5-HT3 Antagonists (Antiemetics) and Cardiac Safety

Adverse Reaction to Other Drugs and Medicines Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02436798
• Other study ID #: H13-02338
• Status: Completed
• Start date: June 2014
• Est. completion date: August 2020

Study information

• Verified date: May 2021
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adverse Reaction to Other Drugs and Medicines

Intervention

Drug:
• Ondansetron
All patients will be receiving treatment with ondansetron as part of standard care.

Locations

Country	Name	City	State
Canada	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identify clinical and genetic variants associated with ondansetron-induced prolongation of QT interval		Up to 2 years