5-HT3 Antagonists (Antiemetics) and Cardiac Safety

Completed

• Conditions: Adverse Reaction to Other Drugs and Medicines
• Interventions: Drug: Ondansetron

• Registration Number: NCT02436798
• Lead Sponsor: University of British Columbia

Brief Summary

5-HT3 antagonists (ondansetron) are highly effective medications for the treatment of nausea and vomiting. However, these medications also associated with potentially severe and life-threatening cardiac adverse drug reactions (ADRs), particularly QT prolongation. Data regarding the cardiac safety and inter-individual variability in cardiac effects of ondansetron when used in vulnerable populations such as children and pregnant women are very limited. The results of this study will enable better-informed therapeutic decision-making regarding the use of ondansetron in children and pregnant women, with the overall goal to improve the safety of these commonly used antiemetic medications. Furthermore, predictive pharmacogenetic markers of severe 5-HT3 antagonist toxicity could be used to identify patients at risk of cardiac toxicity before the drug is administered.

Detailed Description

The specific objectives are to:

1. Determine and compare the cardiac safety profile of ondansetron in children, when used for prevention and management of post-operative nausea and vomiting and chemotherapy induced nausea and vomiting. Identify clinical factors including pre-existing cardiac conditions or physiological conditions that predispose to ventricular arrhythmias, concomitant cardiotoxic chemotherapy or concomitant volatile anaesthetic agents and investigate their impact on cardiac adverse effects of ondansetron.

2. Determine and compare the cardiac safety profile of ondansetron when used in pregnant women or women of a reproductive age for the treatment of hyperemesis gravidarum or post-operative nausea and vomiting. Identify clinical factors including pre-existing cardiac conditions or physiological conditions, which predispose to ventricular arrhythmias that may support implementation of risk mitigation actions.

3. Identify genetic variants associated with 5-HT3 antagonist-induced prolongation of QT interval.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-05-04
• Study First Posted: 2015-05-07
• Primary Completion: 2020-08
• Study Completion: 2020-08
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-13
• Last Update Posted: 2021-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 266

Inclusion Criteria

1. Children 6 months - 18 years of age who are being treated with ondansetron for prevention and management of post-operative nausea and vomiting and chemotherapy-induced nausea and vomiting.
2. Pregnant women and women of a reproductive age (18-45 years of age) who are being treated with ondansetron for hyperemesis gravidarum or postoperative nausea and vomiting.

Exclusion Criteria

1. Patients with congenital long QT syndrome.
2. Subjects who do not speak and understand English.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Female patients	Ondansetron	Pregnant patients or women of a reproductive age (18-45 years) receiving ondansetron for management of: 1. Hyperemesis gravidarum 2. Post-operative nausea and vomiting
Pediatric patients	Ondansetron	Children \<6 months to 18 years of age receiving ondansetron for management of: 1. Post-operative nausea and vomiting 2. Chemotherapy-induced nausea and vomiting

Primary Outcome Measures

Name	Time	Method
Identify clinical and genetic variants associated with ondansetron-induced prolongation of QT interval	Up to 2 years

Trial Locations

Locations (1)

Children's and Women's Health Centre of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada