The Therapeutic Role of Gastrografin for Treating Small Bowel Obstruction in Children: A Multi-Centre Canadian Prospective Study

This will be a 2-year multi-centre clustered open-label clinical trial examining the therapeutic use of a drug called Gastrografin in reducing the length of hospital stay, time to feeding, and rate of surgery in children with a small bowel obstruction. Each participating centre will select which of the two treatment options they will offer to patients at their centre. The patients at each centre will be aware of the treatment offered at thier centre before making the decision whether to participate in the study. The two arms of the study are: Gastrografin or Control (saline solution). If a patient declines participation in the arm offered at their centre they will not be enrolled in the study. The investigators have chosen an open-label cluster study design instead of a randomized controlled trial (RCT) because it is common for RCTs to be stopped early due to poor recruitment rates within paediatric surgery. A 2018 systematic review reported that of the 137 eligible RCTs within paediatric general surgery only 19% successfully achieved the projected recruitment number and further, only 53% of studies that provided an expected completion date achieved the target. Based on the power calculation for this study, the investigators require a total of 146 patients (73 in each group) to achieve 80% power. Therefore if a RCT design is used, estimating a typically recruitment rate of 40-50%, it would take over 8 years to reach the required sample size between the participating centres. With a prospective, open-label design, the investigators anticipate the total number of possible patients that can be approached to participate in the study across all centres to be between 152-160 patients over the two years. The investigators estimate large centres will on average recruit between 10-12 patients per year, medium centres 6-8 patients per year, and small centres 2-4 patients per year.

Consent/Assent will be obtained from the parents/caregivers prior to participation in the study. Assent, in addition to parental/caregiver consent, will be used for patients between the ages of 7 and 11. Prior to the patient participating in any study-related activities, consent will be obtained. Patients will be included in this study if they are between the ages of 6 months and 18 years of age, are diagnosed with a small bowel obstruction, and have undergone 24 hours of monitoring and non-surgical management. Patients will be excluded from the study if they have thyroid stimulating hormone or thyroxine levels outside of the normal range, are taking any thyroid replacement medication, have previously had thyroid surgery, have an allergy to the medical or non-medical ingredients in Gastrografin, and weigh less than 10kg at the time of diagnosis.

Recruitment will begin following a positive diagnosis of a small bowel obstruction secondary to previous surgery, assessment by the surgical team, and after the patient has been admitted to the hospital for a twenty-four hour period of non-surgical management, which includes nasogastric (NG) decompression, fluid resuscitation, and maintenance. The patients will be assessed by the surgical team on a regular basis during this time as part of standard care and enrollment in the study does not preclude urgent or emergent surgical intervention. After 24 hours of admission, the patient will be approached to participate in the study. The study will be explained to the patient and their parents/caregivers by the research team. The patient and their family will be given as much time as required to talk among themselves about the study and ask any questions about the study to the research team. Depending on which study arm is offered at their hospital, they will either receive one dose of saline solution via their NG tube plus non-surgical management (Control arm) or one dose of Gastrografin via their NG tube plus non-surgical management (Gastrografin arm). At any point during the study if the patient's clinical condition changes and the surgical team thinks the patient needs an operation then it will occur regardless of enrollment in the study.

Prior to the patient receiving Gastrografin or saline solution, the investigators will confirm that the patient does not have an allergy to iodine, as Gastrografin contains high levels of iodine, and that they have normal thyroid hormone levels. The investigators will test the patient's levels of thyroxine (T4) and thyroid stimulating hormone (TSH) by blood draw, as excessive iodine exposure can block thyroid hormone synthesis in young children. The investigators will be able to test thyroid hormone levels from the patients initial blood work at admission, which occurs as part of the patient's standard care. This way there will be no delay in the treatment of the small bowel obstruction (SBO) due to waiting for lab results and the patient can receive either treatment at 24 hours post admission. Thyroid hormone levels will be tested throughout the study for the Gastrografin group from routine blood draws that are part of standard care when a patient is NPO. Therefore no additional blood draws will be required as part of the study. If the patient's thyroid hormone levels are normal they can be enrolled in the study. If not, they will not be eligible to participate in the study.

Twenty-four hours following admission and consent, patients will either receive Gastrografin or an equivalent volume of saline (Control arm) via the NG tube, depending on the arm offered at their centre. In both cases, the NG tube will be clamped for 30 minutes to one hour. Doses of Gastrografin will be proportional to the patient's age and will be based on the recommendations from the manufacturer (i.e., product monograph) and published studies. Dosages will range from 30ml for children up to 5 year of age to 60ml for children between 5-18 years and will not be diluted. The manufacturer only recommends diluting Gastrografin if the patient is of low-birth weight or is considered debilitated. Since none of the patient recruited for this study will meet these criteria, Gastrografin will not be diluted. Patients who do not receive Gastrografin will receive an equivalent volume of saline solution via the NG tube in addition to non-surgical management, which includes NG tube decompression, NPO, and IV fluids. At this time (24 hours post admission) an x-ray will be completed for both study arms.