Clinical trial NCT02436798: 5-HT3 Antagonists (Antiemetics) and Cardiac Safety
Official title: 5-HT3 Antagonists (Antiemetics) and Cardiac Safety Using an Active Surveillance Approach
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adverse Reaction to Other Drugs and Medicines
Keywords: QT prolongation
Genomic biomarkers
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2015-05-07
Enrollment: 266
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Identify clinical and genetic variants associated with ondansetron-induced prolongation of QT interval
timeFrame: Up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Bruce Carleton, PharmD.
role: PRINCIPAL_INVESTIGATOR
References: