Mesh versus suture repair for umbilical hernias a prospective by qqk83867

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									      Mesh versus suture repair for umbilical hernias: a double
               blinded, randomised controlled trial

                              Table of Contents



Chapter         Titel                                                       Page

                Amendments                                                     3
                Confidentiality statement                                      4
                Investigators signature of agreement                           5
                Investigators signature of agreement –
                                                                               6
                Primary investigator copy
                Study Committee                                                7
                Study participants                                             8
                Summary                                                        9

1.0             INTRODUCTION                                                  10
        1.1     Anatomy and Pathofysiology                                    12
        1.2     Complications                                                 13
        1.3     Risk Factors for hernia recurrence                            13

2.0             PATIENTS AND METHOD                                           14
        2.1     Statistical analysis                                          14
        2.2     Practical implication of trial                                15
        2.3     Method of repair and per-operative procedure                  16
        2.3.1   Method of mesh repair                                         17
        2.3.2   Method of suture repair                                       18
        2.4     Post-operative procedure                                      18

3.0             FOLLOW-UP                                                     21

                BIBLIOGRAPHY                                                  22
                TABLES                                                        23

                Appendix 1: Patient Information and Informed Consent Form




                                                                               2
  Mesh versus suture repair for umbilical hernias: a double
           blinded, randomised controlled trial

                            Amendments




Please note the following revisions have been made to the protocol.

Page    AMENDMENT                                      Date Inserted




                                                                       3
   Mesh versus suture repair for umbilical hernias: a double
            blinded, randomised controlled trial

                          Confidentiality statement

                    Investigators signature of confidentiality

The information contained within this document is the intellectual property of
the studies writing committee.


This document is provided to you in confidence as an investigator or potential
investigator. Furthermore this document may be provided to consultants, staff,
sponsors and applicable independent ethics committees by (potential)
investigators.


It is to be understood that no part of this document may be disclosed to others
without the explicit written consent of the study coordinator prof. dr. J. Jeekel
except to the extent necessary to obtain informed consent.




Signature:                                 Date:         -       - 200




Name:


Centre:




                                                                                    4
   Mesh versus suture repair for umbilical hernias: a double
            blinded, randomised controlled trial

                          Clinical study protocol

                    Investigators signature of agreement

I, the investigator, agree to conduct the clinical study as described in this
protocol. I will adhere to national and local guidelines and will conduct this
study in accordance with current Good Clinical Practice (GCP) guidelines.

I have examined the study protocol in full and discussed the contents and
objectives of this protocol with the primary investigator.

No modifications to the protocol shall be made without prior agreement of
both the primary investigator and myself. All modifications must be
documented in writing in the amendment section on page 2. I agree to
cooperate fully with monitoring and audits by the study committee and health
authorities in allowing full access to all relevant source data and documents.

                               Personal copy

INVESTIGATOR


Signature:                              Date:         -     - 200


Name:


Centre:




PRIMARY INVESTIGATOR


Signature:                              Date:         -     - 200


Name:




                                                                            5
                             Mesh versus suture repair for umbilical hernias: a double
                                      blinded, randomised controlled trial

                                                    Clinical study protocol

                                              Investigators signature of agreement




                                                                                                            Please remove this copy
Please remove this copy


                          I, the investigator, agree to conduct the clinical study as described in this
                          protocol. I will adhere to national and local guidelines and will conduct this
                          study in accordance with current Good Clinical Practice (GCP) guidelines.

                          I have examined the study protocol in full and discussed the contents and
                          objectives of this protocol with the primary investigator.

                          No modifications to the protocol shall be made without prior agreement of
                          both the primary investigator and myself. All modifications must be
                          documented in writing. I agree to cooperate fully with monitoring and audits by
                          the study committee and health authorities in allowing full access to all
                          relevant source data and documents.

                                                   Primary investigator copy

                          INVESTIGATOR


                          Signature:                               Date:        -      - 200


                          Name:


                          Centre:




                          PRIMARY INVESTIGATOR


                          Signature:                               Date:        -      - 200


                          Name:

                          Please remove this copy and return to:
                          Erasmus MC, Department of Surgery, H.H. Eker,
                          ‘s Gravendijkwal 230, 3015 CE, Rotterdam


                                                                                                       6
   Mesh versus suture repair for umbilical hernias: a double
            blinded, randomised controlled trial

                            Study Committee


Study coordinator:
H.H. Eker, MD
Department of Surgery,
Erasmus MC, Rotterdam


Principal Investigators:
J. Jeekel, MD, PhD.
Professor of Surgery
Department of Surgery
Erasmus MC, Rotterdam


Writing committee:

H.H. Eker, MD
Department of Surgery
Erasmus MC, Rotterdam

J.F. Lange, MD, PhD.
Professor of Surgery
Department of Surgery,
Erasmus MC, Rotterdam

J. Jeekel, MD, PhD.
Professor of Surgery
Department of Surgery
Erasmus MC, Rotterdam

W.C.J. Hop, PhD.
Statistician
Department of Epidemiology & Biostatistics
Erasmus MC, Rotterdam




                                                               7
   Mesh versus suture repair for umbilical hernias: a double
            blinded, randomised controlled trial

                              Study participants
Rules regarding publication
Participating investigators that include 10% or more of the required patients
will be asked to co-author publications regarding the study. Vancouver
guidelines will be adhered to.

 Erasmus Medisch Centrum Rotterdam       Ikazia Ziekenhuis
 dr. Molewaterplein 40/50                Montessoriweg 1
 3015 GD Rotterdam                       3083 AN Rotterdam
 Telephone: 010-4639222                  Telephone: 010-2975000
 Fax: 010-4635307                        Fax: 010-4865900
                                         W.F. Weidema, MD, PhD.

 MCRZ Medisch Centrum Rijnmond Zuid      Reinier de Graaf Groep, lokatie Reinier de
 Olympiaweg 350                          Graaf Gasthuis
 3078 HT Rotterdam                       Postbus 5011
 Telephone: 010-2911911                  2600 GA Delft
 Fax: 010-4323481                        Telephone: 015-2604025
                                         Fax: 015-2603599
 Groene Hilledijk 315                    H. Oei, MD, PhD.
 3075 EA Rotterdam                       (L.P.S. Stassen, MD, PhD.)
 Telephone: 010-2903000
 Fax: 010-2903805
 E. vd Harst, MD, PhD.

 Sint Franciscus Gasthuis                IJsselland Ziekenhuis
 Kleiweg 500                             Postbus 690
 3045 PM Rotterdam                       2900 AR Capelle aan de IJssel
 Telephone: 010-4616161                  Telephone: 010-2585000
 Fax: 010-418644                         I. Dawson, MD, PhD.
 C.H.A. Wittens, MD, PhD.

 Onze Lieve Vrouwe Gasthuis              Isala Kliniek
 Postbus 95500                           Postbus 10500
 1090 HM Amsterdam                       8000 GM Zwolle
 Telephone: 020-5999111                  Telephone: 038 - 424 20 00
 Fax: 020-5993840                        D. van Geldere, MD, PhD.
 M.P. Simons, MD, PhD.




                                                                                8
   Mesh versus suture repair for umbilical hernias: a double
            blinded, randomised controlled trial

                                   Summary

Purpose
The purpose of the present study is to investigate whether or not the use of
mesh is indicated in the repair of all size umbilical hernias as to reduce the
rate of recurrence. This method is regularly used in umbilical hernia
reconstruction although most surgeons repair small hernias using suture
repair (fascia adaptation). Especially risk factors for hernia recurrence such as
hernia size and BMI > 30 kg/m2 need to be evaluated and correlated to the
method of hernia repair.

Study design
Randomised controlled, double blinded, multi-centre trial.
300 consecutive patients with an umbilical hernia will be included in the study.
Patients will be randomised in one of two groups of 150 patients each. Group
1 will include patients that will undergo primary (suture) repair; group 2
umbilical hernias will be repaired using a pre-peritoneal, flat polypropylene
mesh in a tension free fashion.
Stratification will be utilized for the size of the hernia (<2 cm or ≥2 cm) and the
participating centre. Patients will visit the outpatient clinic after 2-3 weeks and
after 3, 12 and 24 months.

The cumulative hernia recurrence rate during the 2-years follow-up period will
be the primary outcome of the study. Complications, pain and QOL are
secondary endpoints.

Statistical analysis
All analyses will be performed according to the intention to treat principle and
as specified in the protocol.

Financial support
None.




                                                                                 9
      Mesh versus suture repair for umbilical hernias: a double
               blinded, randomised controlled trial

                                     Protocol

1.0
INTRODUCTION
In 2003, 4518 umbilical hernias were repaired in the Netherlands
(www.prismant.nl). Recurrence of umbilical hernia is a common problem in
the adult population. Recently recurrence rates of 1% have been reported
through the use of mesh prosthetics in all size umbilical hernias and pre-
peritoneal mesh is thought to become the standard in inguinal, incisional and
umbilical hernia repair (see table 1) [1, 2].
The Mayo technique and its modifications could not stand the test of time: a
recurrence rate of 20% and higher is not acceptable for any surgical
procedure [3]. Evidence from one retrospective study suggests that the repair
of umbilical hernias larger than 3 cm should be performed using prosthetic
mesh in order to avoid the high recurrence rates of primary repair of larger
hernias. The same study reported an overall recurrence rate of 13% after a
mean follow up of 30 months [4].
Our previous experience in Rotterdam (as of yet unpublished data, IKAZIA
hospital) has yielded results similar to those published. In a retrospective
analysis, 110 patients were seen in the outpatient clinic. Suture repair was
shown to have a recurrence rate of 14% (n=98) after a mean follow up of 32
months. No recurrences were seen in patients with mesh repair (n=12).
The favourable results of primary herniorraphy (in the study of Schumacher et
al) in umbilical hernias smaller than 2 cm (measured by ultrasound) [4] led us
to the question whether or not primary repair is still acceptable practice for
small hernias (table 2). Luijendijk et al have previously described the
beneficial effect of mesh repair in incisional hernias [5].
Nyhus critically comments that the use of prosthetic materials, regardless of
hernia type or size has reached worrying levels. He and others propose
individually tailored hernia repair [6, 7]. One might furthermore argue that the




                                                                             10
use of mesh in small hernias is time consuming, in general more difficult and
that the placement of mesh in a small (less than 2 cm’s) hernia will lead to
enlargement of the fascial defect. In the previous randomised controlled trial
Arroyo and co-workers have used surgeon-fabricated mesh-plugs to close
fascial defects smaller than 3 cm’s staying in the pre-peritoneal plane [1]. A
similar technique has been employed by Kurzer et al to seal umbilical defects
smaller than 3 cm’s. A mesh cone was inserted and fixed using non-
absorbable sutures (2/0 polypropylene) in the four quadrants [8].


As of yet, as indicated in table 1, only one randomised trial has been
conducted to compare the recurrence rates of suture and mesh repair used in
umbilical hernia reconstruction.


Usher and Wallace introduced the use of polypropylene mesh in hernia repair
in 1958 [9]. It is still widely used in abdominal hernia repair, mainly for its mild
reactivity in human tissues and the ability to not aggravate abdominal
infections [10, 11]. According to the criteria first proposed by Scales [12] and
Cumberland [13] polypropylene mesh has near ideal properties; it is pliable,
flexible and holds sutures well. More recently criteria were redefined by
Debodinance et al. [14] as: “An ideal implant material must: not undergo
physical modification by tissue fluids, be chemically inert, not trigger
inflammatory    or   foreign   body    cell   response    in   body   tissues,   be
noncarcinogenic and nonallergenic, be capable of resisting mechanical stress
and sterilization, and be able to be manufactured in the necessary shape.
Polyester, polypropylene and expansive polytetrafluoroethylene fulfil these
criteria”.


1.1
Anatomy and Pathofysiology
Important in the embryology of the umbilical defect is the fusion of ectoderm
and embryonic mesoderm to form the fascial margin of the umbilical ring. To
allow the passage of the umbilical arteries and the umbilical vein to the
umbilical cord, an abdominal wall defect is present from the third week of


                                                                                 11
gestation onwards. After birth, thrombosis of both the arteries and the vein
occurs and thus facilitates contraction of the umbilical ring by cicatrisation.
Subsequently the weakest area of the umbilical ring is the superior aspect of
it, the area between the umbilical vein and the cranial margin of the umbilical
ring. The relative lack of elastic fibres in the obliterated umbilical vein is held
responsible for this weakness. This is the typical site for herniation in the
paediatric population when cicatrisation is impaired or the newly formed scar
is subjected to elevated intra abdominal pressures.


The anatomical margins of the so-called umbilical canal (in adults) are the
umbilical fascia from posterior, the linea alba from anterior and the medial
edges of the rectus sheaths.
The adult umbilical hernia does not seem to result from the persisting juvenile
hernia (Only 10% of adults with an umbilical hernia have a history of
childhood herniation [15]). The adult hernia is an acquired hernia and
represents herniation through the umbilical canal probably under influence of
increased intra-abdominal pressure. Predisposing factors are obesity, multiple
pregnancies, ascites and large intra-abdominal tumours.


1.2
Complications
Hernia incarceration is regularly seen in cirrhotic patients with ascites. Hernia
repair is associated with high morbidity, mortality and recurrence if attempted
without prior management of ascites [16-18].


1.3
Risk Factors for hernia recurrence
As previously described hernia size as measured by ultrasound [4] seems to
be a risk factor for recurrence. Obesity (defined as a BMI over or equal to 30
kg/m2) has been shown to increase the risk of incisional hernia recurrence
[19, 20]. A meta-analysis by Sauerland et al. showed that the relative risks
(RR) of recurrence in 7 studies looking into the association of obesity and
recurrence were homogeneous (p=0.15) [20]. Until recently obesity was still


                                                                                12
regarded an indirect risk factor leading to recurrence through a higher rate of
wound infection.
It remains unclear whether obesity leads to hernia recurrence through
increased abdominal pressure, difficulty in surgery or if it is an indicator for an
inherent structural and healing defect.
Further risk factors for incisional hernia were identified by many authors and
divided into major and minor by Yahchouchy and colleagues (see table 3)
[21].


          Major factors                        Minor factors
          Chronic lung disease                 Age
          Obesity                              Male gender
          Steroids                             Post-operative ventilation
          Type II diabetes mellitus            Renal failure
          Malnutrition                         Connective tissue disorders
          Jaundice                             Malignancy
          Radiotherapy                         Transfusion
          Chemotherapy                         Anaemia
          Oral anticoagulants

Table 3: Patient-related risk factors for incisional hernia


As of yet there is insufficient evidence to suggest that, except for obesity and
hernia size, the risk factors mentioned above are also of influence in the
development of the umbilical hernias [4].
In the light of this trial it is therefore useful to at least consider all major risk
factors common to the population and the demographic minor risk factors in
the analysis (underlined in table 3). Umbilical hernias with a diameter of 4 cm
or larger will be excluded from participation for ethical reasons (very high
recurrence rate after suture repair, see table 2).


2.0
PATIENTS AND METHODS
Inclusion criteria are defined as follows:
      •   Umbilical hernia diagnosed
      •   Age ≥ 18 years
      •   Primary umbilical hernia



                                                                                  13
       •   Signed Informed consent


Exclusion criteria:
       •   Umbilical hernia ≥ 4 cm diameter
       •   Recurrence
       •   Midline laparotomy
       •   Ascites/Cirrhosis
       •   ASAi score IV or above
       •   Incarcerated hernia/emergency procedures


“Intention to treat”
Patients randomised for mesh hernia repair that for any of reason receive
suture repair (or vice versa) will remain in the group randomised for.


In this study the hernia recurrence rate during a 24 months follow-up period is
the primary study endpoint. Post-operative morbidity and complications are
secondary study outcomes . The influence of hernia size will be studied.




2.1
Practical implication of trial
All patients eligible to take part in this trial will be informed in depth. The
patients will be offered the patient information letter (“Patiënt Informatie
Folder”/ PIF) and will be asked to sign the informed consent form (CRF-1.1ii).


Patients diagnosed with an umbilical hernia but not eligible to take part in the
trial (not willing, exclusion/ inclusion criteria not met) need to be accounted for
on the basis of the CONSORT recommendations for improving the quality of
reports of parallel-group randomized trials [22]. A separate form is made
available for this purpose.
Preceding the procedure, risk factors as described on CRF-2 (pre-operative
workup) will be assessed by a physician. Further assessment will consist of

i
     American Society of Anaesthesiologists
ii
     Case Record Form

                                                                                14
physical examination and a quality of life evaluation (MOS SF-36 health
surveyi and EQ-5D).
Demographics and clinically relevant patient history and relevant other
diagnoses, medication, ASA score are also included in the pre-operative
evaluation.
The patients will be placed into one of the two study groups through the use of
computer-generated numbers. Randomisation will take place after the size of
the hernia has been established during surgery using either Hegar dilators or
a sterile ruler. Therefore two sets of sealed envelopes will be present at the
operating theatre. The patient will be kept unaware of the randomisation (for
blinding purposes). The investigator in charge will also remain blinded to the
method of hernia repair.
Ware and Sherbourne have conceptualised the previously mentioned MOS
SF-36 health survey for English- speaking patients in 1992. It assesses the
general health in patients older than 14 years with an unlimited variety of
disease [23]. In 1998 the translations of MOS SF-36 was validated for the
Dutch language [24]. The EuroQoL-5D (EQ-5D) [25] has been validated for
the Dutch language as well as for numerous other languages as an efficient
non disease specific quality of life measure.


2.2
Method of repair and per- operative procedure
All repairs will take place using a method for which consensus was reached
by all participating centres. This includes a paraumbilical incision, dissection
(avoiding resection) of the hernia sac (figure 1) and restoration of the sac and
its contents into the abdominal cavity in both groups. Per-operative resection
of the sac must be recorded on the patient’s operation report (part of CRF-3).
Closure of the subcutaneous tissue and skin may be achieved using a method
chosen by the individual surgeon.




i
    Medical Outcomes Study Short Form

                                                                             15
Figure 1: pre-reconstruction transverse section of umbilical hernia


There are no limitations concerning the method of anaesthesia used in either
form of repair. The use of local, general or spinal anaesthesia is permitted in
this trial.
The use of intravenous antibiotics as prophylaxis is acceptable but not
mandatory. Furthermore, routine administration of thrombosis prophylaxis
should be considered in the form of bodyweight adjusted LMWH.
Case record form 3 (per-operative procedure) asks for completion of all fields
noted, such as technical details of procedure (incision, size of the defect and
the use of drains), duration of procedure, complications during procedure
(including       conversion      to   other      procedure),   thrombosis   prophylaxis,
intravenous antibiotics and method of anaesthesia.




2.2.1
Method of mesh repair
Mesh repair should take place using a flat polypropylene mesh (BardMesh/
Prolene)* placed in the pre-peritoneal plane. Fixation of the mesh should be
achieved using 0/0 individual, non-absorbable sutures (monofilament
Prolene). For evaluation purposes it is necessary to note the batch number of
the mesh used. The overlap achieved in repair should be at least 3 cm’s [26]
in each direction of the circular mesh (see figure 2).


*
    BardMesh is a trademark of C.R. Bard, Inc.
    Prolene is a trademark of Ethicon, Inc.

                                                                                     16
Figure 2: Exploded view and transverse section of mesh placement in
umbilical hernia repair

In mesh hernia repair the umbilical defect should not be enlarged during the
repair procedure. If the surgeon sees need to enlarge the umbilical defect
during the operation (which is not the preferred procedure) the enlargement of
the defect must be noted in the operation report. The surgeon is permitted to
close the fascia defect (after mesh insertion) using sutures if this is possible in
a “tension free fashion” to protect the mesh from contact with umbilical skin. In
order to protect the viscera it is possible to place omentum or the remains of
the hernia sac between viscera and mesh. The use of drains is permitted.
Closure of the subcutaneous tissue and skin may be achieved using a method
chosen by the individual surgeon.




2.2.2
Method of suture repair
Suture repair of the umbilical defect will consist of adaptation of the fascia
(linea   alba)   by   interrupted/continuous,   non-absorbable      polypropylene
(monofilament Prolene) sutures of thickness 0/0 (figure 3) in transverse
direction. The suture length to wound length ratio should be 4:1. In this study
it is not permissible to perform Mayo (vest-over-pants) reconstruction of the


                                                                                17
umbilical defect.




Figure 3: Transverse section of fascia adaptation in suture repair

2.3
Post-operative procedure
Post-operative analgesics may consist of diclofenac three times daily 50 mg
and paracetamol three times daily 1000 mg (or equivalent) administered orally
for six days after surgery. A visual analogue scale (VAS) will be employed to
evaluate post-operative pain.
Time points will be pre-operative, directly post-operative, at home day 1 until 6
and after 3, 12 and 24 months.
Surgical wounds are examined for signs of haematoma and seroma before
the patient is allowed to return home.


Definitions:
      •   Haematoma: accumulation of blood in the wound area, which warrants
          surgical exploration and intervention.
      •   Seroma: accumulation of clear fluid in the surgical field as diagnosed
          by aspiration of clear fluid.
      •   Criteria for defining a Surgical Site Infection (SSI) [27]:


Superficial Incisional SSI
Infection occurs within 30 days after the operation


                                                                                   18
and
infection involves only skin or subcutaneous tissue of the incision
and at least one of the following:
       1. Purulent drainage, with or without laboratory confirmation, from the
          superficial incision.
       2. Organisms isolated from an aseptically obtained culture of fluid or
          tissue from the superficial incision.
       3. At least one of the following signs or symptoms of infection: pain or
          tenderness, localized swelling, redness or heat and superficial
          incision is deliberately opened by surgeon, unless incision is
          culture-negative.
       4. Diagnosis of superficial incisional SSI by the surgeon or attending
          physician.




Do not report the following conditions as SSI:
   1. Stitch abscess (minimal inflammation and discharge confined to the
       points of suture penetration).
   2. Incisional SSI that extends into the fascial and muscle layers (see deep
       incisional SSI).


Deep Incisional SSI
Infection occurs within 30 days after the operation if no implant is left in place
or within 1 year if implant is in place and the infection appears to be related to
the operation and
infection involves deep soft tissue (e.g., fascial and muscle tissue) of the
incision and at least one of the following:
   1. Purulent drainage from the deep incision but not from the organ / space
       component of the surgical site.
   2. A deep incision spontaneously dehisces or is deliberately opened by a
       surgeon when the patient has at least one of the following signs or


                                                                                19
         symptoms: fever (>38°C), localized pain, or tenderness, unless site is
         culture negative.
      3. An abscess or other evidence of infection involving the deep incision is
         found on direct examination, during reoperation, or by histopathologic
         or radiologic examination.
      4. Diagnosis of a deep incisional SSI by a surgeon or attending physician.
      Notes:
         1. Report infection that involves both superficial and deep incision
            sites as deep incisional SSI.
         2. Report an organ/space SSI that drains through the incision as a
            deep incisional SSI.


Organ/Space SSI
Infection occurs within 30 days after the operation if no implant is left in place
or within 1 year if implant is in place and the infection appears to be related to
the operation
and
infection involves any part of the anatomy (e.g., organs or spaces), other than
the incision, which was opened or manipulated during an operation and at
least one of the following:
      1. Purulent drainage from drain that is placed through a stab wound into
         the organ / space.
      2. Organisms isolated from an aseptically obtained culture of fluid or
         tissue in the organ space.
      3. An abscess or other evidence of infection involving the organ / space
         that is found on direct examination, during reoperation, or by
         histopathologic or radiologic examination.
      4. Diagnosis of a deep organ / space SSI by a surgeon or attending
         physician.


3.0
FOLLOW-UP
Re-herniation rate will be assessed after 2-3 weeks (routine follow-up). In


                                                                                 20
addition 3, 12 and 24 months post-operative follow-up are performed (CRF-5
at 2 weeks, 3, 12, and 24 months). The blinded observer will examine the
blinded patient for any signs of recurrent umbilical hernia. The patient will
undergo ultrasound imaging at the 24-month follow-up point. An independent
radiologist will perform the ultrasound imaging and note possible re-herniation
on a sketch.
The patient is asked to complete a MOS SF-36 and EQ-5D questionnaire (as
part of the quality of life evaluation) at the 12-month follow-up point (see table
5).


3.1
Statistical considerations
Randomization of patients will be done in the operation theatre using sealed
envelopes in centres outside the Netherlands, and by telephone for Dutch
centres, after intra-operative measurement of the defect size.
Stratification wil be done by centre and defect size (<=2 vs > 2 cm).


Primary endpoint.
The primary endpoint in this study is the recurrence rate during a follow-up
period of 24 months. Kaplan-Meier curves will be constructed to determine the
cumulative recurrence rate of the umbilical hernia in the two study arms
Comparison will be done using the stratified Logrank test with stratification by
the defect size. P<0.05 (two-sided) will be the limit of significance. Whether
there is effect modification, i.e. whether the difference in recurrence rate
between both study arms depends on the defect size, will be investigate by
Cox-regression.
300 Patients will be randomised in this study ( 2 groups of 150 each). Group
sizes are based on Fisher’s exact test with two-sided alpha=0.05 and a power
of 80% and are based on an expected lowering of the recurrence rate from 13
to 3% through the use of mesh at 24 months follow-up. Assuming a difference
of 10% (13% vs 3%) in recurrence rates at 24 months, 135 patients in each
group are required at two-sided alpha of 0.05 and a power of 80% (Fisher’s
exact test). The power of the study with these numbers will be greater than


                                                                               21
80% using the intended logrank test in case the hazard rates for recurrence
are proportional. To allow for some dropouts, the sample size is set at
150/group.


Secundary endpoints
   •   VAS pain score: the longitudinal measurements of Vas scores will be
       compared between both groups with repeated measurements Anova
       using SAS PROC MIXED software.
   •   The two QOL scales (SF-36 and EQ-5D) at 12 months will be
       compared using Analysis of covariance while allowing for baseline
       score, age and gender.
   •   Complication rates will be compared using Fisher’s exact test.


All data will be analyzed on an intention to treat basis. A per-protocol analysis
excluding severe violations of the protocol will also be performed.


Pain VAS scores and QOL will be compared using the Mann-Whitney test.
300 consecutive patients with an umbilical hernia will be included in the study.
Patients will be randomised in one of two groups of 150 patients each. The
use of blocked randomisation is prudent to maintain good balance between
groups. Data will be analyzed on an intention to treat basis.




                                                                              22
BIBLIOGRAPHY
1.   Arroyo, A., et al., Randomized clinical trial comparing suture and mesh
     repair of umbilical hernia in adults. Br J Surg, 2001. 88(10): p. 1321-3.
2.   Arroyo Sebastian, A., et al., Is prosthetic umbilical hernia repair bound
     to replace primary herniorrhaphy in the adult patient? Hernia, 2002.
     6(4): p. 175-7.
3.   Celdran, A., et al., H-hernioplasty: a tension-free repair for umbilical
     hernia. Br J Surg, 1995. 82(3): p. 371-2.
4.   Schumacher, O.P., et al., [Long-term results after Spitzy's umbilical
     hernia repair]. Chirurg, 2003. 74(1): p. 50-4.
5.   Luijendijk, R.W., et al., A comparison of suture repair with mesh repair
     for incisional hernia. N Engl J Med, 2000. 343(6): p. 392-8.
6.   Nyhus, L.M., Ubiquitous use of prosthetic mesh in inguinal hernia
     repair: the dilemma. Hernia, 2000(4): p. 184-186.
7.   Nyhus, L.M., Individualization of hernia repair: a new era. Surgery,
     1993. 114(1): p. 1-2.
8.   Kurzer, M., P.A. Belsham, and A.E. Kark, Tension-free mesh repair of
     umbilical hernia as a day case using local anaesthesia. Hernia, 2004.
     8(2): p. 104-7.
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     comparison of nylon, orlon, dacron, teflon, and marlex. AMA Arch Surg,
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                                                                             23
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     Tables

     Trial     Population Intervention Events                             Complications                 Follow-
                                                                                                        up
     Arroyo 200                 Suture hernia          Recurrence: Seroma/haematoma, Mean
     et al. consecutive         repair                 11/100      wound infection & follow-
     2001   patients                                   (11%)       other: 11%        up: 64
            diagnosed                                                                months
            with an             Mesh hernia            Recurrence: Seroma/haematoma, (range
            umbilical           repair                 1/100       wound infection & 21-80)
            hernia                                     (1%)        other: 10%
     Table 1: Trial comparing suture and mesh repair in umbilical hernia
     reconstruction


             Hernia size (cm)                 Number of patients                   Recurrence rate
                    1                                16                                 6.3%
                  1 - 1.9                               49                                  4.1%
                  2 - 2.9                               28                                 14.3%
                 3.0 - 3.9                               4                                 25.0%
                   ≥4                                   11                                 54.5%
     Table 2: Hernia size and recurrence (Schumacher, O.P., et al.) [4]


                   Page
CRF number                          Contents                                                     Parameters
                  number
1-
                             Informed consent

2-                                                      Physical examination   Description of hernia
                             Pre-operative workup       Quality of life        MOS SF-36 and EQ-5D (see CRF-6)
                                                                               Age, length/ weight, history, medication,
                                                        Demographics
                                                                               risk factors, ASA score
3-                                                                             Technical details of procedure (incision,
                                                                               size of the defect, use of drains), duration
                                                                               of procedure, complications during
                             Per-operative procedure
                                                                               procedure (including conversion to other
                             Randomisation
                                                                               procedure), thrombosis prophylaxis,
                                                                               intravenous antibiotics and method of
                                                                               anaesthesia
4-                                                      Wound inspection       Haematoma, seroma, infection
                                                        Pain score/use of      Daily VAS score (see CRF-7), use of
                             Post-operative             analgesics             analgesics
                             procedure
                                                        Complications          Re-operation
                                                        Drains                 Drain production
5-
2-3 weeks
3 months                     Follow-up                                         See follow-up assessments (table 5)
12 months
24 months
6-
inclusion                    MOS SF-36 and EQ-5D                               Quality of life
12 months

7-                                                                             Daily assessment (hospital/home)
                             VAS pain score
                                                                               Assesment after 3, 12 and 24 months
     Table 4: CRF overview



                                                                                                               25
                    Reherniation     Reoperation    MOS SF-36   Ultrasound   VAS pain
Follow up point
                    (exact date)     (exact date)   and EQ-5D    imaging      score
Inclusion         Not applicable   Not applicable      ×         None           ×
Post-operative
(days 1- 6)       Not applicable   Not applicable    None        None           ×
2 weeks          ×              ×          None                  None         None
3 months         ×              ×          None                  None           ×
12 months        ×              ×           ×                    None           ×
24 months        ×              ×          None                     ×           ×
Table 5: Overview of follow-up assessments




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