Efficacy of Ondansetron in LARS Treatment

This is a multi-centre randomized, double-blind, placebo-controlled, cross-over study aimed at testing the efficacy of Ondansetron in the low anterior resection syndrome (LARS) occurring as a consequence of surgery for rectal cancer.

Patients will be randomized (1:1 ratio) to receive either 4 weeks of Ondansetron followed by 4 weeks of placebo (O-P sequence) or 4 weeks of placebo followed by 4 weeks of Ondansetron (P-O sequence). Neither the investigator nor the patient will be aware of the sequence (O-P or P-O) assigned to the patient. One week will elapse between the end of the first treatment and start of the second treatment.

The hypothesis to be tested is that 4 weeks of oral Ondansetron at the dose of 4mg BID induce a variation of the LARS Score at least 7 points (20%) greater than the variation occurring after 4 weeks of placebo.

The sample size calculated for the primary analysis is 38 evaluable patients. Considering an expected attrition rate of about 20%, it is expected to enrol approximately 46 patients in total.

Inclusion criteria

• Age ≥ 18 years
• Patients willing and able to comply with the study procedures
• Female patients of childbearing potential must agree to use a reliable method of contraception
• Written informed consent Patients who have undergone low anterior resection (LAR) for rectal cancer in the last 2 years provided that at least 4 weeks have elapsed since recanalization and 4 weeks have elapsed since any chemo- and/or radiotherapy
• Presence of functioning anastomosis
• Presence of significant LARS symptoms assessed by LARS Score

Exclusion criteria

• Known hypersensitivity or allergy to Ondansetron
• Previous Ondansetron antiemetic therapy completed less than 4 weeks before study entry
• Antitumor chemotherapy or radiotherapy completed less than 4 weeks before study entry
• Congenital long Q-T syndrome
• Ongoing treatment with drugs causing prolongation of the Q-T interval
• Uncorrected hypokalemia or hypomagnesemia
• Women who are pregnant or breast feeding or are willing to become pregnant during the study
• Clinically significant concomitant disease states or anastomotic complications which could impair the ability of the patient to participate in the trial
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.