Low anterior resection syndrome following rectal cancer treatment Digestive System Postprocedural complications and disorders of the digestive system
Conditions
Interventions
Eligible patients will be randomised (at a ratio of 1:1) to receive either ondansetron or matching placebo
the dose of ondansetron will be between 4-24 mg daily for 6 weeks. Dose titration will be undertaken in the first two weeks of the study to optimise the dose and avoid constipation. Treatment will be
LARS score at baseline (minor 21-29, major =30)
and loperamide use over the 14 day baseline period (0 days, 1-6 days, =7 days).
The treatment period is 6 weeks and participants will be asked to complete a daily diary (online or paper option will b
Sponsors
Nottingham University Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged =18 years 2. Previously undergone standard total mesorectal excision (TME) resection with, or without, neoadjuvant chemoradiotherapy (CRT) for pT0-4, N0-2, M0 rectal cancer 3. =1 year after the end of any chemoradiotherapy and surgical treatment (ileostomy closure or primary resection if a stoma was not performed) 4. No evidence of rectal cancer recurrence 5. LARS questionnaire symptom score of =21 (minor or major LARS) 6. LARS symptoms to include both of the following: 6.1. Presence of =4 bowel movements per day on average during the 14 days prior to the baseline visit 6.2. Moderate, severe or very severe faecal urgency (unable to delay bowel movements by 10 min or more) on =4 days during the 14 days prior to the baseline visit 7. LARS symptoms not adequately controlled by current treatment 7. For participants of childbearing potential, or their partners, agreement to use medically accepted contraception (e.g. oral contraceptive and condom, Intra-uterine device (IUD) and condom, or diaphragm with spermicide and condom) for the duration of study treatment and for at least 30 days afterwards for women, and 90 days afterwards for men. 8. Able to read and understand questionnaires in English 9. Written informed consent provided
Exclusion criteria
Exclusion criteria: 1. Clinical and radiological anastomotic leakage after rectal cancer surgery, defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments 2. Gastrectomy 3. Other known organic GI diseases (e.g. Crohn’s disease, ulcerative colitis, coeliac disease) 4. Untreated thyroid dysfunction 5. Taking other medications influencing colonic motility (e.g. opioids, cholinergic agents, prokinetics, metoclopramide, cisapride, etc.) which are likely to be stopped or changed during the course of the trial 6. Lactose intolerance 7. Known QTc interval =450 ms for men and =470 ms for women 8. Continuous use of ondansetron for >1 month within the past year 9. Contraindications to ondansetron (e.g. concomitant use with apomorphine, hypersensitivity to any component of the preparation, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption) 10. Currently participating in any interventional phase of another clinical trial 11. Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of days with no or mild urgency over the last 14 days of the planned 6 week treatment period measured using participant report in a daily diary between baseline and 6 weeks. Participants will record whether or not they had a bowel movement with urgency that day (yes or no), and those who responded yes will score their most urgent bowel movement that day as one of the following: mild (time able to delay bowel movement =10 mins), moderate (time able to delay bowel movement =5 to <10 mins), severe (time able to delay bowel movement =1 to <5 mins), or very severe (time able to delay bowel movement <1 min). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Bowel dysfunction following a low anterior resection measured using the Low Anterior Resection Syndrome (LARS) questionnaire at 6 weeks 2. Bowel dysfunction score measured using the Memorial Sloan-Kettering Cancer Center (MSKCC) questionnaire at 6 weeks 3. Quality of life measured using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) questionnaire and the EuroQol 5-dimension 5-level (EQ-5D-5L) questionnaire at 6 weeks 4. Psychological status measured using the Hospital Anxiety and Depression Scale (HADS) at 6 weeks 5. Anxiety measured using the anxiety subscale of the HADS at 6 weeks 6. Depression measured using the depression subscale of the HADS at 6 weeks 7. Percentage of participants with =30% improvement from baseline in the percentage of days with urgency for =50% of the days of the planned 6 week treatment period (“Urgency responders”) measured using participant report of urgency in a daily diary between baseline and 6 weeks. Participants will record whether or not they had a bowel movement with urgency that day (yes or no), and those who responded yes will score their most urgent bowel movement that day as one of the following: mild (time able to delay bowel movement =10 mins), moderate (time able to delay bowel movement =5 to <10 mins), severe (time able to delay bowel movement =1 to <5 mins), or very severe (time able to delay bowel movement <1 min). 8. Percentage of participants with =50% improvement from baseline in the percentage of days with any stool consistency of 6 or 7 on the Bristol Stool Form Scale (BSFS) for more than 50% of the days of the planned 6 week treatment period (“Stool consistency responders”) measured using participant report using the BSFS in a daily diary between baseline and 6 weeks. 9. Number of stools per day over the last 14 days of the planned 6 week treatment period measured using participant report of stool frequency in a daily diary between baseline and 6 weeks 10. Number of episode | — |
Countries
England, United Kingdom
Contacts
Public ContactAlison Lloyd
Outcome results
None listed