Clinical trial NCT03182179: Efficacy of Ondansetron in LARS Treatment
Official title: Efficacy of Ondansetron in the Treatment of Low Anterior Resection Syndrome (LARS): a Multi-centre, Randomized, Double Blind, Placebo-controlled Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rectal Cancer
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
First posted: 2017-06-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in LARS score
timeFrame: 10 wks
Secondary outcomes:
measure: Vaizey (St. Mark's) score
timeFrame: 10 wks
measure: Irritable Bowel Syndrome-Quality of Life
timeFrame: 10 wks
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: CHUV
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano, Civico e Italiano
Study officials:
affiliation: Ospedale Regionale di Lugano, Civico e Italiano
name: Dimitri Christoforidis, Prof.
role: STUDY_DIRECTOR
References: