Ondansetron and the QT Interval In Adult Emergency Department Patients

The purpose of this study is to assess the use of the medication ondansetron (zofran) in the emergency department. There are studies of the ability of ondansetron to cause a prolongation in the QT interval (a certain measurement on an EKG) in anesthesia and cancer patients, but not on emergency department patients. This is an observational study where patients that are going to receive the anti-nausea medicine ondansetron in the emergency department will have an EKG performed every 2 minutes for 20 minutes to determine if the QT interval prolongs and returns to normal in that time period. Any serious outcomes will be reported. There is expected to be no adverse outcomes from this routinely used medication.

Study Overview

• Status: Completed
• Conditions: Ondansetron
• Intervention / Treatment: Drug: Ondansetron

Detailed Description

Intravenous ondansetron is routinely used in adult emergency department patients experiencing nausea or vomiting. The FDA has changed the drug label to warn of prolongation of the QT interval and required the manufacturer to perform additional studies. There are rare case reports of cardiac electrical toxicity to include QT prolongation, atrial fibrillation, severe bradycardia, ventricular tachycardia, supraventricular tachycardia, and the potential for Torsades de Pointes. All of the reported literature on ondansetron comes from post-operative patients, patients receiving chemotherapy, and healthy volunteers, but has never been assessed in the emergency department population. Adult emergency department patients that do not meet the exclusion criteria will be enrolled prior to receiving intravenous ondansetron. Administration of ondansetron will be at the discretion of the attending physician. A twelve-lead electrocardiogram (EKG) or 12-lead rhythm strip will be generated prior to drug administration, and every 2 minutes following drug administration for 20 minutes after administration. During the entire 20 minutes the patient will be on a cardiac monitor and if any of the defined adverse cardiac electrical events occur (non-sinus rhythm, severe bradycardia, sudden cardiac death) the patient will be treated using standard Advanced Cardiac Life Support methods and admitted for continued monitoring. The mean maximal QTc prolongation (as measured by the Bazett formula), as well as the rate of adverse cardiac events with 95% confidence intervals will be reported.

The global objective of this study is to determine if routine use of intravenous ondansetron in the emergency department is associated with cardiac risks. The primary objective is to determine the mean maximal prolongation in QTc interval from baseline as measured by the Bazett formula. The secondary objective is to determine the number of severe adverse cardiac electrical events (non-sinus rhythm, severe bradycardia, sudden cardiac death) associated with routine use of intravenous ondansetron in the adult emergency department patient.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • Texas
    • Fort Hood, Texas, United States, 78544
      • Carl R Darnall Army Medical Center
  • Washington
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The target population is adult (>18 years old) emergency department patients who have been deemed appropriate to receive intravenous ondansetron.

Description

Inclusion Criteria:

• Age >18
• Patient to receive 4mg of intravenous ondansetron

Exclusion Criteria:

• Age <18
• known long QT syndrome
• received oral or intravenous ondansetron within 4 hours of enrollment
• co-administration of any known QT prolonging agents
• QTc on baseline of >450 ms for males and >470ms for females
• allergy or known hypersensitivity to ondansetron
• altered mental status
• non-sinus rhythm on baseline EKG
• hypokalemia (as defined by the lower limit of normal for the reference laboratory)
• hypomagnesemia (as defined by the lower limit of normal for the reference laboratory)
• any presentation for chest pain with signs of ischemia on baseline EKG
• QRS duration > 120 msec
• bundle branch block (right or left)
• ventricular pre-excitation or signs of left ventricular hypertrophy with repolarization abnormalities

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IV Ondansetron; Adult emergency department patients receiving 4mg of IV ondansetron as part of their treatment plan.	Drug: Ondansetron; 4mg of intravenous ondansetron; Other Names: Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QTc Interval With Ondansetron Administration	The primary objective is to determine the mean maximal prolongation in QTc interval from baseline as measured by the Bazett formula. A baseline EKG will be obtained and then after drug administration an EKG will be performed every 2 minutes until 20 minutes has passed. The mean maximal QTc change will be calculated.	Baseline to 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	The secondary objective is to determine the number of severe adverse cardiac electrical events (non-sinus rhythm, severe bradycardia, sudden cardiac death) associated with routine use of intravenous ondansetron in the adult emergency department patient. All of these outcomes will be recorded for each patient during the emergency department stay which could range from 20 minutes to several hours.	20 minutes to 8 hours

Collaborators and Investigators

• Sponsor: C.R.Darnall Army Medical Center
• Collaborators: Madigan Army Medical Center
• Investigators: Principal Investigator: Peter M Moffett, MD, Carl R Darnall Army Medical Center Department of Emergency Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 29, 2012
• First Submitted That Met QC Criteria: December 29, 2012
• First Posted (Estimate): January 3, 2013

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Ondansetron; QT interval; QTc; QT prolongation; Drug induced QT prolongation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies; 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: 375393