Atrial FibrillationPhase 4NCT05844501
Ondansetron for the Management of Atrial Fibrillation
A Phase 4 study testing Ondansetron 8mg in people with Atrial Fibrillation, run by Indiana University at 3 sites in United States.
Trial summary
"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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Ondansetron 8mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 Apr 2025to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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%
Show all 24Show fewer
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Heather Jaynes, MSN contact
United States3 sites, 3 recruiting
- Recruiting
Indiana Clinical Research Center
Indianapolis, Indiana, 46202
Scott Denne, MD, 317-274-4920, sdenne@iupui.edu
Sharon Cromer, 317-278-3446, scromer2@iupui.edu
- Not yet recruiting
Indiana University Health Methodist Hospital
Indianapolis, Indiana, 46202
Richard J Kovacs, MD, 317-274-0907, rikovacs@iu.edu
Elisabeth von der Lohe, MD
- Recruiting
Purdue University
Indianapolis, Indiana, 46202
James E Tisdale, BSc, PharmD, 317-880-5418, jtisdale@purdue.edu
Heather Jaynes, MSN, 317-847-2094, hwroblew@iu.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Atrial Fibrillation
- Being tested
- Ondansetron 8mg, Placebo
- Keywords
- Randomized, Placebo-controlled, Ondansetron, Arrhythmias, Atrial fibrillation
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ondansetron 8mgDrug
Ondansetron 8 mg orally twice daily for 28 days
PlaceboDrug
Matched placebo orally twice daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron | Experimental | Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with ondansetron 8 mg orally twice daily for 28 days (n=40) Receives: Drug: Ondansetron 8mg |
| Placebo | Placebo comparator | Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with matching placebo orally twice daily for 28 days (n=40) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Atrial fibrillation burden
Burden of atrial fibrillation, defined as overall percentage of time in atrial fibrillation.
Measured: Total duration of study (28 days)
Ventricular rate control
Maximum heart rate while in atrial fibrillation
Measured: 7 days after initiation of ondansetron/placebo
Ventricular rate control
Maximum heart rate while in atrial fibrillation
Measured: 14 days after initiation of ondansetron/placebo
Ventricular rate control
Maximum heart rate while in atrial fibrillation
Measured: 21 days after initiation of ondansetron/placebo
Ventricular rate control
Maximum heart rate while in atrial fibrillation
Measured: 28 days after initiation of ondansetron/placebo
Secondary outcomes (3)
Proportion of patients in sinus rhythm
Proportion of patients in sinus rhythm at 28 days after initiation of ondansetron/placebo
Measured: 28 days after initiation of ondansetron/placebo
Time to atrial fibrillation recurrence
Time to atrial fibrillation recurrence after electrical cardioversion
Measured: 28 days after scheduled electrical cardioversion
Adverse effects
Adverse effects associated with ondansetron or placebo
Measured: During the 28 days of treatment with ondansetron or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start22 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, Purdue University
- Responsible party
- Principal investigator, James E. Tisdale, Indiana University
- Investigators
- James E Tisdale, PharmD, Principal investigator, Purdue University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05844501
- Sponsor's protocol ID
- 16581
- Other IDs
- 22TPA964193
- Status last verified
- Feb 2026
- First submitted
- 13 Apr 2023
- Last updated
- 4 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibition of Small Conductance Calcium-Activated Potassium Current: A New Therapeutic Approach for Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT05844501
- Acronym / sponsor ID
- 16581
- Conditions
- Atrial Fibrillation
- Keywords
- Randomized, Placebo-controlled, Ondansetron, Arrhythmias, Atrial fibrillation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, Purdue University
- Study start
- 22 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 6 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ondansetron | Experimental | Drug: Ondansetron 8mgPatients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with ondansetron 8 mg orally twice daily for 28 days (n=40) |
| Placebo | Placebo comparator | Drug: PlaceboPatients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with matching placebo orally twice daily for 28 days (n=40) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ondansetron 8mgOndansetron 8 mg orally twice daily for 28 days | Drug | Ondansetron |
| PlaceboMatched placebo orally twice daily for 28 days | Drug | Placebo |
Primary outcome
Atrial fibrillation burden
Time frame: Total duration of study (28 days)
Burden of atrial fibrillation, defined as overall percentage of time in atrial fibrillation.
Ventricular rate control
Time frame: 7 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
Ventricular rate control
Time frame: 14 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
Ventricular rate control
Time frame: 21 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
Ventricular rate control
Time frame: 28 days after initiation of ondansetron/placebo
Maximum heart rate while in atrial fibrillation
3 secondary outcomes
Proportion of patients in sinus rhythm
Time frame: 28 days after initiation of ondansetron/placebo
Time to atrial fibrillation recurrence
Time frame: 28 days after scheduled electrical cardioversion
Adverse effects
Time frame: During the 28 days of treatment with ondansetron or placebo
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Individual participant dataSharing planned: Yes
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Heather Jaynes, MSN contact
James E Tisdale, PharmD principal investigator
Purdue University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ondansetron 8mg in people with Atrial Fibrillation, run by Indiana University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact James E Tisdale, PharmD (317-880-5418, jtisdale@purdue.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atrial fibrillation burden (time frame: Total duration of study (28 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.