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

Trial Summary

What is the purpose of this trial?

"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.

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.

Is ondansetron safe for humans?

Ondansetron is generally considered safe for humans, with common side effects being headache and constipation. However, there have been reports of cardiovascular issues like atrial fibrillation and chest pain in some cases. ^{1 2 3 4 5}

How does the drug ondansetron differ from other treatments for atrial fibrillation?

Ondansetron is unique because it is primarily known as an antiemetic (prevents nausea and vomiting) and works by blocking 5-HT3 receptors, which is different from typical atrial fibrillation treatments that focus on heart rate and rhythm control. ^{6 7 8 9 10}

Research Team

James E Tisdale, PharmD

Principal Investigator

Purdue University

Eligibility Criteria

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 between 18 and 100 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Coronary vasospasm and atrial fibrillation associated with ondansetron therapy. [2014]

2. England pubmed.ncbi.nlm.nih.gov

The 5-HT3 receptor antagonist ondansetron re-establishes control in refractory emesis induced by non-cisplatin chemotherapy. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Safety of ondansetron. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor. [2019]

7. France 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. [2014]

8. Russia (Federation) 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]. [2015]

9. Poland pubmed.ncbi.nlm.nih.gov

Ondansetron as an effective drug in prophylaxis of chemotherapy--induced emesis in children. [2013]

10. Bulgaria pubmed.ncbi.nlm.nih.gov

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