Ondansetron for Low Anterior Resection Syndrome (LARS): A Double Blind, Placebo Controlled, Cross-Over, Randomized Study

Abstract

Abstract Background Low Anterior Resection Syndrome (LARS) after rectal resection is common and debilitating. Current management strategies include behavioural and dietary modifications, physiotherapy, antidiarrheal drugs, enemas and neuromodulation, but results are not always satisfactory. Aims This study examines the efficacity and safety of Ondansetron, a serotonin receptor antagonist, to treat patients with LARS. Methods This is a randomized, multi-centric, double-blinded, placebo-controlled, cross-over study. Patients with LARS (LARS score >20) no longer than 2 years after rectal resection were randomised to receive either 4 weeks of Ondansetron followed by 4 weeks of placebo (O-P group) or 4 weeks of placebo followed by 4 weeks of Ondansetron (P-O group). The primary endpoint was LARS severity measured using the LARS score; secondary endpoints were incontinence (Vaizey score) and quality of life (IBS-QoL questionnaire). Patients’ scores and questionnaires were completed at baseline and after each 4-week treatment period. Results Out of 46 randomized patients, 38 were included in the analysis. From baseline to the end of the first period, in the O-P group, the mean (SD) LARS score decreased by 25% (from 36.6 (5.6) to 27.3 (11.5)) and the proportion of patients with major LARS (score >30) went from 15/17 (88%) to 7/17 (41%), (p=0.001). In the P-O group, the mean (SD) LARS score decreased by 12% (from 37 (4.8) to 32.6 (9.1)), and the proportion of major LARS went from 19/21 (90%) to 16/21 (76%). After cross over, LARS scores deteriorated again in the O-P group receiving placebo, but further improved in the P-O group receiving Ondansetron. Mean Vaizey scores and IBS QoL scores followed a similar pattern. Conclusions Ondansetron should be included in the treatment algorithms of LARS after low anterior resection for rectal cancer because it is a safe and simple treatment that appears to improve both symptoms and quality of life.