Ondansetron for the Management of Atrial Fibrillation

February 2, 2026 updated by: James E. Tisdale, Indiana University

Inhibition of Small Conductance Calcium-Activated Potassium Current: A New Therapeutic Approach for Atrial Fibrillation

"Afib" is a common irregular heartbeat. Afib can cause stroke, blood clots, dementia and death. Medicines used to treat Afib often do not work well and can cause serious side effects. Clinicians need medicines that work better for Afib. Medicines for Afib work by blocking a current in the heart called a potassium current. There is a newer potassium current called IKas that can contribute to Afib. A medicine called ondansetron is used to keep people with cancer from getting sick to their stomach and throwing up. The investigators have found that ondansetron blocks IKas, and the investigators think that this means that ondansetron may work well to treat Afib. So, in this study the investigators want to find out if ondansetron can: 1) Reduce the amount of time that people have Afib, and 2) Slow down the heart rate when people have Afib. The investigators will study 80 people who are scheduled to have an AF ablation. Several weeks prior to undergoing the ablation procedure, these AF patients will be assigned by chance (like flipping a coin) to one of two groups: ondansetron 8 mg by mouth twice daily or a sugar pill (placebo), which they will take for 28 days. The people in the study will not know whether they are receiving ondansetron or placebo. The investigators will find out if ondansetron reduces the percentage of time that people are in Afib. Also, the investigators will find out if ondansetron slows the heart rate while people are having Afib. The investigators will compare the people in the study who take ondansetron with the people in the study who take placebo. This research will help the investigators to find out if ondansetron can be used as a medicine for people who have Afib.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Atrial fibrillation (AF) is a common arrhythmia associated with symptoms, stroke, systemic embolism, heart failure, dementia, and mortality. Guideline-recommended strategies for conversion to and maintenance of sinus rhythm (SR) and ventricular rate (VR) control are of limited efficacy and/or are poorly tolerated. There is a critical need for safer, more effective alternatives for AF drug therapy. The apamin-sensitive small-conductance calcium-activated potassium (SK) ion current (IKas) is important for repolarization in the atria and pulmonary vein muscle sleeves. IKas also contributes to sinoatrial and AV node electrophysiology. Therefore, IKas may be a target for rhythm and rate control in AF. Evidence suggests: 1) IKas plays an important role in the mechanism of AF, 2) The antiemetic agent ondansetron at therapeutic concentrations is a potent IKas inhibitor, and 3) Ondansetron is a cardiac-selective IKas inhibitor. Thus, the investigators hypothesize that ondansetron is effective for rhythm and rate control in patients with AF. Specific Aim 1: Determine the efficacy and safety of ondansetron for reducing AF burden. This aim will be achieved via a prospective, randomized, double-blind placebo-controlled study in patients with AF (n=80). Patients with AF scheduled to undergo an elective catheter AF ablation (pulmonary vein isolation) will be randomized in double-blind fashion to receive ondansetron 8 mg twice daily (n=40) or matching placebo (n=40) for 28 days. The study drug/placebo will be initiated several weeks prior to the ablation procedure, and the 28 days of treatment will be complete at least 3 days prior to the ablation. Continuous ECG recording will be performed using 2 consecutive adhesive skin patch ECG monitors, which provide 14-days of continuous recording. The primary outcome measure will be AF burden (percentage of time in AF). Specific Aim 2: Determine the efficacy and safety of ondansetron for VR control in AF. The effect of ondansetron versus placebo on VR control will be assessed. Primary outcome measures will be mean daily heart rates in AF on days 7, 14, 21 and 28 days following initiation of ondansetron/placebo.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana Clinical Research Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • James E Tisdale, BSc, PharmD
        • Sub-Investigator:
          • Heather Jaynes, MSN
        • Sub-Investigator:
          • Richard J Kovacs, MD
        • Sub-Investigator:
          • Fatimah Alhurayri, PharmD, MS
      • Indianapolis, Indiana, United States, 46202
        • Not yet recruiting
        • Indiana University Health Methodist Hospital
        • Sub-Investigator:
          • Heather Jaynes, MSN
        • Contact:
        • Sub-Investigator:
          • Elisabeth von der Lohe, MD
        • Sub-Investigator:
          • Ronald Mastouri, MD
        • Principal Investigator:
          • James E Tisdale, PharmD
        • Sub-Investigator:
          • Fatimah Alhurayri, PharmD, MS
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Purdue University
        • Principal Investigator:
          • James E Tisdale, BSc, PharmD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Heather A Jaynes, MSN
        • Sub-Investigator:
          • Fatimah Alhurayri, PharmD, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women 18-100 years of age
  • ECG-verified AF and/or atrial flutter requiring elective catheter ablation
  • Receiving guideline-recommended anticoagulation (if CHA2DS2-VASc score is 0 (men) or 1 (women), anticoagulation can be omitted)

Exclusion Criteria:

  • Women of childbearing potential
  • Subject reported syncope of unknown origin within the previous 6 months
  • Diagnosis of active thyrotoxicosis
  • Diagnosis AF from reversible noncardiac causes
  • Diagnosis of acutely decompensated heart failure

  • Left ventricular ejection fraction less than or equal to 20%

    • New York Heart Association class IV heart failure
    • Diagnosis of severe liver disease (Child-Pugh score greater than or equal to 10)
  • Cardiac surgery (preceding 2 months)
  • Not receiving anticoagulation due to contraindications (as determined by treating physician and recorded in the medical record)
  • Pretreatment QRS > 180 ms, QTc > 450 ms within two weeks of screening visit
  • Heart rate < 50 beats per minute in SR
  • Diagnosis of hypotension
  • Diagnosis of Wolff-Parkinson-White syndrome
  • Previous ondansetron hypersensitivity or serotonin syndrome
  • Diagnosis of phenylketonuria
  • Diagnosis of congenital long QT syndrome
  • Concomitant therapy with both beta-blockers and a nondihydropyridine CCB
  • History of drug-induced torsades de pointes or QTc prolongation
  • Concomitant therapy with QTc-prolonging medications (www.crediblemeds.org), except amiodarone and propafenone
  • Concomitant therapy with serotonergic drugs (selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, lithium, tramadol), apomorphine, phenytoin, carbamazepine, oxcarbazepine, rifampin.
  • Left ventricular ejection fraction < 20% and those with NYHA class IV heart failure with reduced ejection fraction (confirmed by diagnosis or echocardiogram within 6 months of enrollment in screening)
  • Patients with pre-existing allergies to adhesives
  • Patients with neuromuscular stimulators

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ondansetron
Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with ondansetron 8 mg orally twice daily for 28 days (n=40)
Drug: Ondansetron 8mg
Ondansetron 8 mg orally twice daily for 28 days
Placebo Comparator: Placebo
Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with matching placebo orally twice daily for 28 days (n=40)
Drug: Placebo
Matched placebo orally twice daily for 28 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Atrial fibrillation burden
Time Frame: Total duration of study (28 days)
Burden of atrial fibrillation, defined as overall percentage of time in atrial fibrillation.
Total duration of study (28 days)
Ventricular rate control
Time Frame: 7 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
7 days after initiation of ondansetron/placebo
Ventricular rate control
Time Frame: 14 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
14 days after initiation of ondansetron/placebo
Ventricular rate control
Time Frame: 21 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
21 days after initiation of ondansetron/placebo
Ventricular rate control
Time Frame: 28 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
28 days after initiation of ondansetron/placebo

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients in sinus rhythm
Time Frame: 28 days after initiation of ondansetron/placebo
Proportion of patients in sinus rhythm at 28 days after initiation of ondansetron/placebo
28 days after initiation of ondansetron/placebo
Time to atrial fibrillation recurrence
Time Frame: 28 days after scheduled electrical cardioversion
Time to atrial fibrillation recurrence after electrical cardioversion
28 days after scheduled electrical cardioversion
Adverse effects
Time Frame: During the 28 days of treatment with ondansetron or placebo
Adverse effects associated with ondansetron or placebo
During the 28 days of treatment with ondansetron or placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indiana University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
American Heart Association
Purdue University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James E Tisdale, PharmD, Purdue University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 22, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 6, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16581
  • 22TPA964193 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Data will become available upon publication of study results in clinical trials.gov. Data will be available indefinitely

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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