Preemer Trial - Prophylactic Mesh Versus no Mesh in the Midline Emergency Laparotomy Closure for Prevention of Incisional Hernia: a Multi Center, Double-blind, Randomized Controlled Trial
Phase: NA
Conditions: Incisional Hernia, Emergency Laparotomy, Midline Laparotomy, Hernia Prevention
Sponsor: University of Oulu

 
 
 
 
 
 
PREEMER TRIAL -   
Prophylactic  mesh  versus  no  mesh  in  midline  emergency  laparotomy  closure for 
prevention of incisional hernia: a multicenter, double-blind,  randomized controlled trial   
19.1.21 Version 3.0   
   
PRINCIPAL INVESTIGATOR:  
Elisa Mäkäräinen-Uhlbäck M.D.    
(elisa.makarainen-uhlback@ppshp.fi)    
Oulu University Hospital   
 
STUDY GROUP:  
  
Tero Rautio M.D., Ph.D.   
  
  
  
Mirella Ahonen-Siirtola M.D.    
Oulu University Hospital   
Ville Sallinen M.D., Ph.D.    
Panu Mentula M.D., Ph.D.    
Matti Tolonen M.D., Ph.D.   
Ari Leppäniemi M.D., Ph.D.    
Helsinki University Hospital   
Filip Muysoms M.D., Ph.D.    
Hospital AZ Maria Middelares, Ghent, 
Belgium   
Juha Saarnio M.D., Ph.D.   
 
STATISTICIAN:  
Pasi Ohtonen MSc (pasi.ohtonen@oulu.fi)                         
Oulu University Hospital   
 
PARTICIPANTS:  
Oulu University Hospital   
  
Helsinki University Hospital, 
Meilahti    
Helsinki University Hospital, Jorvi   
  
Turku University Hospital   
  
Tampere University hospital   
  
Lahti Central Hospital   
  
  
   
 
 
FINANCE:    
  
Government funding  
  
  
   
 
 
 
 
 
 
 
 
PREEMER Trial 2019   

 
 
 
PREEMER 
TRIAL 
- 
............................................................................................................................. ..................... 
1 
 
1. 
PROTOCOL 
SYNOPSIS 
................................................................................................................................... 4  2. 
INTRODUCTION................................................................................................................. ......
...................... 8   
2.1 INCISIONAL HERNIA INCIDENCE 
............................................................................................................................. ..... 8   
2.2. INCISIONAL HERNIA ETIOLOGY 
.................................................................................................................................. 8   
2.3 INCISIONAL HERNIA DEFINITION AND EVALUATION 
.................................................................................................... 9   
2.4 INCISIONAL HERNIA PREVENTION 
............................................................................................................................. 10   
3. 
STUDY 
OBJECTIVE 
............................................................................................................................. .......... 12  4. 
STUDY 
DESIGN 
............................................................................................................................. ................ 12  
5. 
COST 
ANALYSIS 
............................................................................................................................. .............. 13  
6. 
STUDY 
ENDPOINTS.............................................................................................................................
......... 13   
6.1 PRIMARY ENDPOINTS 
............................................................................................................................. .................. 
13   
6.2 SECONDARY ENDPOINTS 
............................................................................................................................. ..................
. 14   
7. STUDY 
POPULATION.......................................................................................................................
............ 14   
7.1. INCLUSION CRITERIA 
............................................................................................................................. .................. 
15   
7.2 EXCLUSION CRITERIA 
............................................................................................................................. .................. 
15   
8. 
CENTER 
AND 
SURGEON 
SELECTION 
.......................................................................................................... 16  9. RISK ANALYSIS 
............................................................................................................................. ............... 16   
9.1. POTENTIAL RISKS 
............................................................................................................................. ..................
..... 16   
9.2. POTENTIAL BENEFITS 
............................................................................................................................. .................. 

16   
10. STUDY METHODS 
...................................................................................................................................... 17   
10.1. ETHICS COMMITTEE APPROVAL 
............................................................................................................................  17   
10.2. STUDY DURATION AND ENROLLMENT 
...................................................................................................................  17   
10.3. STUDY PLAN 
............................................................................................................................. ..................
........... 17   
10. DATA COLLECTION 
................................................................................................................................... 17   
10.1 PATIENT INFORMED CONSENT 
............................................................................................................................. ... 18   
10.2 DATA COLLECTION 
....................................................................................................................................... ........
.. 18   
Baseline 
............................................................................................................................. ..............
.......................... 18   
Operative Procedure 
...........................................................................................................................................
.... 19   
Primary hospital stay and Discharge 
......................................................................................................................  19   
30 days visit 
............................................................................................................................. ..............
................... 20   
2 years Visit 
...........................................................................................................................................
................... 20   
5 years 
visit........................................................................................................................ .............
.......................... 21   
10.3 
BLINDING............................................................................................................................. ....
............................... 21   
11. DEFINITIONS 
............................................................................................................................. ................. 
21  11.1 DEFINITION OF INCISIONAL HERNIA 
....................................................................................................................... 21   
11.2 COMPREHENSIVE COMPLICATION INDEX 
................................................................................................................  23   
11.3 DEFINITION OF INFECTION 
............................................................................................................................. ........ 23   
11.4 ACTIVITIES ASSESSMENT SCALE 
.............................................................................................................................. 23   
11.5 PROMIS QUESTIONNAIRE 
............................................................................................................................. ........... 24   
12. SCHEDULE OF EVENTS 
.............................................................................................................................. 25   13. 
SUBJECT WITHDRAWAL AND DISCONTINUATION 

................................................................................ 26  13.1 SUBJECT LOST TO FOLLOW-
UP ............................................................................................................................. ... 26   
 
PREEMER TRIAL   2   

 
 
 
14 PROCEDURES 
............................................................................................................................. ................. 
26   
14.1. PERIOPERATIVE CARE 
............................................................................................................................................ 
27   
14.2 WOUND CLOSURE TECHNIQUE 
............................................................................................................................. .. 27   
14.3 POSTOPERATIVE TREATMENT 
............................................................................................................................... .. 28   
14.4. MESH (PROGRIPTM, MEDTRONIC) 
..........................................................................................................................  28   
15.GENERAL 
REPORTING 
REQUIREMENTS 
................................................................................................... 28  16. INVESTIGATOR’S 
RESPONSIBILITIES AND QUALIFICATIONS ................................................................ 28   
16.1 GENERAL RESPONSIBILITIES 
............................................................................................................................. ....... 28   
17 DATA HANDLING AND RECORD KEEPING 
............................................................................................... 29  17.1 CONFIDENTIALITY 
............................................................................................................................. ..................... 
29   
17.2 DATA MANAGEMENT 
............................................................................................................................................. 29   
18. CASE REPORT FORMS 
............................................................................................................................. ... 29  19. 
SAMPLE SIZE AND STATISTICAL ANALYSIS 
............................................................................................ 30  19.1 SAMPLE SIZE 
............................................................................................................................. .....................
......... 30   
19.2 ALLOCATION 
..................................................................................................................................................
........ 30   
19.3 ENDPOINT ANALYSIS 
............................................................................................................................. .................. 
30   
20. PUBLICATION POLICY 
............................................................................................................................. . 31  20.1. 
PUBLICATION PLAN 
............................................................................................................................. .....................
.. 32   
21. REFERENCES 
.............................................................................................................................................. 
32   
(   

  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL   3   

 
 
 
1. Protocol Synopsis   
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL   4   
Title   
PREEMER TRIAL - Prophylactic mesh versus no mesh in midline
emergency  laparotomy closure for prevention of incisional hernia: a
multicenter, double- blind, randomized controlled trial   
Light weight synthetic mesh for incisional hernia prevention 
after  emergency laparotomy   
Principal   
Investigator   
Elisa Mäkäräinen-Uhlbäck M.D. Oulu University Hospital   
Study Group    
Tero Rautio M.D. Ph.D. Oulu University Hospital   
Mirella Ahonen-Siirtola M.D. Oulu University Hospital   
Ville Sallinen M.D., Ph.D. Helsinki University Hospital   
Panu Mentula M.D., Ph.D. Helsinki University Hospital   
Matti Tolonen M.D., Ph.D. Helsinki University Hospital   
Ari Leppäniemi M.D., Ph.D. Helsinki University Hospital   
Filip Muysoms M.D., Ph.D. Hospital AZ Maria Middelares, Ghent, 
Belgium  Juha Saarnio M.D., Ph.D. Oulu University Hospital   
Patients, who have an emergency midline laparotomy for any   
gastrointestinal reason, will be randomized in a 1:1 ratio either to 
mesh   
group with a retrorectal prophylactic self-gripping mesh or to 
control   
group with 4:1 small stitch closure by continuous monofilament 
suture.   
Study Objective   Compare light weight synthetic prophylactic mesh to no mesh in 
midline   
emergency surgery laparotomy closure for prevention of incisional 
hernia    
Study Design   
Randomized, double-blinded, multi-center study   
Study Endpoints   
Primary Endpoint:    
Incidence of incisional hernia, either symptomatic or 
asymptomatic  detected clinically and/or radiologically within 2 
years from surgery.   
Secondary Endpoints:   
•    Comprehensive Complication Index  within 30 days from 
surgery   
•    Surgical site infection (SSI) rate defined by CDC 
classification of   
surgical site infection within 30 days follow-up   
•    Fascial rupture within 30 days from surgery   
•    Incidence of Incisional hernia within 5 years follow-up   
Study Population   

 
 
 
 

•    Incisional hernia repair rate within 2 and 5 years after 
surgery   
•    Re-operations due to mesh- or hernia within 2 and 5 years 
from   
surgery   
•    Quality of life (RAND-36, AAS, PROMIS) within 30 days, 2 
and 5   
years from surgery   
•    Medico-economic explorative measures   
o   Time to create the retrorectal space and insert the 
mesh    
o   Length of stay   
o   Costs of materials used to close the abdomen   
o   Length of sick leave   
At least 244 subjects will be enrolled in this study (122 per group, 
including   
20% off lost to follow-up during 2 years interval).   
All patients undergoing midline emergency laparotomy during the   
enrollment period will be screened for inclusion and exclusion criteria 
and   
recorded at study sites in order to identify any selection bias.   
Randomization   
Patients having emergency midline laparotomy for any 
gastrointestinal   
indication and fulfilling the inclusion criteria, will be randomized 
prior to   
surgery after giving informed consent to the study.   
Patients are randomly allocated (1:1 ratio) either to an intervention 
group   
or a control group according to a computer-generated list compiled 
by a   
biostatistician otherwise uninvolved in the clinical care of trial 
patients.   
Allocation will be stratified according to BMI (<30 and ≥30kg/m2), 
history   
of previous midline laparotomy and age (<65 and ≥65- years) and 
blocked   
within strata using random permuted blocks (block size 2, 4, 6 and 
8). A   
separate randomization list will be created for each participating 
center.   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL   5   
Total Study  
Duration   
Approximately 7-8 years:   
•    Site start-up: 3 months   
•    Study Enrollment: 24 months    
•    Short term follow-up: Discharge, 30 
days   
•    Long term follow-up: 2 years and 5 
years    
Inclusion/   
Exclusion 
Criteria   
Study Inclusion:   
•    Midline emergency laparotomy for any gastrointestinal 
indication   
Study Exclusion:   
Number of  
Patients   

 
 
 
 
•    Previous ventral hernia repair with mesh in the midline   
o   Previous inguinal or femoral hernia repair by any 
technique   
with mesh is accepted   
•    Previous WHO class of physical activity 3-4 (WHO 3 more than 
50%   
of time at rest, WHO 4 stays at rest most of the time)   
•    Relaparotomy   
•    Indication for laparotomy is incarcerated hernia   
•    Pregnant or suspected pregnancy   
•    <18 years    
•    Metastastic malignancy of any origin   
•    Planned ostomy   
•    Patients living geographically distant and/or unwilling to return 
for   
follow-ups    
•    No informed consent   
•    Subject participates in another RCT   
Intra-operative exclusion criteria applicable for both randomization 
groups   
•    Abdomen is left open   
•    Second look laparotomy planned   
•    Inability to keep the mesh securely out of the peritoneal 
cavity or   
close the anterior fascia   
•    Intra-abdominal malignancy diagnosed at the operation   
•    >2 cm hernia in midline   
•    Ostomy made at the operation   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL   6   
Human 
Subjects  
Protection   
Full approval of Ethical Committee of Oulu University Hospital 
approved by  Institutional revision board in each participating hospital, 
with all other   
specific approvals, must be obtained for the study prior to study 
initiation  at the site. Subjects must sign an EC-approved Informed 
Consent Form   
(ICF) prior to enrollment into this study.   
As the previous research on synthetic mesh utilized as prophylaxis 
at   
emergency laparotomies is scarce, an analysis of the complications 
and   
risks will be evaluated for safety reasons after 30 patients have 
been   
randomized to both groups and reached 30 days follow-up. For the 
same   
reason, there will be further analysis on the complications of the 
mesh   

 
 
 
 
after 30 patients randomized to each group have reached the 2 
years  follow-up.   
Data Collected    Data collected will include the following:   
•    Demographics, Patient Characteristics, and Pre-operative 
History:   
Age, BMI, previous surgical history, comorbid conditions 
and   
medications, history of smoking, previous hernias and 
hernia   
related operations   
•    Intra-Operative Assessment: Prophylactic antibiotics, ASA,   
presence of hernias in midline, rectus diastasis, operative 
time,   
blood loss, contamination class, surgical procedure, ostomy   
creation and its’ location from midline, length of wound, length 
and   
type of suture materials used, drains, vacuum assisted closure,
other temporary closure method used, skin closure.   
•    Post-Operative Assessment through Discharge: Surgical site   
infections, complications, re-operations, pain score (VAS) at   
discharge, Quality of life questionnaire, seromas, burst 
abdomen,   
fascial dehiscence, length of stay, mesh removals, 
length of   
planned sick leave, place of discharge.   
•    Follow-Up Assessments: complications, clinically and/or   
radiologically detected hernia rate, procedure- or incisional 
hernia-  
related readmissions, procedure- or incisional hernia 
related   
reoperations, QoL (RAND-36, AAS, PROMIS) and 
economic   
measures, pain of abdominal wall, long-term seromas.    
Data will be collected 2 and 5 years postoperatively.    

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL   7   
Data collection   
Primary data collection will be performed by participating surgeons 
using   
electronical database.   
Statistical 
Analysis    
All analyses will be performed by or under the guidance of 
professional   
statistician and following the CONSORT guidelines.   
The primary endpoint as well as other categorical data will analysed 
by χ2-   
test or Fisher’s exact test. Ninety-five % confidence intervals (95% CI)
are   
presented for between group differences (effect sizes). The incidence 
of   
hernia will also be analyzed using Kaplan-Meier analysis. Student’s t-
test or   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
2. 
Introduction   
 
2.1 Incisional hernia incidence    
Incisional hernia (IH) is a common complication of abdominal wall surgery. Its’ incidence 
varies  greatly (2–30 %) among studies (1-3) . The incisional hernia incidence is 
influenced by several  factors, such as closing technique (4,5) , follow-up time (6)  and 
the modality of radiological  investigations,(7,8) , patient characteristics and co-
morbidities as well as indication and type for  surgery(9).   
 
 
 2.2. Incisional hernia etiology   
The etiology of incisional hernia is multimodal. The site and orientation of the incision 
has an  influence on the IH rates. Non-midline incisions—both paramedian and 
transverse—carry a  significantly reduced risk of IHs compared to midline incisions (10-
11) . Suturing technique and  the suture material used affect the hernia rate as well. 
Taking small bites of 5 mm with an  intersuturing space of 5 mm with slowly 
absorbable monofilament suture results in a lower  hernia incidence compared to large 
bite mass suturing  (4-5, 12-14) .   
 
There is lack of evidence of basic biological pathogenesis of incisional hernias (IH). 
Specific  features of connective tissue and the quality of fibroblasts are proposed to have 
an influence  on the risk for hernia formation (15). The inflammatory response after an 
incision results in the  fibroproliferative phase. Incisional hernia may be a result of 
disturbation in the fibroblast  proliferation in the laparotomy wound matrix (16).    
 
Welch test will be used for continuous variable, the latter if 
assumption of  homogenous variances does not hold.    
Linear mixed model (LMM) or generalized linear mixed model 
(GLMM) will  be used for repeatedly measured data, the previous for 
continuous data   
and latter for categorical data.   
Finance  
   
Materials and visits are funded by hospital districts as part of 
treatment   
expenses. External funding will be applied to cover the costs 
caused by   
imaging.    

PREEMER TRIAL   8   

 
 
Fascial ischemia is presumed to be one crucial factor in the development of an IH. The 
fascia is  hypovascular and a wound experiences hypoxic stress immediately after 
surgical incision, which  has been considered a major risk factor for wound failure. 
Hypoxia interferes with angiogenesis  and 
the 
healing 
process 
(17). 
The 
revascularization at the wound site is critical to improve  healing response (18). Good 
surgical skills and maintaining sufficient perfusion in the wound  area are important 
issues to be noted (19).     
 
Along  with  previously  mentioned  physiological  alterations,  patients’  comorbidities  
and  characteristics can predispose them to develop of a hernia (9) . Connective 
tissue disorders  increase the risk for herniation among various other patient-related 
factors (20, 21). One of the  most common risk factor, that increase the likelihood of 
development an IH is smoking (75 %)  (22). As a result of an analysis of 14,618 patients, 
Bosanquet in his review and meta-regression  determined  the  factors  affecting  
midline  IH  rates:  diabetes  mellitus,  obesity,  cachexia,  increasing  age,  male  sex,  
chronic  obstructive  pulmonary  disease  (COPD),  a  history  of  or  operation for an 
abdominal aortic aneurysm (AAA), anaemia, smoking, corticosteroids and  surgical 
site infection (SSI). Summarising the results of 56 publications, the prevalence of IHs  
after midline laparotomy was 12.8 % (range: 0 to 35.6 %) with a mean follow-up time 
23.7  months (21) .   
 
 
2.3 Incisional hernia definition and evaluation   
 
Most commonly, an IH is a bulge or a gap in the area of a postoperative scar. It 
can be  asymptomatic but is often associated with symptoms, such as pain, cosmetic 
discomfort, bowel  obstruction or even incarceration (23,24) . Valsalva’s manoeuvre is 
used to make the hernia  more apparent clinically: the increase in intra-abdominal 
pressure causes the hernia sac to  enlarge and protrude through the anatomic defect. 
The clinical examination is recommended  to be performed in both standing and supine 
positions.   
 
The examination can be difficult in obese patients or in postoperative situations in 
which  incisional hernia may be difficult to distinguish from a postoperative complication, 
such as a  hematoma,  abscess  or  seroma.  The  radiological  imaging  (ultrasound  

(US),  computed  tomography (CT) or magnetic resonance (MRI)) is useful in specifying 
the diagnosis (8,25-27) .   
 
 
 
PREEMER TRIAL   9   

 
 
A  standardised  dynamic  abdominal  sonography  for  hernias  offers  a  safe  and  a  
low-cost  diagnostic tool with great specificity and positive predictive value (28) . A CT 
scan can also be  an option in some cases like when planning operative treatment, 
although it induces a radiation  load for patients.    
 
When  evaluating  the  IH  rate,  the  difference  between  physical  examination  and  
imaging  modalities (ultrasound or computer tomography) is important in terms of 
accuracy (29,30) . A  standardised examination and dynamic evaluation by ultrasound 
of the abdominal wall is  recommended in evaluating a possible hernia (14,31).  
Incidence of IHs increases during a  follow-up study time from 12.6 % at 12 months to 
22.4 % at 36 months(6,32,33).    
 
There is a great diversity of abdominal wall IHs. During the early years of 2000 the first 
proposals  for the classification of incisional ventral hernias were published. Through 
2009, there were  several proposals for classifying IHs according to defect size, 
recurrence and topography to  some extent, but none of these achieved wide 
recognition or routine use(34-36). In 2009, the  European Hernia Society (EHS) 
published a formula to classify primary and incisional abdominal  wall hernias (36).   
 
 
2.4 Incisional hernia prevention   
 
European Hernia Society (EHS) guideline strongly recommends to utilise a non-midline 
approach to  a laparotomy whenever possible to decrease the incidence of incisional hernia 
(14). However, this  is clearly not an option in an emergency laparotomy, as midline incision 
is the fastest and the best  visualizing opening to explore the whole abdominal cavity in an 
emergency setting.    
For elective midline incisions, evidence-based recommendation is to perform a continuous 
suturing  technique with slowly absorbable monofilament suture when closing the incision 
(14) Suturation  should be done performing a single layer aponeurotic closure technique 
without separate closure  of the peritoneum. A small bites technique with a suture to wound 
length (SL/WL) ratio at least 4:1  is the current recommended method of fascial closure (12-
14, 37,38).   
 
Prophylactic mesh augmentation in a non-emergency setting appears effective and safe and 

can be  suggested for high-risk patients (39-40). However, no recommendations can be 
given on the optimal   
 
 
PREEMER TRIAL  10   

 
 
technique to close emergency laparotomy incisions because of lack of evidence (14) . This 
problem  should be emphasized on due to high rates of IH after emergency laparotomy 
(41,42). All this makes  the use of prophylactic mesh in the emergency setting an interesting 
proposition, as it may decrease  the rate of IHs. However, there are concerns over potential 
mesh related complications including  infection, chronic pain, seromas and bowel fistulas 
especially in emergency situations like peritonitis  and intestinal obstruction. There is 
preliminary evidence published about the safety and efficiency  of the prevention of IHs 
using meshes in the emergency laparotomy closure even in contaminated  conditions 
(43,44).    
 
In the resent systematic review and meta-analysis, only results of 2 studies and 
altogether 299  patients were eligible for the analysis (42) . Swiss case-control study 
reported an IH rate of 3,2%  (2/63) in the mesh group and 28,6% (20/70) in the control 
group (43) . Spanish study group had the  same kind of results in their retrospective 
cohort; IH rate of 5,9% (3/50) in the mesh group and  33,3% (33/100) in the control 
group (44) . There was no statistically significant difference in the  incidence of surgical 
site infection or other complications when prophylactic mesh group was  compared to 
standard closure group. SSI rate in Swiss study was 60% and respectively only 17% in  the 
Spanish study. This may reflect differences in the patient selection, therefore the safety 
profile  of the prophylactic mesh in the emergency setting has not been adequately 
described. Neither of  the studies included in meta-analysis were not randomized controlled 
trials. There were also many  methodological differences including patient selection, used 
mesh, and mesh placement. Thus, the  conclusion of the systematic review paper was that 
there are limited data to assess the effect or  safety of the use of prophylactic mesh in the 
emergency laparotomy setting (42) . Randomized  control trials are required to address 
this important clinical question. EHS guideline group resulted  the same conclusion in their 
recommendation report (14).   
 
There are about 1650 patients are operated in Finland because of IH every year. 
According to  the European study, the estimated cost for IH surgery is 6450 euros (45). 
The corresponding  costs in Sweden were even higher reaching 9060 euros per 
treatment (12). Extrapolated to  Finland, this means that operative treatment of IHs 
cause more than 10 million expenses to the  Finnish health care sector in a year.  
Some of these costs may be avoidable by using the  prophylactic mesh during the 

closure of midline emergency laparotomies in the patients with  IH risk factors.    
 
PREEMER TRIAL  11   

 
 
 
 
Therefore, our study group stands on the idea to design and carry out the PREEMER 
randomized  controlled trial (RCT) comparing prophylactic mesh to best standard 
suturing technique in this  challenging setting.   
 
 
 
3. Study Objective   
 
The objective of this study is to compare prospectively the feasibility and the potential 
benefits of  retrorectus self-gripping mesh (ProgripTM, Medtronic) to controls operated with 
no mesh by using  the best standard 4:1 small stitch suturing technique.    
 
 
4. Study Design   
This study is a multicenter, double-blinded, randomized controlled trial. Parameters will be   
collected prospectively after randomization. All enrolled subjects will undergo assessments 
at the  following intervals: pre-operative, operative, discharge, 30 days, 2- and 5-years 
post–surgery. A   
description of the study visits and required study procedures is summarized in Section 12,   
Schedule of events.    
 
All patients are evaluated both clinically and radiologically at 2 years after index procedure 
in   
order to diagnose clinical and/or radiological incisional hernia. The follow up will continue 
until 5  years after the surgery to assess long-term results and safety.    
 
Ultrasound with and without Valsalva maneuver will be performed to all patients 2 years 
after   
surgery. The extent of the fascial defect and hernia sac volume (ie. the volume of incisional 
hernia)  are measured and graded according to the European hernia society criteria. (46)   
 
If there is a suspicion of symptomatic or asymptomatic incisional hernia according to 
clinical   
assessment and ultrasound findings are inconclusive, CT scan is required to verify the 
diagnosis of  IH. If a patient have had no imaging done for any reason, the result of clinical 

evaluation is   
recorded. In case of several imaging modalities accomplished, all results are recorded. All 
study   
 
 
 
PREEMER TRIAL  12   

 
 
patients are guided to contact their study site in case of any suspicion of incisional hernia 
at any  point during follow up.    
 
Quality of life will be measured using RAND-36, Activities Assessment Scale (AAS) and 
PROMIS  questionnaire at all follow-up visits at 1 months, 2 years and 5 years as well as 
when a hernia is  diagnosed.   
 
5. Cost analysis    
 
Costs of the treatment    
•    Mesh and other materials used to close the abdomen   
•    Need for futher surgery and medical treatment   
o   All complications of primary surgery   
o   Mesh-related need for surgery or other treatment   
o   Hernia-related need for surgery or any help from medical system   
o   Length of sick leave   
o   Need for rehabilitation before returning to previous place of 
home   
o   Length of stay in the hospital   
for both groups will be analyzed in detail.   
 
 
6. Study Endpoints   
 
6.1 Primary Endpoints   
 
The primary endpoint of this study is the incidence of incisional hernia, either 
symptomatic or  asymptomatic detected clinically and/or radiologically within 2 years 
after surgery.   
 
In case of inconsistency between clinical and radiological evaluation exists or either one is 
missing  for any reason, a following definition of primary endpoint will be used:   
 
 
 
 
 
 
 
Primary   
endpoint   
Hernia   
Hernia   
Hernia   
Clinical   
exam result   
Imaging  
result   

PREEMER TRIAL  13   

 
 
 
 
 
 
 
 
 
 
 
 
If there is inconsistency between ultrasound and CT scan, the result of CT scan will be applied.    
 
6.2 Secondary Endpoints   
 
 
Secondary Endpoints:   
•    Comprehensive Complication Index within 30 days from surgery   
•    Surgical site infection (SSI) rate defined by CDC classification of surgical site 
infection   
within 30 days follow up   
•    Fascial rupture within 30 days from surgery   
•    Incidence of Incisional hernia within 5 years follow-up   
•    Incisional hernia repair rate within 2 and 5 years after surgery   
•    Re-operations due to mesh- or hernia within 2 and 5 years from surgery   
•    Quality of life (RAND-36, AAS, PROMIS) within 30 days, 2 and 5 years from 
surgery   
•    Medico-economic explorative measures   
o   Time to create the retrorectal space and insert the mesh    
o   Length of stay   
o   Costs of materials used to close the abdomen   
o   Length of sick leave   
 
 
7. Study Population   
Eligible patients will be recruited at the approved participating sites. All patients who are 
eligible,  meet the inclusion and none of the exclusion criteria of this study, will be offered 
enrolment into  the study at each study site. A screening log of all gastrointestinal 
emergency midline   
laparotomies during study period will be maintained for further assessment of selection biases.    
 
 
No hernia   
Hernia   
Hernia   
Hernia   
No hernia   
No hernia   
No hernia   
No hernia   
No hernia   
Hernia   
Missing   
Hernia   
No hernia   
Missing   
No hernia   
Missing   
Hernia   
Hernia   
Missing   
No hernia   
No hernia   

PREEMER TRIAL  14   

 
 
 
 
 
The following patient inclusion/exclusion criteria will be required for the study.    
 
 
7.1. Inclusion Criteria   
•    Midline emergency laparotomy for any gastrointestinal indication   
o   Conversion from laparoscopy to laparotomy is considered as inclusion criteria 
from   
Study protocol version 3.0 onwards.     
 
7.2 Exclusion Criteria   
•    Previous ventral hernia repair with mesh in the midline   
o   Previous inguinal or femoral hernia repair by any technique with mesh is accepted   
•    Previous WHO class of physical activity 3-4 (WHO 3 more than 50% of time at rest, WHO 
4   
stays at rest most of the time)   
•    Relaparotomy   
•    Indication for laparotomy is incarcerated hernia   
•    Pregnant or suspected pregnancy   
•    <18 years    
•    Metastastic malignancy of any origin   
•    Planned Ostomy   
•    Patients living geographically distant and/or unwilling to return for follow-ups    
•    No informed consent   
•    Subject participates in another RCT   
Intra-operative exclusion criteria applicable for both randomization groups   
•    Abdomen is left open   
•    Second look laparotomy planned   
•    Inability to keep the mesh securely out of the peritoneal cavity or close the anterior 
fascia   
•    Intra-abdominal malignancy diagnosed at the operation   
•    >2 cm hernia in midline   
•    Ostomy made at the operation   
 
 
 
 
 
PREEMER TRIAL  15   

 
 
 
8. Center and Surgeon Selection   
Participating investigators are qualified surgeons experienced with surgical emergency   
management of patients with emergency midline laparotomy and centers have a patient   
population large enough fitting the study requirements. All surgeons considered for 
participation  must be experienced in closing the abdomen by 4:1 small stitch technique 
and prophylactic self-  
gripping polyester mesh (Progrip TM) placement. A detailed brochure with step-by-step 
pictures of  midline laparotomy closure and mesh application will be delivered to each 
participating hospital.  Principal investigator may advice with mesh application technique if 
desired.   
 
 
Hospitals located in Finland are considered for participation.    
 
9. Risk Analysis   
 
9.1. Potential Risks   
Surgeons performing emergency laparotomies will be trained and guided for the mesh 
placement.  Based on previous studies, the use of the mesh is both safe and effective. 
Study patients will be   
followed very closely postoperatively.    
 
As the previous research on synthetic mesh utilized as prophylaxis at emergency midline   
laparotomy is scarce, an analysis of the complications and risks is done and evaluated for 
safety   
reasons after 30 patients have been randomized to each group and reached 30 days follow-
up. For  the same reason, there will be further analysis on the complications of the mesh 
after 30 patients  randomized to each group have reached the 2 years follow-up.    
If there are significantly more serious complications in either group compared to other at 30 
days  or 2 years control, the trial will be discontinued.   
 
9.2. Potential Benefits   
There may be some benefit due to trial-related closer follow-up of patients. Patients 
with a  prophylactic mesh might have a lower incisional hernia rate.    
 
 
 

 
 
 
PREEMER TRIAL  16   

 
 
 
10. Study Methods   
 
10.1. Ethics Committee Approval   
The study protocol, patient informed consent form and other required study 
documentation will  be reviewed and approved by an ethics committee in Oulu University 
hospital and any other   
required body, prior to study start-up.   
 
10.2. Study Duration and Enrollment   
Study enrolment will take approximately 24 months. The enrolled patients will have a 
short-term  follow-up at 30 days and, long-term follow-up at 2 and 5 years.    
10.3. Study Plan   
 
   
Figure 1 Flow Chart   
 
Assessing 
for 
eligibility 
All patients 
with an   
gastrointes
tinal   
emergency 
midline   
laparotomy  
 
Random
ization   
(N=24
4) 
 
 
Control 
Group  
(N=12
2)  
 
 
 
Mesh 
Grou
p 
(N=1
22) 
 
Intend 
to treat  
populat
ion   
reachin
g 
30  
days 
control  
 
Intent to 
treat   
populati
on   
reaching 
2 
years   
control  
 
Intent to 
treat   
populati
on   
reaching 
5 
years   
control  
 
 
1
0
. 
D
a
t
a 
C
o
ll
e
cti
on    
 
 
 
Intraop
erative  
exclus
ion  

 
 
Intend to treat  population   
reaching 30  days control  
 
Intent to treat   
population   
reaching 2 years   
control  
 
Intent to treat   
population   
reaching 5 years   
control  
 
 
 Intraop
erative  
exclus
ion 
Data will be collected at baseline, operative procedure, discharge, 30 days, 2 years and 
5 years.  Specific databases (Hoitoilmoitusrekisteri HILMO, Tilastokeskus) may be used 
to collect data of  patients’ survival and operations done to patient outside study sites. If 
there is any suspicion of   
 
PREEMER TRIAL  17   

 
 
incisional hernia raised at any point of the follow-up, the patient is advised to contact the 
study  site and additional clinical evaluation and ultrasonography if needed is arranged.    
The data will be collected using electronical CRFs and software designed for this study.   
 
 
10.1 Patient Informed Consent   
Using the study-specific, ethics committee approved, informed consent form, information   
pertinent to this study will be provided to the subjects and/or representative in writing and 
using  non-technical language. The consent form will include a description of the study and 
its purpose,   
potential benefits, potential risks, site contact information, and all other elements required of 
an  informed consent.   
Subjects are required to voluntarily sign the informed consent form before any study-
specific   
procedure is performed. The Investigator will conduct the informed consent process and will   
answer questions the subjects may have. If the subject agrees to participate, the informed-  
consent form must be signed and dated by the subject prior to enrolment in the study and   
separately signed and dated by the investigator taking consent. Only subjects who have 
signed the  study informed consent will be included in the study.   
 
 
10.2 Data Collection   
 
Following information of patients will be collected using electronic database. The 
patient is  pseudonymized for data collection and all data will be handled using 
study-ID.    
 
 
Baseline   
•    Age   
•    BMI   
•    Charlson Comorbidity Index   
•    Previous surgical history of 
abdomen   
•    History of smoking   
•    Previous hernias   
•    Previous hernia-related operations   
•    Previous WHO scale   

•    Medications affecting healing   
 
PREEMER TRIAL  18   

 
 
 
o   Corticosteroids   
o   Immunosupressive 
medications   
o   Biologics   
•    Creatinine   
•    INR   
 
 
Operative Procedure    
 
•    Prophylactic antibiotics   
•    ASA   
•    Presence of hernias in midline   
•    Presence and width of rectus diastasis   
•    Contamination class   
•    Surgical procedure   
•    ICD-10    
•    Loss of blood   
•    Time to create the retrorectal space and insert the mesh   
•    Length of wound   
•    Suture material and needle used   
•    Drains left   
•    Vacuum assisted closure/other temporary closure/skin left 
open  •    Skin closure   
 
Primary hospital stay and Discharge    
 
•    Surgical site infection (SSI) rate   
•    All complications during hospital stay Comprehensive Complication 
Index  •    Re-operations   
•    Burst abdomen   
•    Fascial dehiscence   
•    Length of stay (LoS)   
•    Mesh removals   
 
 
PREEMER TRIAL  19   

 
 
 
•    Place of discharge   
 
Patients are guided to contact their study site in case of any problems with their 
recovery, any  suspicion of hernia occurrence or wound complications.    
 
 
30 days visit   
 
The recovery of all patients is assessed at 30 days after the operation. All the patients are 
called   
to. If there are any deviations in recovery, patient is invited to outpatient clinic for follow-up 
visit.   
 
 
•    Date of return to previous home unit   
•    Return to previous level of activity   
•    Return to work, length of sick leave   
•    Bulging   
•    Wound status    
•    Any complications of recovery   
•    Re-admissions   
•    Re-operations   
•    Removal of mesh   
•    Quality of life (RAND-36, AAS, 
PROMIS)  •    Protocol deviations   
 
 
2 years Visit   
 
Patient related recovery outcomes and QoL questionnaires will be completed and any   
complications, clinical signs and/or abdominal ultrasound findings of incisional hernia or 
protocol  deviations will be reported. Both the patient and the surgeon assessing the 
recovery and well-  
being are blinded of the randomization group.    
 
Ultrasound findings will all be analyzed by single independent radiologist in each study 
site,   
blinded of the randomization group. Possible hernia opening, its size, location and 

incisional   
hernia sack volume will be defined both at rest and with Valsalva maneuver. If the 
findings are   
 
 
PREEMER TRIAL  20   

 
 
inconclusive or there is discrepancy between the clinical assessment and imaging or a 
patient has  a symptomatic incisional hernia and operative treatment is indicated, 
abdominal CT scan will be  done to verify the hernia diagnosis or to plan operative 
technique.     
 
 
5 years visit   
 
Patient related functional outcome and QoL shall be completed and any complications, 
clinical  signs of incisional hernia or protocol deviations are reported. Ultrasound scan will 
be done   
following the same protocol as described at 2 years control if there is any suspicion of 
incisional  hernia.    
 
 
10.3 Blinding   
Study patients will be blinded of the randomization group during the whole follow-up period. 
Both  the surgeon evaluating the outcome at 30 days, 2- and 5- years control as well as 
radiologist will   
be blinded of the randomization group. The method of fascial closure (i.e. the allocated   
procedure) will not be revealed in medical records. In both groups, the following sentence 
will be   
written in the medical records: ”Fascial closure was performed according to randomization   
group”. Patients randomization number will be available in medical records. Envelopes marked   
with randomization number containing allocated group information are accessible at all 
times in   
case of complications or other need to know the allocated group. A record of unsuccessful 
blinding  will be maintained and published.   
 
11. Definitions   
 
11.1 Definition of Incisional hernia   
 
Definition and classification by European Hernia Society of Incisional hernia will be used.   
In the European Hernia Society (EHS) IH classification the abdomen is divided into a 
midline  zone and a lateral zone. Borders for the midline area are cranially the 
xyphoid, caudally the  pubic bone and laterally the lateral margin of the rectal sheath.   
 

 
 
 
 
 
 
PREEMER TRIAL  21   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EHS classification for incisional abdominal wall hernias.  (46)   
 
Midline Incisional Hernias are divided into the following subgroups M1–M5:   
M1: subxiphoidal (from the xiphoid till 3 cm caudally)   
M2: epigastric (from 3 cm below the xiphoid till 3 cm above the umbilicus),   
M3: umbilical (from 3 cm above till 3 cm below the umbilicus),   
M4: infraumbilical (from 3 cm below the umbilicus till 3 cm above the 
pubis)  M5: suprapubic (from the pubic bone till 3 cm cranially).   
 
 
 
 
 
 
 
 
 
 
 
 
EHS classification: zones of midline hernias.   
 
 
 
 
PREEMER TRIAL  22   

 
 
 
11.2 Comprehensive Complication Index   
 
All events should be classified according to the Comprehensive Complication Index.    
 
11.3 Definition of Infection   
 
CDC definition of surgical site infection for incisional site infection will be used.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.4 Activities Assessment Scale   
 
A Finnish translation of Activities Assessment Scale will be used (47).   
 
 
 
 
 
 
 
 
 
 
PREEMER 
TRIAL  23   
Kuinka vaikeiksi 
olet  kokenut 
seuraavat   
toimet 
viimeisimmän  
vuorokauden 
(24h)   
aikana?   
Ei   
lainkaa
n  
vaikeak
si   
Jonkin   
verran   
vaikeak
si   
Melko   
vaikeak
si   
Hyvin   
vaikea
ksi   
Mahdottom
aksi   
En 
ole 
tehnyt  tätä 
viimeisen  
vuorokaud
en  aikana 
muusta   
syystä   
Paikoillaan   
makaaminen   
1   
2   
3   
4   
5   
6   
Istuminen   
1   
2   
3   
4   
5   
6   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.5 Promis 
Questionnaire    
 
Asettuminen   
makuulle/istuall
een   
1   
2   
3   
4   
5   
6   
Kurkottelu tai   
venyttely   
1   
2   
3   
4   
5   
6   
1-2 
kg 
nostaminen   
1   
2   
3   
4   
5   
6   
Sisätiloissa   
liikkuminen   
1   
2   
3   
4   
5   
6   
Portaiden 
kiipeämine   
1   
2   
3   
4   
5   
6   
Liikkuminen 
ulkona tai   
töissä   
Paikoillaan olo,   
esimerkiksi 
televisiota  tai 
tietokonetta   
katsoen, lukien 
tai   
puhelimessa 
puhuen   
1   
2   
3   
4   
5   
6   
Kevyet 
askareet,  
esimerkiksi 
kevyet  
kotityöt, 
kyläily   
1   
2   
3   
4   
5   
6   
Kohtalaisen 
raskaat  
askareet, 
esimerkiksi  
pihatyöt, 
lumityöt,   
reipas kävely, 
siivous   
1   
2   
3   
4   
5   
6   
Raskas 
fyysinen   
aktiivisuus, 
kuten   
urheilu,   
kuntosaliharjoit
telu,  painavien 
taakkojen  
nostelu, raskas 
työ   
1   
2   
3   
4   
5   
6   
Seksuaaline
n   
kanssakäymi
nen   
1   
2   
3   
4   
5   
6   
1  
2  
3  
4  
5  
6   

A Finnish translation of Promis-questionnaire will be used to evaluate the likelihood of 
incisional  hernia(48).   
 
 
PROMIS – kysely arpityräriskin arvioimiseksi   
1.  Uskotko, että Sinulla voi olla 
arpityrä?   
   Kyllä   
   Ei   
2.  Tunnetko kipua arvessa?   
 
 
PREEMER TRIAL  24   

 
 
   Kyllä   
   Ei   
3.  Onko arvessa pullotusta tai pattia?   
   Kyllä   
   Ei   
4.  Näkyykö arvessa pullostusta tai pattia?   
   Kyllä   
   Ei   
5.  Painosi?   
_____________ kg   
6.  Pituutesi?   
_____________ cm   
7.  Tupakoitko, tai oletko koskaan tupakoinut 
päivittäin?   
   Kyllä   
   Ei   
 
 
 
12. Schedule of Events   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PREEMER TRIAL  25   
Schedule of 
Events   
Baseli
n  
Discha
r  
ge   
30  
days 
+ 7  
days 
2 year  
± 30   
days  
5   
years  
± 30  
days  
Unscheduled 
Visit   
Informed Consent  
X   
   
   
   
   
   
   
Demographics and 
medical history   
X   
   
   
   
   
   
   
Risk analysis for   
hernia   
X   
   
   
   
   
   
   
QoL (RAND-36, 
AAS,   
PROMIS)   
   
   
X   
X   
X   
X   
   
e       Procedure   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Complete if applicable   
**Complete when lost to follow-up, consent withdrawal or subject has completed all study 
related  visits.   
 
 
13. Subject Withdrawal and Discontinuation   
The subject’s participation in any clinical trial is voluntary. The subject and/or the 
representative  of subject has the right to withdraw at any time without penalty or loss of 
benefit. Study   
withdrawal means the subject is no longer participating in the study and no further study-
related  follow-ups will be performed. All subjects that withdraw after informed consent is 
signed will be  evaluated at the time of withdrawal. Every effort will be made to document 
the subject outcome  at the time of withdrawal. Data collected until withdrawal will be 
analyzed. The investigator has  the right to discontinue subjects from the study at his/her 
discretion to ensure wellbeing of the   
subject. The reasons for withdrawal shall be documented (electronic Patient Withdrawal 
Request  Form).   
 
 
13.1 Subject lost to Follow-up    
The investigator will attempt to contact the subject at least three times prior to designating 
them  as lost to follow-up. The patient who may hesitate to come to follow-up visit, are 
asked to return  the PROMIS questionnaire to estimate the risk of incisional hernia (48). 
The investigator will   
document the date and type of attempted communication. If a subject cannot be reached 
during  the visit window, a missed visit will be recorded. Each patient in the trial will be 
invited for every  follow-up visit according to schedule until he/she withdraws.    
 
14 Procedures   
 
Procedure details     
X   
   
   
   
   
   
Clinical evaluation  
X   
   
X   
X   
X   
X   
X   
Ultrasound findings 
 
 
X 
(X*) 
(X)   
Protocol Deviation 
X* 
X* 
X* 
X* 
X* 
X* 
X*   
Complications 
 
X* 
X* 
X* 
X* 
X* 
X*   
Study Closure 
Form   
   
   
   
   
   
X**      

 
 
PREEMER TRIAL  26   

 
 
 
14.1. Perioperative care   
Perioperative care includes the assessment and optimization of medical risk factors and 
standard  anesthesia. Antibiotic prophylaxis is accomplished according to the hospital 
protocol and routine  practice.    
 
 
Postoperative treatment at the surgical ward is accomplished according to the standard protocol.    
 
 
14.2 Wound Closure technique   
 
At the end of the operation, the abdomen will be closed according to patient’s 
randomization  group if applicable.    
 
In the mesh group, the posterior layer of rectus sheath is opened as close to midline as 
possible   
without interrupting the midline. The space behind the rectus muscle is created mainly using 
blunt  dissection. At each ends of the incision, opening of the retrorectus space is reached 
both cranial   
and caudal over the ends of the wound, if applicable. The posterior layer is closed using 0 
or 2-0   
slowly absorbable monofilament 4:1 small stitch techinique. The stitch bites are 5 mm with 
5mm   
interstitch space. The length of the wound is measured, as well as the length of suturing 
material   
used. The aim is to close using suture material at least four times the length of the wound 
(4:1) by  small stitch technique. After securing there will be no contact with the mesh and 
abdominal   
cavity, 8 cm wide self-gripping mesh (ProgripTM, Medtronic) is applied on the posterior layer 
of the  rectus sheath, reaching over the opening at each end. The anterior layer of rectus 
sheath is closed  using slowly absorbable monofilament USP 2-0 or 0 suture by 4:1 small 
stitch technique. The   
length of the mesh and suture material used are measured. Subcutaneous layer will be left 
open if  contamination class is 4. The subcutaneous layer may be left temporary with VAC 
or other wound  dressing according to surgeons’ preference. In contamination classes 1-3, 
the skin is closed   

according to surgeons’ preference.    
 
In case the mesh cannot be safely kept outside the abdominal cavity, patient is intra-
operatively  excluded.    
 
 
 
 
PREEMER TRIAL  27   

 
 
 
In the no mesh group, the rectus aponeurosis is closed in a single aponeurotic layer by using   
slowly absorbable monofilament USP 2-0 or 0 suture by 4:1 small stitch technique. Both the 
length  of the wound and length of the suture material used is measured.   
 
Catalogue of the operative technique will be sent to all participating surgeons to 
standardize the  procedure.   
 
 
14.3 Postoperative treatment   
Postoperative treatment will be accomplished according to standard protocol of each 
participating  hospital.   
 
 
14.4. Mesh (ProgripTM, Medtronic)   
 
A standard 8 cm self-gripping prophylactic mesh will be used in mesh group. The width 
of the  mesh is standard. The length of the mesh is measured and reached over both 
ends of the   
laparotomy opening.   
 
 
 
15.General Reporting Requirements    
Complications (Adverse events) reporting are an investigator’s responsibility to assess and 
report.  Adverse Events (AE) will be identified and captured on the electronic Complications 
eCRF   
throughout the duration of the study as they occur and will be followed until they are 
adequately  resolved or explained.  Any Serious Mesh-Related Adverse Events with 
Clavien-Dindo Classification  3b or more should be reported to primary investigation site 
without delay after the site first learns  of the event.    
 
16. Investigator’s Responsibilities and Qualifications   
 
16.1 General Responsibilities    
The role of the investigator is to implement and manage the day-to-day conduct of the 
clinical  investigation and to ensure data integrity and the rights, safety and well-being 
of the subjects   
 
 

 
PREEMER TRIAL  28   

 
 
involved in the clinical investigation. The participating institution shall appoint an 
appropriately  qualified person to be the site principal investigator.   
Prior to subject enrolment the investigational center must have Institutional review 
board  approval for the study.    
 
Investigators shall be qualified by education, training and experience to assume 
responsibility for  the proper conduct of the clinical investigation. Investigators shall 
disclose potential conflicts of  interest,  including  financial,  that  interfere  with  the  
conduct  of  the  clinical  investigation  or  interpretation of the results. Investigators shall 
be knowledgeable with the method of obtaining  informed consent.    
The Investigator shall ensure compliance with the applicable regulatory requirements and 
ethical   
principles for the process of obtaining informed consent. All protocol deviations should be   
recorded on the Protocol deviation form.    
 
17 Data handling and record keeping   
 
17.1 Confidentiality   
Patient confidentiality will be strictly maintained. Patients will be assigned a Study ID. 
Access to  patient records will be limited to the study group and the Investigator-
delegated study   
coordinator.   
 
 
17.2 Data Management   
Dedicated software and electronic database and the case report forms (eCRF) will be used 
to host  the Clinical Trial data for this study. The database is developed and utilized in 
accordance with   
international requirements and standards applicable to clinical investigations i.e. Good 
Clinical   
Practice (GCP) and is a GCP compliant environment meeting applicable 21 CFR Part 11   
requirements.    
 
18. Case Report Forms   
The electronical Case Report Forms (eCRF) and software are the primary data 
collection  instruments for the study.    

 
 
PREEMER TRIAL  29   

 
 
 
All data requested on the eCRFs will be recorded. All missing data will be explained.   
 
19. Sample Size and Statistical Analysis   
 
19.1 Sample size   
 
To calculate a sample size needed to compare these two groups we estimated a 10 % rate 
of IH in  mesh group and 25 % IH in control group on clinical assessment and ultrasound 
examination.   
Assuming α = 0.05 and power = 80%, we would need 97 patients per group. Further, 
assuming a 2- year dropout rate of 20%, 122 patients per group are needed (totally 244 
patients). The sample   
size is calculated only for the primary outcome, the secondary outcomes will be interpreted 
as   
hypothesis generating only. If the estimated 20% dropout rate exceeds, the sample size 
may be   
recalculated.   
 
All analyses will be performed by or under the guidance of professional statistician and 
following  the CONSORT guidelines.   
 
 
19.2 Allocation   
Patients having emergency midline laparotomy for any indication and fulfilling the inclusion 
criteria  will be randomized prior to surgery after informed consent is signed. Patients are 
randomly   
allocated (1:1 ratio) either to an intervention group or a control group according to a 
computer-  
generated list compiled by a biostatistician otherwise uninvolved in the clinical care of trial   
patients. Allocation will be stratified according to BMI (<30 and ≥30kg/m2), history of 
previous   
laparotomy and age (<65 and ≥65- years) and blocked within strata using random permuted 
blocks  (block size 2, 4, 6 and 8). A separate randomization list will be created for each 
participating   
center. All patients who have an emergency midline laparotomy during randomization 
period are  assessed for eligibility.    

 
 
19.3 Endpoint analysis   
All analyses will be performed primarily according to modified intention to treat (ITT) 
principle.   
Patients who fulfill exclusion criteria intraoperatively (after randomization) will not be 
included in  the analyses. Per protocol analyses will be used as safeguard against the risk 
of falsely claiming   
 
 
PREEMER TRIAL  30   

 
 
equality/superiority. The primary endpoint will be the incidence difference of IHs with 95%   
confidence interval between the study groups during 2-years follow up. Secondary 
outcomes are   
listed previously. The primary endpoint as well as other categorical data will be analyzed by 
the χ2- test or Fisher’s exact test. Student’s t-test or Welch test will be used for continuous 
variable, the   
latter if assumption of homogenous variances does not hold. The incidence of hernia will 
also be   
analyzed using Kaplan-Meier analysis.   
 The linear mixed model (LMM) or generalized linear mixed model (GLMM) will be used for   
repeatedly measured data, the previous for continuous data and latter for categorical data.   
Multiple imputations of missing outcome data will be used for sensitivity analyses. 
Prospectively   
planned subgroup analyses are as follows: BMI>30, previous hernia and contamination 
class 4.   
However, sample size calculation is done only for the primary end point and subgroup 
analyses are  hypothesis generating only. The statistical programs SPSS (IBM Corp. 
Released 2016. IBM SPSS   
Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp) and SAS (version 9.4, SAS 
Institute   
Inc., Cary, NC, USA) will be used for the analyses.   
 
 
 
20. Publication Policy   
 
The trial will be registered with an authorized registry, according to the International   
Committee of Medical Journal Editors (ICMJE) Guidelines, prior to the start of recruitment.    
The success of the trial depends upon the collaboration of all participants. For this reason, 
credit   
for the main results will be given to all those who have collaborated in the trial, through   
authorship and contributor-ship. Authorship decisions will be guided by standard 
requirements for  authorship relating to submission of manuscripts to medical journals. 
These state that authorship  credit should be based only on the following conditions being 
met (http://www.icmje.org):   
• Substantial contribution to conception and design, or acquisition of data, or   

analysis and interpretation of data   
• Substantial contribution to drafting the article or revising it critically for important   
intellectual content   
• Substantial contribution to final approval of the version to be published.   
 
In light of this, the Principal Investigator and the main study group from Oulu and Helsinki   
University Hospitals and Dr Filip Muysoms will be named as authors in any publication, 
subject to   
 
PREEMER TRIAL  31   

 
 
journal authorship restrictions. In addition, all collaborators (surgeons as well as 
biostatistician)   
will be listed as contributors for the main trial publication, giving details of roles in planning,   
conducting and reporting the trial. It is planned that the recruiting surgeons will also be 
named as  authors, if the set target of the number of randomized patients is achieved.   
To maintain the scientific integrity of the trial, data will not be released prior to the first   
publication of the analysis of the primary endpoint, either for trial publication or oral 
presentation  purposes, without the permission of the whole study group. In addition, 
individual collaborators   
must not publish data concerning their patients, which is directly relevant to the questions 
posed  in the trial until the first publication of the analysis of the primary endpoint.    
 
 
20.1. Publication Plan   
The protocol of the trial will be published at the beginning of the trial. The results 
concerning the  primary end point and results of secondary endpoints within 2 years follow 
up will be published  once included patients have reached 2 years follow-up. The results 
of 5 years follow up will be   
published.   
 
 
 
21. References   
 
(1) Höer J, Lawong G, Klinge U, Schumpelick V. Einflussfaktoren der 
Narbenhernienentstehung   
Retrospektive Untersuchung an 2.983 laparotomierten Patienten über einen Zeitraum von 
10   
Jahren. Der Chirurg 2002;73:474-80.   
(2) Mudge M, Hughes LE. Incisional hernia: A 10 year prospective study of incidence and 
attitudes.  Br J Surg 1985;72:70-71.   
(3) Sajid MS, Bokhari SA, Mallick AS, Cheek E, Baig MK. Laparoscopic versus open repair 
of   
incisional/ventral hernia: a meta-analysis. The American Journal of Surgery 2009;197:64-
72.   
(4) Harlaar JJ, Deerenberg EB, Dwarkasing RS, Kamperman AM, Kleinrensink GJ, Jeekel 
J, et al.   
Development of incisional herniation after midline laparotomy. BJS Open 2017;1:18-23.   
(5) Patel SV, Paskar DD, Nelson RL, Vedula SS, Steele SR. Closure methods for 
laparotomy incisions  for preventing incisional hernias and other wound complications. The 
Cochrane Database of   

Systematic Reviews 2017;11.   
(6) Fink C, Baumann P, Wente MN, Knebel P, Bruckner T, Ulrich A, et al. Incisional hernia 
rate 3   
years after midline laparotomy. Br J Surg 2014;101:51-4.   
(7) Kroese LF, Gillion J, Jeekel J, Kleinrensink G, Lange JF. Primary and incisional ventral 
hernias are  different in terms of patient characteristics and postoperative complications - A 
prospective   
cohort study of 4,565 patients. International Journal of Surgery 2018;51:114-9.   
 
 
PREEMER TRIAL  32   

 
 
 
(8) Bjork D, Cengiz Y, Weisby L, Israelsson LA. Detecting Incisional Hernia at Clinical and   
Radiological Examination. Surg Technol Int 2015;26:128-31.   
(9) Fischer JP, Basta MN, Mirzabeigi MN, Bauder AR, Fox JP, Drebin JA, et al. A Risk 
Model and Cost  Analysis of Incisional Hernia After Elective, Abdominal Surgery Based 
Upon 12,373 Cases: The Case  for Targeted Prophylactic Intervention. Annals of Surgery 
2016;263:1010-1017.   
(10) Bickenbach KA, M.D, Karanicolas, Paul J., M.D., Ph.D, Ammori JB, M.D, Jayaraman, Shiva,   
M.D., M.E.S.C, Winter JM, M.D, Fields RC, M.D, et al. Up and down or side to side? A 
systematic   
review and meta-analysis examining the impact of incision on outcomes after abdominal 
surgery.  Am J of Surgery 2013;206:400-9.   
(11) Brown SR, Goodfellow PB. Transverse verses midline incisions for abdominal surgery.   
Cochrane Database Syst Rev 2005;4. doi(4):CD005199.   
(12) Millbourn D, Wimo A, Israelsson L. Cost analysis of the use of small stitches when 
closing   
midline abdominal incisions. Hernia 2014;18:775-80.   
(13) 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. The Lancet 2015;386:1254-1260.   
(14) Muysoms F, Antoniou S, Bury K, Campanelli G, Conze J, Cuccurullo D, et al. 
European Hernia   
Society guidelines on the closure of abdominal wall incisions. Hernia 2015;19:1-24.   
(15) Thankam FG, Palanikumar G, Fitzgibbons RJ, Agrawal DK. Molecular Mechanisms and   
Potential Therapeutic Targets in Incisional Hernia. J Surg Res 2019;236:134-43.   
(16) Xing L, Culbertson EJ, Wen Y, Franz MG. Early laparotomy wound failure as the 
mechanism for  incisional hernia formation. J Surg Res 2013;1;182:35.   
(17) Chang N, Goodson WH,3rd, Gottrup F, Hunt TK. Direct measurement of wound and 
tissue   
oxygen tension in postoperative patients. Ann Surg 1983;197:470-478.   
(18) Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis-effect of 
oxygen   
gradients and inspired oxygen concentration. Surgery 1981;90:262-270.   
(19) Aicher BO, Woodall J, Tolaymat B, Calvert C, Monahan TS, Toursavadkohi S. Does 
perfusion   
matter? Preoperative prediction of incisional hernia development. Hernia 2019;2. doi:   
10.1007/s10029-019-02018-3.    
(20) Harrison B, Sanniec K, Janis JE. Collagenopathies-Implications for Abdominal Wall   
Reconstruction: A Systematic Review. Plast Reconstr Surg Glob Open 201624;4:e1036.   
(21) Bosanquet DC, Ansell J, Abdelrahman T, Cornish J, Harries R, Stimpson A, et al. 
Systematic   
Review and Meta-Regression of Factors Affecting Midline Incisional Hernia Rates: Analysis 
of 14   
618 Patients. PLoS ONE 2015;10(9).   
(22) Basta MN, Kozak GM, Broach RB, Messa CA,4th, Rhemtulla I, DeMatteo RP, et al. 
Can We   
Predict Incisional Hernia?: Development of a Surgery-specific Decision-Support Interface. 
Ann Surg  2019;270:544-553.   

(23) Ah-Kee EY, Kallachil T, O'Dwyer PJ. Patient awareness and symptoms from an incisional   
hernia. Int Surg 2014;99:241-6.   
(24) Cassar K, Munro A. Surgical treatment of incisional hernia. Br J Surg 2000;89:534-45.   
(25) Emby DJ, Aoun G. CT technique for suspected anterior abdominal wall hernia. AJR 
Am J   
Roentgenol 2003;181:431-3.   
 
PREEMER TRIAL  33   

 
 
 
(26) Bloemen A, van Dooren P, Huizinga BF, Hoofwijk AG. Comparison of ultrasonography 
and   
physical examination in the diagnosis of incisional hernia in a prospective study. Hernia   
2012;16:53-57.   
(27) Hojer AM, Rygaard H, Jess P. CT in the diagnosis of abdominal wall hernias: a 
preliminary   
study. Eur Radiol 1997;7:1416-8.   
(28) den Hartog D, Dur AH, Kamphuis AG, Tuinebreijer WE, Kreis RW. Comparison of   
ultrasonography with computed tomography in the diagnosis of incisional hernias. Hernia   
2009;13:45-8.   
(29) Aguirre DA, Casola G, Sirlin C. Abdominal wall hernias: MDCT findings. AJR Am J 
Roentgenol   
2004;183:681-90.   
(30) Lassandro F, Iasiello F, Pizza NL, Valente T, Stefano ML, Grassi R, et al. Abdominal 
hernias:   
Radiological features. World J Gastrointest Endosc 2011;16:110-17.   
(31) Bittner R, Bingener-Casey J, Dietz U, Fabian M, Ferzli G, Fortelny R, et al. Guidelines 
for   
laparoscopic treatment of ventral and incisional abdominal wall hernias. International 
Endohernia  Society (IEHS)—Part 1. Surg Endosc 2014;28:2-29.   
(32) Albertsmeier M, Seiler CM, Fischer L, Baumann P, Husing J, Seidlmayer C, et al. 
Evaluation of   
the safety and efficacy of MonoMax(R) suture material for abdominal wall closure after 
primary   
midline laparotomy-a controlled prospective multicentre trial: ISSAAC [NCT005725079.   
Langenbecks Arch Surg 2012;397:363-71.   
(33) Seiler C, Baumann P, Kienle P, Kuthe A, Kuhlgatz J, Engemann R, et al. A 
randomised, multi-  
centre, prospective, double blind pilot-study to evaluate safety and efficacy of the non-
absorbable  Optilene Mesh Elastic versus the partly absorbable Ultrapro Mesh for incisional 
hernia repair. BMC  Surg 2010;10:21-21.   
(34) Dietz UA, Hamelmann W, Winkler MS, Debus ES, Malafaia O, Czeczko NG, et al. An 
alternative  classification of incisional hernias enlisting morphology, body type and risk 
factors in the   
assessment of prognosis and tailoring of surgical technique. J Plast Reconstr Aesthet Surg   
2007;60:383-8.   
(35) Korenkov M, Paul A, Sauerland S, Neugebauer E, Arndt M, Chevrel JP, et al. 
Classification and  surgical treatment of incisional hernia. Results of an experts' meeting. 
Langenbecks Arch Surg   
2001;38:65-73.   
(36) Muysoms FE, Miserez M, Berrevoet F, Campanelli G, Champault GG, Chelala E, et al.   
Classification of primary and incisional abdominal wall hernias. Hernia 2009;13:407-414.   
(37) Diener M, Voss S, Jensen K, Büchler M, Seiler C. Elective Midline Laparotomy 
Closure: The   
INLINE Systematic Review and Meta-Analysis. Annals of Surgery 2010;251:843-856.   
(38) van’t Riet M, Steyerberg EW, Nellensteyn J, ym. Meta-analysis of techniques for 
closure of   
midline abdominal incisions.BJS 2002;89:1350-6.   

(39) Jairam A, Timmermans L, Eker H, ym. Prevention of incisional hernia with prophylactic 
onlay   
and sublay mesh reinforcement versus primary suture only in midline laparotomies 
(PRIMA): 2-  
year follow-up of a multicentre, double-blind, randomised controlled trial. Lancet 
2017;390:567-  
76.   
 
 
 
 
 
PREEMER TRIAL  34   

 
 
 
(40) Borab Z, Shakir S, Lanni, M, et al. Does prophylactic mesh placement in elective, 
midline   
laparotomy reduce the incidence of incisional hernia? A systematic review and meta-
analysis.   
Surgery 2016;161:1149-63.   
(41) Mingoli A1, Puggioni A, Sgarzini G, Luciani G, Corzani F, Ciccarone F, Baldassarre E, 
Modini C.  Incidence of incisional hernia following emergency abdominal surgery. Ital J 
Gastroenterol   
Hepatol. 1999;31:449-53.   
(42) Burns FA, Heywood EG, Challand CP, Lee MJ. Is there a role for prophylactic mesh in   
abdominal wall closure after emergency laparotomy? A systematic review and meta-
analysis.   
Hernia 2019. doi: 10.1007/s10029-019-02060-1   
(43) Kurmann A, Barnetta C, Candinas D, Beldi G. Implantation of Prophylactic 
Nonabsorbable   
Intraperitoneal Mesh in Patients With Peritonitis Is Safe and Feasible. World J Surg 
2013;37:1656- 60.   
(44) Argudo N, Pereira J, Sancho J, et al. Prophylactic synthetic mesh can be safely used 
to close   
emergency laparotomies, even in peritonitis. Surgery 2014;156:1238-44.   
(45) Gillion J, Sanders D, Miserez M, Muysoms F. The economic burden of incisional 
ventral hernia  repair: a multicentric cost analysis. Hernia 2016;20:819-30.   
 
(46) Muysoms F, Mizered M, Berrevoet F, et al. Classification of primary and incisional 
abdominal  wall hernias. Hernia 2009;13:407-14.   
(47) McCarthy M, Jr, Jonasson O, Chang CH, et al. Assessment of patient functional 
status after   
surgery. J Am Coll Surg. 2005;201:171–8.   
 
(48) Jairam AP, Wilson M, Steyerberg EW, Jeekel J, Lange JF. Patient reported 
outcome   
measurements in the diagnosis of incisional hernia: PROMIS questionnaire, a pilot 
study. J Surg  Res. 2016;203:378–82.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
PREEMER TRIAL  35