Official Title
5-HT3 Antagonists (Antiemetics) and Cardiac Safety Using an Active Surveillance Approach
Brief Title
5-HT3 Antagonists (Antiemetics) and Cardiac Safety
Protocol ID
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.
Enrollment Count
266 participants
Eligibility Criteria
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.
Filters
Adverse Reaction to Other Drugs and Medicines
COMPLETED
CHILD
ADULT