Ondansetron for Atrial Fibrillation

Recruiting at 2 trial locations

Overseen By Tanner Sergesketter, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Indiana University

Must be taking: Anticoagulants

Must not be taking: Serotonergic drugs, QTc-prolonging drugs

Disqualifiers: Childbearing potential, Syncope, Thyrotoxicosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ondansetron, a drug typically used to prevent nausea, can aid individuals with atrial fibrillation (Afib), a condition characterized by an irregular heartbeat. Researchers aim to determine if ondansetron can reduce the duration of Afib episodes and slow the heart rate during these episodes. Participants will be divided into two groups: one receiving ondansetron and the other receiving a placebo (a sugar pill) for comparison. This trial suits individuals with Afib who are scheduled for an ablation procedure and are already on blood thinners as recommended. As a Phase 4 trial, this research seeks to understand how an FDA-approved and effective treatment can further benefit patients with Afib.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are on certain medications like QTc-prolonging drugs (except amiodarone and propafenone) or serotonergic drugs. It's best to discuss your current medications with the trial team to see if they are allowed.

What is the safety track record for ondansetron?

Research shows that ondansetron, a drug often used to prevent nausea and vomiting, can sometimes affect heart rhythm. Some reports have found that it can cause unusual changes in the heart's electrical activity, potentially leading to dangerous heart rhythms. For example, one case involved a person developing atrial fibrillation, an irregular heartbeat, after taking ondansetron.

On the positive side, other studies have found benefits. In one study with very sick patients, those who took ondansetron had lower death rates in the hospital compared to those who didn't take it. This suggests that while there are risks, ondansetron might be helpful in certain situations.

The FDA has approved ondansetron for treating nausea and vomiting, indicating it has been tested for safety in those cases. However, its use for atrial fibrillation is still under study, and possible heart-related side effects should be considered. Always consult a healthcare provider to understand the risks and benefits for specific health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for atrial fibrillation, which often include medications like beta-blockers, calcium channel blockers, and anticoagulants, ondansetron is unique because it's primarily known as an anti-nausea medication. Researchers are excited because ondansetron acts on serotonin receptors, which might help stabilize heart rhythms in a novel way. This approach could offer a new pathway for managing atrial fibrillation, potentially with fewer side effects than traditional drugs.

What evidence suggests that ondansetron might be an effective treatment for Afib?

This trial will compare the effects of ondansetron with a placebo in patients with atrial fibrillation scheduled for AF ablation. Research suggests that ondansetron might help manage atrial fibrillation (Afib), an irregular heartbeat. Studies have shown that ondansetron blocks a specific electrical signal in the heart, potentially involved in Afib. Blocking this signal could reduce the duration of Afib episodes and slow the heart rate during these episodes. While ondansetron primarily prevents nausea, recent findings indicate it could also benefit the heart. However, some reports mention that ondansetron might cause abnormal heart rhythms, so potential risks must be considered. Overall, evidence suggests ondansetron could be promising for treating Afib, but further research is needed. ^{1 2 3 5 6}

Who Is on the Research Team?

James E Tisdale, PharmD

Principal Investigator

Purdue University

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-100 with persistent atrial fibrillation (Afib) needing electric shock treatment, on recommended blood thinners unless exempt. Excluded are pregnant women, those with recent syncope or thyrotoxicosis, reversible noncardiac Afib causes, contraindicated anticoagulation use, recent heart surgery, certain drug therapies including serotonergic drugs and QTc-prolonging medications.

Inclusion Criteria

I have a heart rhythm problem that needs treatment to correct it.

I am on blood thinners as recommended, unless my risk score allows skipping it.

Exclusion Criteria

I have been diagnosed with an overactive thyroid.

I have the most severe form of heart failure.

I have been diagnosed with low blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ondansetron 8 mg orally twice daily or placebo for 28 days

4 weeks

Continuous ECG monitoring with 2 visits for ECG patch application

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ondansetron
• Placebo

Trial Overview

The study tests if Ondansetron can stop Afib before scheduled electric shocks to restore normal rhythm or reduce its duration over a month. Participants will randomly receive either Ondansetron or a placebo without knowing which one they're taking. The effect on heart rate during Afib will also be observed.

How Is the Trial Designed?

Group I: Ondansetron Experimental Treatment 1 Intervention

Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with ondansetron 8 mg orally twice daily for 28 days (n=40)

Group II: Placebo Placebo Group 1 Intervention

Patients with atrial fibrillation scheduled to undergo AF ablation will receive treatment with matching placebo orally twice daily for 28 days (n=40)

Ondansetron is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Zofran for:

• Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy
• Prevention of postoperative nausea and/or vomiting

Approved in European Union as Zofran for:

• Prevention of nausea and vomiting associated with chemotherapy
• Prevention of postoperative nausea and vomiting

Approved in Canada as Zofran for:

• Prevention of nausea and vomiting associated with chemotherapy
• Prevention of postoperative nausea and vomiting

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Purdue University

Collaborator

Trials

239

Recruited

72,200+

Published Research Related to This Trial

Ondansetron is an effective antiemetic that works by selectively inhibiting the 5-HT3 serotonin receptor, showing equal or superior efficacy compared to the traditional antiemetic metoclopramide, especially against nausea from cisplatin and other highly emetogenic drugs.

It is generally well tolerated with few adverse effects, such as headache and gastrointestinal issues, and does not cause extrapyramidal reactions, making it a safe option for preventing nausea and vomiting during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron: a serotonin receptor (5-HT3) antagonist for antineoplastic chemotherapy-induced nausea and vomiting. Kohler, DR., Goldspiel, BR.[2019]

Ondansetron has been shown to be safe and well-tolerated in approximately 1,400 cancer patients and 650 other volunteers, with the main side effects being mild constipation and headache.

The drug has a wide therapeutic index, does not interact with commonly prescribed medications, and has no reported dependence or extrapyramidal side effects, making it a reliable option for anti-emetic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ondansetron. Smith, RN.[2013]

In a double-blind, placebo-controlled study of 20 patients with cerebellar tremor, ondansetron significantly improved performance on a writing task, with 13 out of 19 patients showing improvement compared to their baseline.

Patients also reported functional improvement in their tremor after receiving ondansetron, with 12 out of 20 feeling better, while none reported improvement with the placebo, indicating potential efficacy of ondansetron for tremor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor. Rice, GP., Lesaux, J., Vandervoort, P., et al.[2019]

A 51-year-old male developed serious cardiovascular issues, including new-onset atrial fibrillation and ST segment elevation, after receiving intravenous ondansetron during surgery, highlighting potential cardiovascular risks associated with this medication.

This case, along with other reports, suggests that ondansetron and similar 5-HT3 receptor antagonists may cause significant cardiac adverse effects, prompting the need for clinicians to monitor patients for electrocardiographic changes when administering these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary vasospasm and atrial fibrillation associated with ondansetron therapy. Havrilla, PL., Kane-Gill, SL., Verrico, MM., et al.[2014]

In a study involving 12 college students, the serotonin (5-HT3) receptor antagonists ondansetron and granisetron significantly reduced the occurrence of gastric tachyarrhythmia during motion sickness compared to a placebo.

Despite their effectiveness in reducing gastric dysrhythmias, ondansetron and granisetron did not prevent the onset of nausea or other motion sickness symptoms, indicating that while they may help with gastric stability, they are not effective anti-nausea treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness. Levine, ME., Chillas, JC., Stern, RM., et al.[2015]

In a pilot study of 20 patients with acute unilateral vestibular neuritis, ondansetron treatment resulted in a significantly lower early caloric vestibular deficit compared to metoclopramide, suggesting it may be more effective in managing vestibular symptoms.

Patients receiving ondansetron also experienced shorter hospital stays and quicker times to independent walking, indicating that it not only helps with symptoms but may also improve recovery times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protective effect of 5-HT3 antagonist against vestibular deficit? Metoclopramide versus ondansetron at the early stage of vestibular neuritis: a pilot study. Venail, F., Biboulet, R., Mondain, M., et al.[2014]

In a study of 40 patients with advanced tumors receiving various chemotherapy regimens, ondansetron demonstrated a strong prophylactic antiemetic effect, particularly in the CHOP group, where 64% experienced full control of nausea and vomiting.

No significant side effects were reported from ondansetron treatment, indicating it is a safe option for managing chemotherapy-induced nausea and loss of appetite in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Novel pharmacologic form of ondansetron (Zofran)--lingual tablets in the prevention of cytostatic chemotherapy-induced loss of appetite, nausea and vomiting]. Gershanovich, ML., Beresneva, IA., Makhnova, EV.[2015]

In a clinical trial involving 20 patients, Ondansetron (Zofran) effectively prevented the Bezold-Jarisch reflex-like reaction during anesthesia, demonstrating its potency as a 5HT3 antagonist.

The study supports the use of Ondansetron in anesthesiology, as it was administered safely and monitored various physiological parameters without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of ondansetron as a drug for premedication. Kamenova, E.[2013]

Ondansetron effectively controlled acute emesis in 53% of patients on a specific dosing schedule after non-cisplatin-based chemotherapy, demonstrating its potential as a treatment for those previously resistant to standard antiemetics.

The drug maintained its antiemetic efficacy across multiple treatment cycles, with no major toxicity reported, making it a safe option for patients experiencing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 5-HT3 receptor antagonist ondansetron re-establishes control in refractory emesis induced by non-cisplatin chemotherapy. Seynaeve, C., de Mulder, PH., Lane-Allman, E., et al.[2019]

In a study of 35 children undergoing highly emetogenic chemotherapy, ondansetron was found to be highly effective in preventing nausea and vomiting, achieving complete or major responses in 85.3% of patients without cisplatin and 71.4% with cisplatin, compared to only 38.8% with traditional antiemetics.

Ondansetron was administered at lower than recommended doses for 85 days without any adverse effects, indicating it is a safe and effective antiemetic option, especially since it does not cause sedation and was well-received by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron as an effective drug in prophylaxis of chemotherapy--induced emesis in children. Kołecki, P., Wachowiak, J., Beshari, SE.[2013]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05844501

Ondansetron for the Management of Atrial Fibrillation

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 ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10198140/

Effects of ondansetron treatment on outcomes of critically ill ...

Early use of OND in critically ill patients with MI may exert protective effects by reducing in-hospital mortality and 28- and 90-day mortality.

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fda.gov

fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-abnormal-heart-rhythms-may-be-associated-use-zofran-ondansetron

Abnormal heart rhythms may be associated with use of ...

Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal ...

4.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/497166

Ondansetron for the Management of Atrial Fibrillation

The investigators have found that ondansetron blocks IKas, and the investigators think that this means that ondansetron may work well to treat ...

5.

journals.lww.com

journals.lww.com/iaaf/fulltext/2016/17020/ondansetron_induced_atrial_fibrillation_.6.aspx

Ondansetron-induced atrial fibrillation?

We report a case in which new onset atrial fibrillation occurred possibly with the use of ondansetron in a 76 yr old male patient.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/24314899/

Ondansetron and the risk of cardiac arrhythmias

Eligible cases described a documented (or perceived) arrhythmia within 24 hours of ondansetron administration. The primary outcome was arrhythmia occurrence ...