Efficacy of Ondansetron in LARS Treatment (Hodolar)

Efficacy of Ondansetron in the Treatment of Low Anterior Resection Syndrome (LARS): a Multi-centre, Randomized, Double Blind, Placebo-controlled Crossover Study

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). It will be one week of washout between the two treatments.

During the treatment questionnaires will be completed by the patients to evaluate the efficacy of the study treatment and the quality of live.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Ondansetron 4 MG; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1011
    • CHUV
  • Lugano, Switzerland, 6900
    • Ospedale Regionale di Lugano, Civico e Italiano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: O-P sequence; Patients will receive of oral Ondansetron 4mg BD for 28 days followed by 28 days of placebo. It will be one week of washout between the two treatments.	Drug: Ondansetron 4 MG; Ondansetron is taken orally BD; Drug: Placebo; Placebo is taken orally BD
Experimental: P-O sequence; Patients will receive oral placebo for 28 days followed by Ondansetron 4mg BD for 28 days. It will be one week of washout between the two treatments.	Drug: Ondansetron 4 MG; Ondansetron is taken orally BD; Drug: Placebo; Placebo is taken orally BD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LARS score	The primary outcome is the change in LARS Score assessed before and after Ondansetron and placebo treatment	10 wks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaizey (St. Mark's) score	Change in Vaizey (St. Mark's) Score assessed before and at the end of Ondansetron and placebo treatment	10 wks
Irritable Bowel Syndrome-Quality of Life	Irritable Bowel Syndrome-Quality of Life (IBS-QoL) assessed before and at the end of Ondansetron and placebo treatment	10 wks

Collaborators and Investigators

• Sponsor: Ente Ospedaliero Cantonale, Bellinzona
• Investigators: Study Director: Dimitri Christoforidis, Prof., Ospedale Regionale di Lugano, Civico e Italiano

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): November 19, 2021
• Study Completion (Actual): November 19, 2021

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 8, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: ORL-CHIR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No