5-HT3 Antagonists (Antiemetics) and Cardiac Safety

5-HT3 Antagonists (Antiemetics) and Cardiac Safety Using an Active Surveillance Approach

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.

Study Overview

• Status: Completed
• Conditions: Adverse Reaction to Other Drugs and Medicines
• Intervention / Treatment: Drug: Ondansetron

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 Type: Observational
• Enrollment (Actual): 266

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Health Centre of British Columbia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children, women of a reproductive age, and pregnant women receiving ondansetron for treatment of post-operative or chemotherapy-induced nausea and vomiting or hyperemesis gravidarum.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric patients; Children <6 months to 18 years of age receiving ondansetron for management of: Post-operative nausea and vomiting; Chemotherapy-induced nausea and vomiting	Drug: Ondansetron; All patients will be receiving treatment with ondansetron as part of standard care.; Other Names: Zofran
Female patients; Pregnant patients or women of a reproductive age (18-45 years) receiving ondansetron for management of: Hyperemesis gravidarum; Post-operative nausea and vomiting	Drug: Ondansetron; All patients will be receiving treatment with ondansetron as part of standard care.; Other Names: Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identify clinical and genetic variants associated with ondansetron-induced prolongation of QT interval	Up to 2 years

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Bruce Carleton, PharmD., University of British Columbia

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ACTUAL): August 1, 2020
• Study Completion (ACTUAL): August 1, 2020

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (ESTIMATE): May 7, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: QT prolongation; Genomic biomarkers
• Additional Relevant MeSH Terms: 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: H13-02338