The STITCH trial has been designed as a prospective, multicenter, double-blind, randomized controlled trial, in which the large bites technique will be compared with the small bites technique.
Patients scheduled for an elective abdominal operation through a midline incision will be asked for informed consent at the outpatient clinic or in hospital on the day preceding the day of surgery. Also, emergency laparotomies can be included in this trial if the patient is able to sign the informed consent. We intend to investigate the efficacy of the small bites technique in all risk groups. This also includes oncological gynaecological patients in centers with at least 50 median laparotomies a year.
• Signed informed consent
• Laparotomy through a midline incision
• Age 18 years or older
• Previous incisional hernia or fascial dehiscence with secondary healing after a midline incision
• Abdominal surgery through a midline incision within the last three months
Since the STITCH trial is an intervention study, it is not considered desirable to combine this trial with other intervention studies. In case of non-intervention (registration) studies, it will be judged on individual basis whether it is suitable and ethically correct to include a patient in both the STITCH trial and in another study. Patients will be included in the STITCH trial in combination with one other trial (registration trials only), provided that it is possible to organize the informed consent and the follow up in a proper way for the individual patient for both trials.
Included patient are registrated before surgery in an online data base (designed and managed by HOVON data center, Rotterdam, the Netherlands,) after signed informed consent via the Internet via TOP (Trial Online Process; see http://www.stitchtrial.nl
). The patient namecode, date of birth, name of caller, name of responsible physician, sex and eligible criteria will be registered. Every participating institution has its own login code.
The randomization process is started only 15 minutes before closure to prevent consequences due to the trial during the operation with the online TOP randomisation.
Patients will be randomized between closure with the large tissue bites technique or with the small tissue bites technique. Randomisation is stratified by center, and between surgeon or resident with a minimization procedure, ensuring balance within each stratum and overall balance. The randomization result will be given immediately by TOP. A confirmation email without randomization result will be send to the investigator.
Patients will be kept unaware of the type of closure until the endpoint of the trial. Surgeons or residents blinded for the procedure will perform out patient clinic controls. Postoperative ultrasonography will be performed by radiologists blinded for type of closure. The randomisation procedure, blinding and objectification of incisional hernia by ultrasound will provide the best possible data to support preference for the large bites technique or the small bites technique over the other for closure of the abdominal wall.
In this trial the large bites technique will be compared with the small tissue bites technique as developed in Sundsvall Hospital, Sweden [18
]. In the first group, the conventional large bites technique will be applied with bite widths of 1 cm and intersuture spacing of 1 cm with the use of one PDS plus II loop with a 48 mm needle. In the second group, the small bites technique will be applied with bite widths of 0,5 cm and intersuture spacing of 0,5 cm with the use of PDS plus II 2-0 with a 31 mm needle. In the small bites technique, twice as many stitches will be placed per sutured cm, with a smaller needle and thinner suture material. In the Swedish hospital where the small bites techniques has been in use for many years, this combination proved the easiest and safest method to perform the small bites technique [18
In both groups wound length is measured before closing of the fascia. After measument of the woundlength, the number of stitches is calculated. In the large bites technique at least one suture per cm wound length must be placed. In the small bites technique at least two sutures per cm wound length must be placed. The number of stitches is counted by the assistant during closure.
In both arms, suturing is initiated at both ends of the incision towards the middle where an overlap will be created of at least 2 cm. The remaining sutures will be measured and the suture length used for closure of the fascia and the SL:WL ratio will be calculated by the scrub nurse. In both arms, suture length to wound length ratios (SL:WL) of 4:1 are aimed at.
In every hospital the OR nurses the surgeons or gynecologists and residents are instructed before the start of the trial in the individual institution during presentations and demonstration movies. During at least the first five inclusions the study coordinator will be present in the OR before randomization to assist randomization and control the correct applying of the standardized techniques. For every included patient a form with the detailed closing protocol is added to the clinical chart. Only when the surgeon is familiar with both the techniques, the nurses with the counting and measuring of the stitches and suture material and the study, centers are allowed to run the trial. Also, for every included patient a form with the detailed closing protocol is added to the clinical chart. During the study unplanned audits are performed to control quality.
• Primary outcome will be incisional hernia occurrence within one year after surgery, either clinically and/or ultrasonographically detected.
• Postoperative complications
• Quality of life
• Cost effectiveness
We use the definition of the incisional hernia by the European Hernia Society: 'any abdominal wall gap with or without bulge in the area of a postoperative scar perceptible or palpable by clinical examination or imaging'. The classification made by the European Hernia Society is used [35
]. The classification of incisional hernias: Incisional hernias will be classified according to their localization, size, reducibility and symptoms.
Discharge dates and complications will be registered. Patients who fail to keep their annual clinic appointment will be given the option of a further appointment at a more suitable date or a visit to their home if they cannot make it to the outpatient clinic. The following data will be gathered at different points in time:
• Date of birth
• Length and weight
• Current smoker (Yes or No)
• Medical history (including chronic obstructive pulmonary disease (COPD), diabetes mellitus, cardiac disease, prior laparotomies)
• Preoperative radiotherapy or chemotherapy
• Preoperative or perioperative corticosteroids
• Previous abdominal operations
• Other abdominal wall hernias
• American Society of Anaesthesiologists (ASA) classification
• Width of linea alba (if preoperative Computed Tomography Imaging is available)
• Type of operation
• Suture length: wound length ratio
• Number of stitches
• Length of incision
• Closure time
• Blood loss
• Operation time
• Antibiotic prophylaxis
• Drains and location
• Thrombosis prophylaxis
• Pain medication
• Peroperative complications (intestinal lesions, bleeding, other)
• Epidural catheter
• Blood transfusion
• Postoperative ventilation and duration
• Postoperative corticosteroids
• Postoperative radiation therapy
• Postoperative pain medication
• Postoperative ileus and duration
• Postoperative complications:
○ Centers for Disease Control criteria for Surgical Site Infection, according to the guidelines proposed by Mangram in 1999 [36
] Appendix 1.
○ Wound haematoma: accumulation of blood in the wound area, which warrants surgical exploration and intervention.
○ Pulmonary infections
○ Ventilation problems
○ Re-admission and indication
○ VAS pain score until day 6 post operative
At 1 and 12 months, ultrasound imaging will be performed to examine the midline for any asymptomatic clinically not detectable incisional hernias. Size and location of any incisional hernias will be registered.
Outpatient clinic follow up
• Outpatient clinic visit at 1 and 12 months
○ Incisional hernia
○ Wound infection
○ Seroma formation
○ Other wound problems
○ Other abdominal wall hernia
• Ultrasound at 1 and 12 months
• VAS pain scores and Quality of Life forms preoperatively (day of operation or the day before) and at 1,3, 6 and 12 months
During the 1 month and 1 year follow up an ultra sound examination will be performed to measure the distance between the rectus muscles at 3 point in the incision and check for incisional hernia. A specific score is used for the ultrasound examination. At ten points, which include 4 measurements of the distance between the rectus muscle, the quality of the scar in the abdominal wall is objectified. With this method the conclusion if there is an incisional hernia can also be made on the score list. In this list is controlled for:
An intact linea alba?
Bulging without Valsalva manouvre?
Bulging with Valsalva manouvre?
Distance between rectus muscles in scar on 1/3 cranial part in cm?
Distance between rectus muscles in scar on 1/3 caudal part in cm?
Maximum distance between rectus muscles in scar in cm?
Maximum distance between rectus muscles at place of bulging or defect in cm?
Is there a defect? If yes, the size of the defect and location
Is there fatty tissue in the defect?
Is there a bowel loop in the defect?
The radiologist is asked to make prints of every measurement and finding.
Quality of life will be assessed based on standardized Quality of Life forms including the EuroQol-5D and Short Form-36 before and at 1 month, 3 months, 6 months, and 12 months after surgery.
We will perform an ex-post economic evaluation in which a new suture technique using small bites is compared with the traditionally applied large bites technique, from a societal perspective. The economic evaluation will be performed in accordance with Dutch guidelines (Oostenbrink, 2004).
To measure the economic impact of the new suture technique using small bites the cost-effectiveness will be assessed by calculating the incremental cost-effectiveness ratio, defined here as the difference in average costs between both suture techniques divided by the difference in average effects. The primary outcome measure will be the costs per reduced incisional hernia within 1 year. Secondary, a cost-utility analysis will be performed using costs per quality adjusted life year (QALY) as outcome measure, using the EQ-5D.
Costs for all separate actions and time used by all individual health care professionals, and all other materials will be measured from a societal perspective for both bites techniques, which means that both direct medical costs (e.g. intervention costs, intramural and extramural medical costs) and indirect costs (absence from work, patient costs) will be included in the analysis.
For the most important cost items, unit prices will be determined by following the micro-costing method (Gold et al, 1996), which is based on a detailed inventory and measurement of all resources used. Resource costs arise within the hospital and consist of outpatient visits, inpatient days, use of the operation room, radiology examinations, blood tests, etc. Real medical costs will be calculated by multiplying the volumes of health care use with the corresponding unit prices. For instance, the calculation of the costs of both suture techniques will consist of detailed measurement of investments in manpower, equipment, materials, housing and overhead. The salary schemes of hospitals and other health care suppliers will be used to estimate costs per hour for each health care professional. Taxes, social securities and vacations will be included.
Data on effects (reduction of incisional hernia), costs (time costs of new suture technique and material and development costs) and savings (reduced health care use of patients without incisional hernia) will all be collected in this study. Data on treatment (hospitalisation) and follow-up consultations will be collected retrospectively from (electronic) patient charts and hospital administration. This data will be collected by health care professionals using a data-collection form. Information will collected on:
- length of hospital stay
- length of stay in ICU
Data on extramural care, work absence and other patient costs will be gathered via questionnaires at each follow-up (1 and 12 months).
For a description of the calculation of the effect measures see paragraph 'outcome parameters'.
Discounting of future costs and effects is not relevant because of the limited time horizon of 1 year. When costs of a treatment are similar across subgroups, the absolute benefit determines the cost-effectiveness of a treatment for a specific subgroup.
Randomized controlled trials are designed to evaluate the effects of treatment at the group level, and cost-effectiveness is usually calculated for this group as a whole. There could however be substantial and relevant between subgroup variability. It is therefore common to consider subgroup specific effects of interventions. The subgroup specific cost-effectiveness will be estimated by first deriving a prognostic index, based on the predefined predictors of incisional hernia: abdominal aneurysm aorta (AAA), obesity, diabetes, COPD, corticosteroid usage, radiotherapy, cardiovascular disease, smoking, age, cancer, other abdominal wall hernias and collagen disorders.
Sample size calculation
Millbourn et al. found a decrease in the incidence of incisional hernia from 18% to 5,6% in a randomized controlled trial [34
]. In this trial, follow-up consisted of clinical instead of radiological examination for incisional hernia occurrence. In this trial, ultrasound examination will be used in order to be able to diagnose incisional hernia with higher sensitivity. It is expected that a relative decrease of the incidence incisional hernia after one year of 50% is reasonable. The mean reported one year incidence of incisional hernia in literature is 15%[1
]. In order to reduce the mean incidence of incisional hernia from 15 to 7.5%, power calculations showed that two groups of 259 evaluable patients each are needed (power = 0.80, alfa = 0.05). Loss to follow-up is estimated at 10% of included patients. A total of 576 patients (2 × 288) will be included in the study to correct for loss to follow-up. Overall effects will be calculated adjusted for predictive baseline characteristics, which will lead to a higher statistical power.
Descriptive statistics will include median and interquartile range for continuous variables, and absolute numbers (with %) for categorical variables. Randomized groups will be compared for imbalance without formal statistical testing. Analysis will be by intention-to-treat. Differences between randomized groups will be tested with appropriate statistical methods, including t-tests or Mann-Whitney tests for continuous variables (considering whether the normality assumption is rejected by the Kolmogorov-Smirnov test with Lilliefors correction test), and chi-square tests for categorical variables. The primary outcome (incisional hernia) will be analyzed with Kaplan-Meier analysis and a Cox regression analysis, to adjust for any loss to follow up between 30 days and 1 year after surgery. The primary analysis is a covariate adjusted Cox model, which includes the following predefined, well-establihed predictors of incisional hernia: abdominal aneurysm aorta (AAA), obesity, diabetes, corticosteroid usage, radiotherapy, COPD, smoking, age, cancer, inguinal hernia, cardiovascular disease and collagen disorders.
Subgroup effects will be assessed by tests of interaction to prevent overinterpretation of apparent differences in effectiveness. Quality of life data will be analyzed by paired T-tests, comparing baseline with follow-up measurements, and repeated measures analysis. A two-sided p < 0.05 will be taken to indicate statistical significance.
The Erasmus University Medical center is the sponsor of this trial. Adverse events are defined as any undesirable experience occurring to a subject during a clinical trial, whether or not considered related to the investigational intervention. All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death; is life threatening (at the time of the event); requires hospitalization or prolongation of existing inpatients' hospitalization; results in persistent or significant disability or incapacity; is a new event of the trial likely to affect the safety of the subjects, such as an unexpected outcome of an adverse reaction, major safety finding from a newly completed animal study, etc. All SAEs will be reported to the accredited Medical Ethical Committee (MEC) that approved the protocol, according to the requirements of that MEC. Serious Adverse events are death and burst abdomen. Adverse Events are readmission and reoperations.
An independent data and safety monitoring committee will evaluate the progress of the trial and will examine safety parameters every 3 months. The committee can unblind the data whenever deemed necessary based on reported adverse events. All involved physicians will repetitively be asked to report any potential adverse events caused by the study protocol. These adverse events will be listed and discussed with the monitoring committee. The monitoring committee can ask for a full report in order to discuss a specific adverse event. A copy of this report will be sent to the central ethics board and to the involved physicians. All deceased patients will be evaluated by the safety committee for cause of death and possible trial related serious adverse effects. Every death will be reported to the central ethics board and the local ethics board. The Data Safety Monitoring Board will consist of an epidemiologist/statistician and two independent surgeons.
This study will be conducted in accordance with the principles of the Declaration of Helsinki and 'good clinical practice' guidelines. The Medical Ethical Committee of the Erasmus University Medical Center Rotterdam has approved the protocol. The Ethical Committees of the participating centers are applied for local feasibility. Prior to randomization, written informed consent will be obtained from all patients.