterkamp 
 
Rijnstate  
Dr. F.J. Berends  
 
Spaarne Gasthuis 
Dr. H.B. Stockmann  
 

 
 
LTFU-STITCH trial 
 
 
 
Meander Medisch Centrum  
Prof. dr. E.C.J. Consten 
 
Rode Kruis Ziekenhuis 
Dr. H.A. Cense 
Study coordinators 
S. van Egmond 
Erasmus MC, Rotterdam, The Netherlands 
s.vanegmond.1@erasmusmc.nl 
+31 6 21 23 52 50 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
Franciscus Gasthuis & Vlietland  
Kleiweg 500, 3045 PM Rotterdam 
Department of Surgery  
Subsidising party 
Not applicable 
 
Independent expert(s) 
Not applicable  
 
 
Laboratory sites  
Not applicable 
 
 
Pharmacy  
Not applicable 
 
 

 
 
LTFU-STITCH trial 
 
 
 
PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor of legal representive 
Erasmus MC, University Medical Center 
Head of Department of Surgery: 
Prof. dr. J.M. Hendriks, surgeon   
 
 
Principal Investigator: 
Prof. dr. P.J. Tanis, surgeon 
Erasmus MC, Rotterdam, the Netherlands  
 
 
 
 

 
 
LTFU-STITCH trial 
 
 
 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE ................................................................................ 10 
2. 
OBJECTIVES .................................................................................................................... 12 
3. 
STUDY DESIGN ............................................................................................................... 13 
4. 
STUDY POPULATION...................................................................................................... 14 
4.1 
Population (base)....................................................................................................... 14 
4.2 
Inclusion criteria ......................................................................................................... 14 
4.3 
Exclusion criteria........................................................................................................ 14 
4.4 
Sample size calculation ............................................................................................. 14 
5. 
TREATMENT OF SUBJECTS .......................................................................................... 15 
5.1 
Investigational product/treatment .............................................................................. 15 
5.2 
Use of co-intervention ................................................................................................ 15 
5.3 
Escape medication .................................................................................................... 15 
Not applicable. This study will not use any escape medication. ............................................. 15 
6. 
INVESTIGATIONAL PRODUCT ....................................................................................... 16 
6.1 
Name and description of investigational product ...................................................... 16 
6.2 
Summary of findings from non-clinical studies.......................................................... 16 
6.3 
Summary of findings from clinical studies ................................................................. 16 
6.4 
Summary of known and potential risks and benefits ................................................ 17 
6.5 
Description and justification of route of administration and dosage ......................... 17 
6.6 
Dosages, dosage modifications and method of administration ................................ 17 
6.7 
Preparation and labelling of Investigational Medicinal Product ................................ 17 
6.8 
Drug accountability .................................................................................................... 17 
7. 
NON-INVESTIGATIONAL PRODUCT ............................................................................. 19 
7.1 
Name and description of non-investigational product(s) .......................................... 19 
7.2 
Summary of findings from non-clinical studies.......................................................... 19 
7.3 
Summary of findings from clinical studies ................................................................. 19 
7.4 
Summary of known and potential and benefits ......................................................... 19 
7.5 
Description and justification of route of administration and dosage ......................... 19 
7.6 
Dosages, dosage modifications and method of administration ................................ 19 
7.7 
Preparation and labelling of Non Investigational Medicinal Product ........................ 19 
7.8 
Drug accountability .................................................................................................... 19 
8. 
METHODS ........................................................................................................................ 20 
8.1 
Study parameters/endpoints ..................................................................................... 20 
8.1.1 
Main study parameter/endpoint ......................................................................... 20 
8.1.2 
Secondary study parameters/endpoints ............................................................ 20 
8.1.3 
Other study parameters ..................................................................................... 20 
8.2 
Randomisation, blinding and treatment allocation .................................................... 21 
8.3 
Study procedure ........................................................................................................ 21 
8.4 
Withdrawal of individual subjects .............................................................................. 22 
8.4.1 
Specific criteria for withdrawal ........................................................................... 22 
8.5 
Replacement of individual subjects after withdrawal ................................................ 23 

 
 
LTFU-STITCH trial 
 
 
 
8.6 
Follow-up of subjects withdrawn from treatment ...................................................... 23 
8.7 
Premature termination of the study ........................................................................... 23 
9. 
SAFETY REPORTING...................................................................................................... 24 
9.1 
Temporary halt for reasons of subject safety ............................................................ 24 
9.2 
AEs, SAEs and SUSARs ........................................................................................... 24 
9.2.1 
Adverse events (AEs)......................................................................................... 24 
9.2.2 
Serious adverse events (SAEs) ......................................................................... 24 
9.2.3 
Suspected unexpected serious adverse reactions (SUSARs) .......................... 25 
9.3 
Annual safety report .................................................................................................. 25 
9.4 
Follow-up of adverse events ..................................................................................... 25 
9.5 
Data Safety Monitoring Board (DSMB) / Safety Committee ..................................... 25 
10. 
STATISTICAL ANALYSIS ............................................................................................. 26 
10.1 Primary study parameter(s) ....................................................................................... 26 
10.2 Secondary study parameter(s) .................................................................................. 26 
10.3 Other study parameters ............................................................................................. 26 
10.4 Interim analysis (if applicable) ................................................................................... 27 
11. 
ETHICAL CONSIDERATIONS ..................................................................................... 28 
11.1 Regulation statement ................................................................................................. 28 
11.2 Recruitment and consent........................................................................................... 28 
11.3 Objection by minors or incapacitated subjects.......................................................... 28 
11.4 Benefits and risks assessment, group relatedness .................................................. 28 
11.5 Compensation for injury............................................................................................. 28 
11.6 Incentives ................................................................................................................... 28 
12. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION .......................... 29 
12.1 Handling and storage of data and documents .......................................................... 29 
12.2 Monitoring and Quality Assurance ............................................................................ 29 
12.3 Amendments .............................................................................................................. 29 
12.4 Annual progress report .............................................................................................. 29 
12.5 Temporary halt and (prematurely) end of study report ............................................. 30 
12.6 Public disclosure and publication policy .................................................................... 30 
13. 
STRUCTURED RISK ANALYSIS ................................................................................. 31 
13.1 Potential issues of concern ....................................................................................... 31 
13.2 Synthesis ................................................................................................................... 31 
14. 
REFERENCES .............................................................................................................. 32 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
7 of 24 
LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
AE 
Adverse Event 
AR 
Adverse Reaction 
ASA 
American Society of Anesthesiologists 
AWF 
Abdominal Wall Function 
BMI 
Body Mass Index (kg/m2) 
CA 
Competent Authority 
CCMO 
 
Central Committee on Research Involving Human Subjects; in Dutch: Centrale 
Commissie Mensgebonden Onderzoek 
DSMB 
Data Safety Monitoring Board 
EudraCT European drug regulatory affairs Clinical Trials  
GDPR 
 
General Data Protection Regulation; in Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IH 
Incisional Hernia 
METC  
Medical research ethics committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
NRS 
Numeric Rating Scale 
QoL 
Quality of Life 
RCT 
Randomized Controlled Trial 
(S)AE 
(Serious) Adverse Event  
Sponsor 
The sponsor is the party that commissions the organisation or performance of 
the research, for example a pharmaceutical company, academic hospital, 
scientific organisation or investigator. A party that provides funding for a study 
but does not commission it is not regarded as the sponsor, but referred to as a 
subsidising party. 
UAVG 
Dutch Act on Implementation of the General Data Protection Regulation; in Dutch: 
Uitvoeringswet AVG 
WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
8 of 24 
SUMMARY 
 
Rationale: Incisional hernias (IH) are a frequent complication after abdominal surgery. Prevalence of 
an IH varies depending on the previous abdominal procedure but could be as high as 70% in high-risk 
patients after open surgery. To investigate different fascia closure techniques in the prevention of IHs, 
the STITCH trial (NCT01132209) was designed, a randomized controlled trial in which 560 patients 
were included between October 2009 and March 2012. They compared two different closure 
techniques for closure of a midline incision in adult patients undergoing an elective abdominal 
laparotomy. Patients were randomly assigned to the intervention group (small bites 5 mm x 5 mm) or 
the control group (large bites 1 cm x 1 cm). It showed that small bites are much more effective than 
large bites in the prevention of an incisional hernia when closing a midline incision.  
So far, it has not been studied whether there is still a long-term difference in incidence of incisional 
hernia between the small bites and the large bites group. 
Objective: The primary objective of this study is to determine the difference in incidence of IH 
between the small bites and the large bites group after 10 years of follow-up from time of 
randomization in the STITCH trial. The secondary objectives are to measure quality of life (QoL), body 
image and cosmetic results, and abdominal wall function through questionnaires and physical 
examination in those patients who are still alive. 
Study design: Assessment of long-term follow-up (10-13 years) of a randomized controlled 
multicenter study based on retrospective review of patient files and relevant imaging of the entire trial 
population, as well as questionnaires and physical and radiological examination of patient who are still 
alive.  
Study population: Of the 560 included patients in the original STITCH trial, 545 completed the 1-year 
follow-up.  
Intervention (if applicable): Not applicable.  
Main study parameters/endpoints: The primary outcome measure is the 10-year midline incisional 
hernia rate. The primary endpoint will be determined for the 545 patients of the original intention-to-
treat population using Kaplan Meier analysis. In patients who died during follow-up, this will be 
evaluated by reviewing the available medical charts and radiological studies. CT-scans of the 
abdomen will be evaluated by the study-team. If CT imaging is not available, documented findings 
during physical examination by the relevant medical specialist will be considered. Patients being still 
alive with written informed consent to be contacted will be approached for their willingness to 
participate in this follow-up study, and after consent, we will reassess CT scans for an incisional 
hernia. All patients who are still alive and want to participate in this study will be asked to visit the 
hospital once for physical examination and an ultrasound of the abdominal wall. 
Secondary outcome parameters include QoL and cosmetic outcome, Patients still alive with consent 
for participation will be sent the following questionnaires: MOS SF-36 and EQ-5D (QoL), Dresden 
Body Image Questionnaire (body image), Body Image Questionnaire (cosmesis), Hernia-Related 
Quality of Life Survey (abdominal wall function). Furthermore, readmission and surgical intervention 
rates related to midline IH will be determined for the entire study population. 
Nature and extent of the burden and risks associated with participation, benefit and group 
relatedness: Undergoing an ultrasound, physical examination and completing several questionnaires 
may be considered burdensome for the patient. 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
9 of 24 
1. INTRODUCTION AND RATIONALE 
 
Incisional hernias are a frequent complication after abdominal surgery. According to Korenkov et al. 
the definition of an incisional hernia is: ‘’any abdominal wall gap with or without bulge in the area of a 
postoperative scar perceptible or palpable by clinical examination or imaging’’(1). Prevalence of an 
incisional hernia varies depending on the previous abdominal procedure but could be as high as 70% 
in high-risk patients after open surgery (2-4). In the last decade, a total of over 84,000 patients in the 
Netherlands were diagnosed with an incisional hernia and more than 44,000 surgeries have been 
performed to repair the incisional hernia (5). 
 
An incisional hernia can become symptomatic with the need for surgical repair. Symptoms such as 
pain, incarceration and decreased abdominal wall function (AWF) can occur. In addition, an incisional 
hernia can have a major impact on body image and quality of life (QoL) (6). 
 
To investigate different fascia closure techniques in the prevention of incisional hernias, the STITCH 
trial was designed. The original STITCH study (NCT01132209), a randomized controlled trial in which 
560 patients were included between October 2009 and March 2012, compared the two different 
closure techniques for closure of a midline incision (7). Adult patients undergoing elective abdominal 
laparotomy were randomly assigned to the intervention group or the control group. In the intervention 
group, the fascia was closed with small tissue bites of 5 mm every 5 mm and in the control group with 
large tissue bites of 1 cm every 1 cm. Of the 560 included patients in the original STITCH trial, 545 
completed the 1-year follow-up. After 1-year follow-up, 21% of patients in the ''large bites'' group, the 
control group, had developed an incisional hernia versus 13% of patients in the intervention, ''small 
bites'' group. Thus, that showed that small bites are much more effective than large bites in the 
prevention of an incisional hernia when closing a midline incision (7). However, the majority of 
incisional hernias will become apparent and symptomatic in the first five years after surgery (8).  
 
So far, it has not been studied whether there is still a long-term difference in incidence of incisional 
hernia between the small bites and the large bites group. We would like to propose assessment of the 
long-term follow-up of the patients included in the original STITCH trial to determine if the small bites 
are still effective in the long-term (10 year follow-up) in preventing incisional hernia.  
 
 
 
 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
10 of 24 
2. OBJECTIVES 
 
Primary Objective:  
The primary objective of the original STITCH trial was reduction of the incidence of an incisional hernia 
after open, elective abdominal surgery. The primary objective of the present study is to determine the 
difference in incidence of incisional hernia between the intervention group and the control group of the 
original STITCH trial after 10 years of follow-up from the time of randomization,. 
 
Secondary Objectives:  
The secondary objectives of this follow-up study are to measure quality of life (QoL), body image and 
cosmetic results and abdominal wall function in those patients who are still alive. 
In addition, all information is collected regarding the abdominal wall hernia (presence, location, 
duration, size, recurrence, repair) and other abdominal wall related complications such as: open 
abdomen, enterocutaneous fistula, wound problems, burst abdomen, number of abdominal 
reoperations, number of hospital admissions (and total days) with/without development of ileus. 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
11 of 24 
STUDY DESIGN 
 
The original STITCH trial (NCT01132209) was a multicenter double-blind prospective randomized 
controlled trial who randomly assigned 560 patients between October 2009 and March 2012 in the 
intervention group (small bites) or in the control group (large bites). Ultimately, 268 patients were 
included in the intervention group and 277 patients in the control group. A total of 545 patients. 
 
This current study is a long-term (10-13 years) follow-up of the original STITCH trial.  
The flowchart below graphically depicts the process of approaching the patients who were included in 
the original STITCH trial. On the original informed consent form of the STITCH trial patients were 
asked if they agreed to being contacted for a follow-up study after completion the original trial.  
 
 
 
 
 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
12 of 24 
4. STUDY POPULATION 
4.1 
Population (base)  
All 545 patients who were included in the original STITCH trial (NCT01132209) between October 2009 
and March 2012. 
4.2 
Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet the following criteria: 
- 
Available signed informed consent form for the original STITCH trial of the patients who are 
still alive. Of the patients who have died, the medical records are reviewed.  
- 
Patients must give informed consent for the current study, the long-term follow-up of the 
STITCH trial. 
4.3 
Exclusion criteria 
A potential subject who meets the following criteria will be excluded from participation in this study: 
- 
Patients that on the original informed consent form of the STITCH trial, checked the box that 
they did not want to be approached for future follow-up studies. 
- 
Patients who withdrew their informed consent during the original STITCH trial. 
4.4 
Sample size calculation  
The original STITCH trial ended up with 545 patients completing the 1-year follow-up.  
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
13 of 24 
5. TREATMENT OF SUBJECTS 
5.1 
Investigational product/treatment 
Not applicable as this is a follow-up study of a previous RCT. The surgical treatments have already 
taken place. 
 
5.2 
Use of co-intervention  
Not applicable as no co-intervention is used in this study. 
 
5.3 
Escape medication  
Not applicable. This study will not use any escape medication.  

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
14 of 24 
6. INVESTIGATIONAL PRODUCT  
6.1 
Name and description of investigational product 
Not applicable as no investigational product is used in this study.  
 
6.2 
Summary of findings from non-clinical studies  
Not applicable as no investigational product is used in this study.  
 
6.3 
Summary of findings from clinical studies 
Not applicable as no investigational product is used in this study.  
 
6.4 
Summary of known and potential risks and benefits 
Not applicable as no investigational product is used in this study.  
 
6.5 
Description and justification of route of administration and dosage 
Not applicable as no investigational product is used in this study.  
 
6.6 
Dosages, dosage modifications and method of administration 
Not applicable as no investigational product is used in this study.  
 
6.7 
Preparation and labelling of Investigational Medicinal Product 
Not applicable as no investigational product is used in this study.  
 
 
6.8 
Drug accountability 
Not applicable as no investigational product is used in this study.  
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
15 of 24 
7. NON-INVESTIGATIONAL PRODUCT 
7.1 
Name and description of non-investigational product(s) 
Not applicable as no non-investigational product is used in this study. 
 
7.2 
Summary of findings from non-clinical studies  
Not applicable as no non-investigational product is used in this study. 
 
7.3 
Summary of findings from clinical studies 
Not applicable as no non-investigational product is used in this study. 
 
7.4 
Summary of known and potential and benefits 
Not applicable as no non-investigational product is used in this study. 
 
7.5 
Description and justification of route of administration and dosage 
Not applicable as no non-investigational product is used in this study. 
 
7.6 
Dosages, dosage modifications and method of administration 
Not applicable as no non-investigational product is used in this study. 
 
7.7 
Preparation and labelling of Non Investigational Medicinal Product  
Not applicable as no non-investigational product is used in this study. 
 
7.8 
Drug accountability 
Not applicable as no non-investigational product is used in this study. 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
16 of 24 
8. METHODS 
8.1 
Study parameters/endpoints 
8.1.1 Main study parameter/endpoint 
The primary outcome measure is the 10-year midline incisional hernia rate. The size (diameter) and 
location of the hernia will be documented. 
In patients who died during follow-up, this will be evaluated by reviewing the available medical charts 
and radiological studies. CT-scans of the abdomen will be evaluated by the study-team. If CT imaging 
is not available, documented findings during physical examination by the relevant medical specialist 
will be considered. The CT scans of patients being still alive will be reassessed for an incisional 
hernia.  
8.1.2 Secondary study parameters/endpoints  
The secondary outcomes will be measured using five validating questionnaires. Quality of Life (QoL), 
body image, cosmetic results and abdominal wall function (AWF) will be reported from all patients who 
are still alive with consent for participation. Three of the five questionnaires have also been validated 
in a Dutch version. The other two were translated from English. The following measuring instruments 
will be used for this: 
• 
Quality of Life 
o 
MOS SF-36: This questionnaire consists of 36 items. The item scores are summed to 
scale scores and transformed to a 100-point scale. A higher score indicates better health 
status(9).  
o 
EQ-5D; This questionnaire consists of a total of fourteen items. The answers can be 
converted to a total score representing the health profile(10). 
• 
Body image: Dresden Body Image Questionnaire (DBIQ); consists of 35 items and five subscales 
(11). 
• 
Cosmetic results: Body Image Questionnaire (BIQ); the questionnaire consists of ten items 
evaluating body image, cosmesis and self-confidence before and after surgery. The higher the 
score in the first five items, the lower the body image. The lower the score in items 6, 7 and 8, the 
lower cosmesis assessment. The last two items are about self-confidence before and after surgery 
where 1 is ''not very confident'' and 10 is ''very confident.'' (12). 
• 
AWF: Hernia-Related Quality of Life Survey (HerQLes); this questionnaire consists of twelve 
statements where the patient can choose from six options, how much they agree or disagree with 
the statement. The higher the score, the greater the burden of the abdominal wall(13). 
8.1.3 Other study parameters  
Demographic characteristics collected during randomization during the original trial are used for follow-
up. This includes gender, age, length and weight (BMI), smoking history (yes or no), medical history 
and ASA class. 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
17 of 24 
8.2 
Randomisation, blinding and treatment allocation 
Not applicable as no additional randomisation or blinding will be performed in this study. Patients had 
already been randomized at the time they were included in the original RCT. 
 
8.3 
Study procedure 
Of patients still alive who want to participate in the follow-up study and patients who have died, the 
medical record and any available radiological imaging are reviewed retrospectively by members of the 
study team.  
All patients who are still alive and want to participate in this study will be asked to visit the hospital 
once for physical examination and an ultrasound of the abdominal wall. Subsequently, all those 
patients will be asked to complete five validated questionnaires related to quality of life, cosmesis, 
body image and abdominal wall function. There is no set time after randomization in the original 
STITCH trial when the questionnaires should be completed. Indeed, this would mean that data 
collection would have to spread out over a few years which is not desirable. 
After the physical examination and ultrasound are performed, the patient is given a brief explanation of 
the five questionnaires to be completed. The patient can choose whether to complete these 
questionnaires digitally at home or on paper at home (and return them free of charge).  
 
8.4 
Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without any 
consequences. 
8.4.1 Specific criteria for withdrawal  
Patients can withdraw their consent at any time during the study without having to give reason.  
 
8.5 
Replacement of individual subjects after withdrawal 
Not applicable, all patients are already asked to participate so substitution is not possible when they 
withdraw their informed consent. 
8.6 
Follow-up of subjects withdrawn from treatment 
Not applicable as patients do not receive treatment.  
 
8.7 Premature termination of the study 
Not applicable, the study will not be terminated prematurely. 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
18 of 24 
9. SAFETY REPORTING 
9.1 
Temporary halt for reasons of subject safety 
In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the study if there is 
sufficient ground that continuation of the study will jeopardise subject health or safety. The sponsor will 
notify the accredited METC without undue delay of a temporary halt including the reason for such an 
action. The study will be suspended pending a further positive decision by the accredited METC. The 
investigator will take care that all subjects are kept informed. 
 
9.2 
AEs, SAEs and SUSARs 
9.2.1 Adverse events (AEs) 
Not applicable, as this study does not involve an investigational medical product and this study is not 
subject to WMO.  
9.2.2 Serious adverse events (SAEs) 
Not applicable, as this study does not involve an investigational medical product. 
9.2.3 Suspected unexpected serious adverse reactions (SUSARs) 
Not applicable, as this study does not involve an investigational medical product. 
 
9.3 
Annual safety report 
Not applicable, as this study does not involve an investigational medical product. 
 
9.4 
Follow-up of adverse events 
Not applicable, as this study does not involve an investigational medical product. 
 
9.5 
Data Safety Monitoring Board (DSMB) / Safety Committee 
Not applicable, since this follow-up study has a retrospective character. 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
19 of 24 
10. STATISTICAL ANALYSIS 
10.1 Primary study parameter(s) 
We will analyse the primary outcome for the 545 patients using Kaplan Meier analysis and log-rank 
test to compare the two trial groups based on an intention-to-treat basis (7). Statistical analyses will be 
performed using IBM® SPSS® Statistics Version 29. In the case of missing data, a regression model 
is used to estimate the missing values. 
 
10.2 Secondary study parameter(s)  
Statistical comparison of quality of life, body image, cosmetic results and abdominal wall function 
between patient groups (small vs large bites technique and with or without incisional hernia) will be 
done by multilevel analysis (linear mixed-effects model with random effect for each patient) (7).  
 
10.3 Other study parameters 
Demographics and baseline characteristics will be reported using descriptive statistics. 
 
10.4 Interim analysis (if applicable) 
Not applicable, since no interim analysis is performed.  

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
20 of 24 
11. ETHICAL CONSIDERATIONS 
11.1 Regulation statement 
This study will be conducted in accordance with the principles of the Declaration of Helsinki (64th 
World Medical Association General Assembly, Fortaleza, Brazil, October 2013)  This study has been 
exempted by the medical research ethics committee (MREC); in Dutch: Medisch Ethische Toetsings 
Commissie (METC). Following review of the protocol, the MREC concluded that this study is not 
subject to the Medical Research Involving Human Subjects Act (WMO). They concluded that the study 
is a medical/scientific research, but no patients are subjected to procedures or are required to follow 
rules of behavior. 
 
11.2 Recruitment and consent 
Patients who were included in the original STITCH trial and who are still alive will be approached by 
the  study coordinator or the surgeon from the hospital they were included at the time, for participation 
in the follow-up study. Patients will only be approached if they have not checked the box on the 
Informed Consent Form of the original STITCH trial that they do not wish to be approached in the 
future for follow-up studies. Patients who indicated they had no objection to being approached will be 
contacted by telephone for participation and explanation of the study. If the patient approves, we will 
then send a subject information sheet with an informed consent form that allows the patient to make a 
well-informed and well-considered decision whether or not to participate in this follow-up study. The 
informed consent form can be returned free of charge by the patient when participation. 
 
11.3 Objection by minors or incapacitated subjects  
Not applicable as no minors or incapacitated subjects are included in this study. 
 
11.4 Benefits and risks assessment, group relatedness 
Undergoing an ultrasound, physical examination and completing several questionnaires may be 
considered burdensome for the patient. 
 
11.5 Compensation for injury 
As the study is not subject to the Medical Research Involving Human Subjects Act (WMO), the 
statutory obligation to provide insurance for subjects participating in medical research (article 7 of the 
WMO) also does not apply’. 
11.6 Incentives  
Patients will not receive any special incentives or additional treatment through participating in the 
study. Travel costs can be reimbursed. 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
21 of 24 
12. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
12.1 Handling and storage of data and documents 
Research data will be stored in a Castor database and will be handled confidentially. Data will be 
coded with e.g. A01, A02, B01, etc (the letter depends on the site of the inclusion). Research data that 
can be traced to individual persons can only be viewed by authorized personnel. These persons are 
members of the research team, members of the health care inspection, and members of the Medical 
Research Ethics Committee. Data review may be necessary in order to ensure the reliability and 
quality of the research. The handling of personal data should comply with the EU General Data 
Protection Regulation and the Dutch Act on Implementation of the General Data Protection 
Regulation. (in Dutch: Uitvoeringswet AVG, UAVG). Data will be stored at least 15 years after date of 
publication. 
 
12.2 Monitoring and Quality Assurance  
The principal investigator, a project leader, or an independent person will monitor quality of the data in 
the database by checking correctness and completeness of data for a random selection of 10% of 
patients, with a minimum of 10 patients per participating hospital. Data regarding disease, disease 
severity, treatment, and outcome will be checked. 
 
12.3 Amendments  
Amendments are changes made to the research after a favourable opinion by the accredited METC 
has been given. All amendments will be notified to the METC that gave a favourable opinion. 
12.4 Annual progress report 
Not applicable, as this study will not be subject to the Medical Research Involving Human Subjects Act 
(WMO). 
12.5 Temporary halt and (prematurely) end of study report 
The investigator will notify the accredited METC of the end of the study within a period of 8 weeks. The 
end of the study is defined as the last patient’s last visit. 
 
The sponsor will notify the METC immediately of a temporary halt of the study, including the reason of 
such an action.  
    
In case the study is ended prematurely, the sponsor will notify the accredited METC within 15 days, 
including the reasons for the premature termination. Within one year after the end of the study, the 
investigator/sponsor will submit a final study report with the results of the study, including any 
publications/abstracts of the study, to the accredited METC. 
 
12.6 Public disclosure and publication policy 
The publication policy of CCMO will be maintained. This statement contains the basic principles on 
CCMO’s position on the disclosure/ publication of research results obtained from subjects involving 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
22 of 24 
human subjects. It is the opinion of CCMO that the results of scientific research involving human 
subjects must be disclosed unreservedly. 
 
Authors of potential publications following the present study will be determined by measure of 
contribution to the study protocol, study execution and manuscript synthesis, where the final decision 
of authorship is made by the Principal Investigator. 
 
For publication of this follow-up study, the STROBE guideline will be followed (14). 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
23 of 24 
13. STRUCTURED RISK ANALYSIS  
13.1 Potential issues of concern 
Not applicable, as this study does not involve an investigational or non-investigational product. 
a. Level of knowledge about mechanism of action 
Not applicable 
 
b. Previous exposure of human beings with the test product(s) and/or products with a similar 
biological mechanism 
Not applicable 
 
c. Can the primary or secondary mechanism be induced in animals and/or in ex-vivo human cell 
material? 
Not applicable 
 
d. Selectivity of the mechanism to target tissue in animals and/or human beings 
Not applicable 
 
e. Analysis of potential effect 
Not applicable 
 
f. Pharmacokinetic considerations 
Not applicable 
 
g. Study population 
Not applicable 
 
h. Interaction with other products 
Not applicable 
 
i. Predictability of effect 
Not applicable 
 
j. Can effects be managed? 
Not applicable 
 
13.2 Synthesis 
Not applicable, as this study does not involve an investigational or non-investigational product. 
 
 
 
 

 
 
LTFU-STITCH trial 
Version 1.5, 29th of September 2022 
 
24 of 24 
14. REFERENCES 
 
1. Korenkov M, Neugebauer E. Comments on the letter from S. Petersen and K. Ludwig 
concerning our paper "Classification and surgical treatment of the incisional hernia. Results 
of expert meeting." Langenbeck's Arch Surg 386:65-73. Langenbecks Arch Surg. 
2001;386(4):310-1. 
2. Alnassar S, Bawahab M, Abdoh A, Guzman R, Al Tuwaijiri T, Louridas G. Incisional hernia 
postrepair of abdominal aortic occlusive and aneurysmal disease: five-year incidence. 
Vascular. 2012;20(5):273-7. 
3. Borab ZM, Shakir S, Lanni MA, Tecce MG, MacDonald J, Hope WW, et al. Does 
prophylactic mesh placement in elective, midline laparotomy reduce the incidence of 
incisional hernia? A systematic review and meta-analysis. Surgery. 2017;161(4):1149-63. 
4. Muysoms FE, Antoniou SA, Bury K, Campanelli G, Conze J, Cuccurullo D, et al. 
European Hernia Society guidelines on the closure of abdominal wall incisions. Hernia. 
2015;19(1):1-24. 
5. Open data van de Nederlandse zorgautoriteit [Internet]. 2022 [cited July 13th 2022]. 
Available from: https://www.opendisdata.nl. 
6. van Ramshorst GH, Eker HH, Hop WC, Jeekel J, Lange JF. Impact of incisional hernia on 
health-related quality of life and body image: a prospective cohort study. Am J Surg. 
2012;204(2):144-50. 
7. Deerenberg EB, Harlaar JJ, Steyerberg EW, Lont HE, van Doorn HC, Heisterkamp J, et 
al. Small bites versus large bites for closure of abdominal midline incisions (STITCH): a 
double-blind, multicentre, randomised controlled trial. Lancet. 2015;386(10000):1254-60. 
8. Jensen KK, Krarup PM, Scheike T, Jorgensen LN, Mynster T. Incisional hernias after 
open versus laparoscopic surgery for colonic cancer: a nationwide cohort study. Surg 
Endosc. 2016;30(10):4469-79. 
9. MOS SF-36: Meetinstrumenten in de zorg; 2012 [Available from: 
https://meetinstrumentenzorg.nl/wp-content/uploads/instrumenten/SF-36-RAND-36-
meetinstr.pdf. 
10. Group E. EQ-5D - Gezondheidsvragenlijst 1990 [Available from: 
http://gertrudpijnenburg.nl/wp-content/uploads/2019/11/Gezondheid-vragenlijst-EQ5D.pdf. 
11. Scheffers M, van Duijn MAJ, Bosscher RJ, Wiersma D, Schoevers RA, van Busschbach 
JT. Psychometric properties of the Dresden Body Image Questionnaire: A multiple-group 
confirmatory factor analysis across sex and age in a Dutch non-clinical sample. PLoS One. 
2017;12(7):e0181908. 
12. Dunker MS, Stiggelbout AM, van Hogezand RA, Ringers J, Griffioen G, Bemelman WA. 
Cosmesis and body image after laparoscopic-assisted and open ileocolic resection for 
Crohn's disease. Surg Endosc. 1998;12(11):1334-40. 
13. Krpata DM, Schmotzer BJ, Flocke S, Jin J, Blatnik JA, Ermlich B, et al. Design and initial 
implementation of HerQLes: a hernia-related quality-of-life survey to assess abdominal wall 
function. J Am Coll Surg. 2012;215(5):635-42. 
14. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. 
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 
Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495-9.