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5-HT3 Antagonists (Antiemetics) and Cardiac Safety

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ClinicalTrials.gov Identifier: NCT02436798
Recruitment Status : Recruiting
First Posted : May 7, 2015
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Bruce Carleton, 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.

Condition or disease Intervention/treatment
Adverse Reaction to Other Drugs and Medicines 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
Estimated Enrollment : 250 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: 5-HT3 Antagonists (Antiemetics) and Cardiac Safety Using an Active Surveillance Approach
Study Start Date : June 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Pediatric patients

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

Female patients

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




Primary Outcome Measures :
  1. Identify clinical and genetic variants associated with ondansetron-induced prolongation of QT interval [ Time Frame: Up to 2 years ]

Biospecimen Retention:   Samples With DNA
DNA samples will be retained for genomic analyses.


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Ages Eligible for Study:   6 Months to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436798


Contacts
Contact: Bruce Carleton, PharmD. bcarleton@popi.ubc.ca

Locations
Canada, British Columbia
Children's and Women's Health Centre of British Columbia Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Bruce Carleton, PharmD.    604-875-2179    bcarleton@popi.ubc.ca   
Principal Investigator: Bruce Carleton, PharmD.         
Sponsors and Collaborators
University of British Columbia
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Bruce Carleton, PharmD. University of British Columbia

Responsible Party: Bruce Carleton, Director, Pharmaceutical Outcomes Programme, University of British Columbia
ClinicalTrials.gov Identifier: NCT02436798     History of Changes
Other Study ID Numbers: H13-02338
First Posted: May 7, 2015    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017

Keywords provided by Bruce Carleton, University of British Columbia:
QT prolongation
Genomic biomarkers

Additional relevant MeSH terms:
Ondansetron
Antiemetics
Serotonin 5-HT3 Receptor Antagonists
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents