Study objective
The Stoma-Const trial is a randomised trial comparing three different surgical procedures for the construction of a colostomy.
Endpoints
The primary endpoint is the presence of parastomal hernia as detected by clinical examination or CT scan at 12 months after surgery. A bulge in the vicinity of the stoma is not sufficient in this study to define a parastomal hernia. If there is any doubt in the clinical setting, the patients must be examined by a CT scan in a prone position. Secondary endpoints include: re-admission rate, postoperative complications (classified according to Clavien-Dindo [27]), stoma-related complications (registered in the case record form (CRF) at Stoma Care nurse follow-up), total length of hospital stay during 12 months, health-related quality of life and health economic analysis, re-operation rate, mortality within 30 days and 12 months of primary surgery. Re-admissions and re-operations as registered in the hospitals’ databases at 24 months to ascertain that possible long-term complications related to the stoma construction are identified.
Inclusion criteria
Patients are eligible if the following conditions are met:
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the patient is presenting with a condition for which an elective surgical procedure is planned including formation of a colostomy
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it is possible to operate on the patient in regard to concomitant disease
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the patient has given informed consent to participate
Exclusion criteria
External validity
All patients with a condition for which an elective surgical procedure is planned including a colostomy formation, and who are not included and randomised, will be registered in the ‘screening log’ at each participating centre including information on date, hospital, gender, age, ASA classification and type of operation. The reason for non-inclusion or exclusion is noted.
Randomisation
All participating patients give written informed consent. After inclusion no changes are made in the planning for the operation. The patient will be randomised to one of the three groups of intervention during surgery in the operating theatre directly prior to the stoma formation (Figure 1). Randomisation will be performed by blocks of closed envelope systems in each participating hospital. It will be balanced and stratified by hospital. Laparoscopic as well as open procedures will be included and, although not stratified by open or laparoscopic procedures, their use will be noted in the CRF.
Including hospitals may choose to randomise between all three techniques or two of them. This decision is made before the hospital enters the study. The blocks will be set up according to this system, and the total number of 80 patients in each group will be managed through this system.
When patients are not subject to the treatment modality as randomised, data will be analysed on an ‘intention-to-treat basis’ (once randomised, patients will not be excluded or change groups because of conversion or type of surgery). Patients who do not consent to participation or are excluded will be treated by cross incision in the fascia as the usual routine.
Surgical procedure
A stoma care nurse marks all stoma sites preoperatively. At the time of the stoma formation, randomisation to one of the three (or in applicable cases two) procedures is made. The centre point of the preoperatively marked place for the stoma is lifted and a circular skin incision is performed. Blunt or ‘semi-blunt’ dissection is used through the subcutaneous tissue, using a step-wise downwards movement with retractors assisted by sharp dissection as needed. When the ventral fascia of the rectus abdominis has been reached, dissection is stopped. A disposable, sterile measurement tape is used in the open surgical procedures, and the metric scale on the laparoscopic stapler is used in laparoscopic surgical procedures. The depth of the subcutaneous fat is measured. The width of the left colon together with its mesocolon is measured at the point where it will pass through the fascia (the depth of the subcutaneous fat + 20-30 mm). The fascia incision is calculated using this measurement - circular incision in the fascia with a diameter equalling 50% of the width of the patient’s left colon with mesocolon, or a cruciate incision where the arms measure one-half of the width of the patient’s left colon with mesocolon. If it is apparent that the incision will be too large, it may be reduced, but measured thoroughly and noted in the operative CRF. The muscular fibres are separated bluntly.
Stoma formation without a mesh
The dorsal fascia is opened. The proximal colon end is taken through the stoma incision (plica epiploicae may be removed, if necessary). Care is taken to ensure adequate circulation to the colon involved in the stoma. If the width of the incision is insufficient for adequate circulation, a widening should be performed, measured and noted in the CRF. The muco-cutaneous suturing is made using 4-0 absorbable interrupted sutures, three-point sutures (mucosa, muscular layer and skin) starting with one in each quadrant and adding ordinary muco-cutaneous sutures in between as needed. The height of the stoma after it is created should be at least 1 cm.
Stoma formation with a mesh
The incision in the fascia is performed with a cruciate incision, with size according to the measurements described above, and the mesh will be placed using the sublay technique as previously described [14]. A fine-thread, large-pore lightweight polypropylene monofilament mesh measuring 10 × 10 cm is used. The mesh is placed dorsal to the rectus abdominis muscle and anterior to the posterior rectus fascia by dissection through either midline in open surgery or by blunt dissection under the rectus abdominis muscle in laparoscopic surgery. A cruciate incision with a size measured according to the instructions above is made in the anterior sheath of the fascia and in the mesh. The bowel is brought out through a cross-cut in the centre of the mesh where the arms should measure one-half of the width of the patient’s left colon and its mesocolon. If the width of the incision is not sufficient, a widening should be performed, measured and noted in the CRF. Stitches fix the lateral corners of the mesh to the posterior rectus sheath. The medial corners of the mesh are grasped with a stitch of the running suture closing the midline incision during open surgery, and this is not applicable to laparoscopic procedures.
The diameter of the stoma is measured immediately after the operation.
Postoperative treatment
Local guidelines are followed and must be applied equally in all three (in applicable cases, two) groups, without any systematic differences. Any postoperative treatment with antibiotics must be noted in the CRF, including reasons and total treatment time. This applies to both systemic as well as oral antibiotics. All postoperative information regarding stoma and stoma function will be given according to local routines.
Follow-up
The follow-up during the postoperative hospital stay is recorded in a CRF. Time until full oral feeding is resumed and time until first gas and stool are registered.
Patients will be clinically examined at 6 (5–7) months and at 12 (11–13) months postoperatively and further as needed (suspected parastomal herniation), by a surgeon (not one of the colorectal team) preferably specialised in hernia surgery, to diagnose a possible parastomal hernia. At 12 months patients for whom no clinical parastomal herniation has been found will undergo a CT examination of the abdomen (wall), performed in prone position [25], which also will be part of the routine 12 months follow-up by abdomen CT for colorectal cancer patients. A study-specific standardised referral to abdomen CT is used, and although the study is not blinded, no information as to type of stoma construction is included. All radiologic departments use a specific protocol for this part of the abdomen CT.
Stoma height, diameter, colour, skin irritation and bandaging problems are documented by nurses specialised in stoma care during hospitalisation and at 4-6 weeks, 6 months and 12 months and are registered in a CRF.
Quality of life
All patients are asked to fill out questionnaires preoperatively, at 6 months and at 12 months after discharge from the hospital. The questionnaire has been constructed using previously used questions [28] that have been developed through a process of in-depth qualitative interviews and content validated by an expert panel consisting of colorectal surgeons, stoma care nurses and nurses specialised in surgery. The questionnaire was face-to-face validated by patients with a surgical procedure including a colostomy as well as patients with an existing colostomy using the validation methods described previously for a questionnaire for prostate cancer patients (26).
Health economic evaluation
A health economic analysis will be performed based on the information collected in the CRF together with information from the hospital registries, based on the model presented by Bjöholt et al.[29]. The model will be used in combination with sensitivity calculations.
Data collecting and monitoring
An operative CRF including reasons for surgery, planned operation and patient data, together with measurements from the surgical procedure is filled in for the operation (by the surgeon). For the hospitalisation period a nurse at the ward will complete a CRF, and for each follow-up visit a surgeon and a nurse will complete a CRF.
The postoperative questionnaires will be given to the patients by the stoma therapist. All data will be kept within University of Gothenburg and Sahlgrenska University Hospital systems using inherent security systems. A logistic database with complete patient ID will be used and kept within a separate IT system from the result database with all study information. Security measures will include one to maximum two users of this database, with unique usernames and personal login, as well as automatic throw-out. The questionnaires filled out by the patients are returned to the trial coordinating centre, SSORG, at Sahlgrenska University Hospital. The finalised database based on trial number and without patient ID, will be kept within another IT system than the logistic database.
Statistical analysis
The Swedish trial on the effect of prophylactic net placement has reported 50% incidence of parastomal hernia without mesh [14]. Our own data on abdominoperineal excision from Sahlgrenska University Hospital indicate an incidence of 25% [28]. The power calculation based on available information has used the hypothesis that the cruciate incisional stoma formation, performed as described here, should result in parastomal hernia incidence of 30% and the circular incision or prophylactic mesh reinforcement could reduce this incidence to 10% each. An 80% power and a 5% level of significance with a two-sided alternative hypothesis would require 62 patients per group using a chi-square test. Expecting 20% drop-outs, 80 patients will be recruited in each group.
The primary analysis will be based on the full analysis set. This analysis set is designed to be consistent with recommendations set forth in International Conference on Harmonisation (ICH) guidance document E9: Statistical Principles for Clinical Trials, and is intended to adhere as closely as practically possible to the intention-to-treat (ITT) principle. The full analysis set will consist of all randomised patients who had surgery and who contributed with any follow-up data.
Patients will be analysed according to randomised procedure. A sensitivity analysis evaluating the actual procedure will be made for the most important outcomes.
All hypothesis testing will be conducted using two-sided tests, and P values ≤ 0.05 after rounding will be considered statistically significant. A pair-wise comparison between the experimental arms and the control arm will be performed and the significance level will be corrected using the Bonferroni-Holm method. Event-type variables (yes or no) will be compared between randomised procedures using chi-square tests, and relative risks and risk differences will be estimated. Where appropriate, the time to event will be described using Kaplan-Meier plots. The number of events of a certain type (for example, number of complications or re-operations) will be analysed using Poisson regression with randomised procedure as a factor and time under observation as an offset variable.
Total length of hospital stay will be compared between groups using Wilcoxon’s rank-sum test. Sub-group analyses specifically looking at the following groups of patients will be performed:
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a)
BMI >30 kg/m2
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b)
Immunosuppression
Sensitivity analyses will be performed for the primary variable and selected secondary variables, as deemed appropriate, where groups are compared pair-wise utilising only data from centres where both treatments were allocated.
Exploratory analyses (such as logistic regression) may be performed to investigate the influence of background factors (patient characteristics, perioperative factors) on outcomes.
Participating hospitals
The study will recruit patients from hospitals in Denmark and Sweden.
Approvals and registration
The trial has been approved by the Swedish Ethical Committee (EPN/Göteborg Dnr 547-12) and the Swedish radiotherapy protection committee (Dnr 12-38). It has been approved by the Danish ethics committee (Protocol H-4-2013-061), and by the Danish Data Protection Agency (no. HEH-2013-049, I-Suite no:02418). The study was registered at http://www.clinicaltrials.gov (NCT NCT01694238) prior to inclusion of the first patient.
