Ondansetron for Atrial Fibrillation
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
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
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?
How does the drug ondansetron differ from other treatments for atrial fibrillation?
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.
See 20 more
Trial 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 (Serotonin 5-HT3 Receptor Antagonist)
- Placebo (Other)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: OndansetronExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana Clinical Research CenterIndianapolis, IN
Purdue UniversityIndianapolis, IN
Indiana University Health Methodist HospitalIndianapolis, IN
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Who Is Running the Clinical Trial?
Indiana UniversityLead Sponsor
American Heart AssociationCollaborator
Purdue UniversityCollaborator
References
Coronary vasospasm and atrial fibrillation associated with ondansetron therapy. [2014]To provide further evidence of cardiovascular adverse effects of ondansetron, including new-onset atrial fibrillation, ST segment elevation, and chest pain subsequent to ondansetron administration, and to review cardiovascular adverse events related to several 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists.
The 5-HT3 receptor antagonist ondansetron re-establishes control in refractory emesis induced by non-cisplatin chemotherapy. [2019]The efficacy and safety of two dose schedules of the 5-HT3 antagonist ondansetron (Zofran) were studied in 35 patients (group A: 19 patients, group B: 16 patients) previously refractory to standard antiemetics after non-cisplatin-based chemotherapy (greater than 5 emetic episodes). The maintenance of the antiemetic efficacy of ondansetron was further studied in 28 patients (13 A, 15 B) in respectively 36 and 48 retreatment courses. Ondansetron was administered as an 8 mg loading dose (A: 4 mg i.v. + 4 mg orally; B: 8 mg i.v.), followed by oral treatment for 5 days (A: 6-hourly; B: 8 mg 8-hourly). In the first treatment cycle acute emesis was completely controlled in 53% of the patients in group A and in 50% of the patients in group B. Delayed emesis was absent in 75% and 38% of the patients in group A and B respectively. In a second treatment cycle acute antiemetic control was achieved in 54% and 53% of the patients in group A and B respectively. Over the third and fourth subsequent treatments, complete control occurred in 56% and 38% of the patients in group A, and in 46% and 56% of the patients in group B respectively. Delayed emesis did not occur over the following courses in 62%, 89% and 75% of the patients on regimen A, in 57%, 60% and 63% of the patients on regimen B. The observed adverse effects were headache (37%) and constipation (42%). No extrapyramidal reactions were seen. Ondansetron is able to re-establish an acceptable antiemetic control in previously refractory patients on non-cisplatin-based chemotherapy, without major toxicity. This efficacy is maintained over the three following retreatment courses.
The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness. [2015]The purpose of this study was to determine the effects of the serotonin (5-HT3) receptor-antagonist antiemetics ondansetron and granisetron on the development of gastric tachyarrhythmia, nausea, and other symptoms of motion sickness.
Ondansetron: a serotonin receptor (5-HT3) antagonist for antineoplastic chemotherapy-induced nausea and vomiting. [2019]Ondansetron represents a new class of drugs that exert their antiemetic activity by selective inhibition of a serotonin receptor subtype (5-HT3). Ondansetron has marked activity against emesis associated with cisplatin and other highly emetogenic drugs. Compared with high doses of metoclopramide, the antiemetic "gold standard," it demonstrates equal or superior efficacy. Although ondansetron is moderately well absorbed after oral administration, only a parenteral formulation will initially be available. Ondansetron is eliminated almost entirely by hepatic metabolism; less than five percent of an intravenously administered dose is recovered intact in urine. The half-life of ondansetron is approximately 3.5 hours; slightly shorter in children and prolonged in the elderly. Neither clinical efficacy nor adverse effects have correlated with serum concentrations. Ondansetron is generally well tolerated. Clinically relevant adverse effects include headache, diarrhea or constipation, sedation, and transient minor elevations of liver function tests. It is not associated with extrapyramidal reactions. Ondansetron is indicated as prophylaxis for nausea and vomiting associated with emetogenic chemotherapy. Studies to further evaluate and define its use are ongoing.
Safety of ondansetron. [2013]The safety of ondansetron has been reviewed based on experience in its use as an anti-emetic treatment in about 1,400 patients receiving cancer treatment and further experience in about 650 volunteers and patients with other medical conditions. Evidence from animal pharmacology and toxicology had indicated that ondansetron had a wide therapeutic index, no interaction with commonly co-prescribed drugs, and no dependence liability. No end-organ toxicity had been seen. Clinical experience showed that ondansetron is well tolerated; the principal side effects being constipation and headache, which in the context of cancer treatment were not troublesome. Increases in liver function tests were observed, undoubtedly due in many instances to the underlying cancer or metastases and to chemotherapy, and the incidence was similar on ondansetron and metoclopramide. No extrapyramidal side effects were reported.
Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor. [2019]It has been previously shown that ondansetron, a 5-HT3 antagonist, can ameliorate vertigo in patients with acute brainstem disorders. A coincidental benefit was the improvement of cerebellar tremor in some patients with both vertigo and tremor. To further evaluate this effect, a placebo controlled, double blind, crossover study was conducted of a single dose of intravenous ondansetron in 20 patients with cerebellar tremor caused by multiple sclerosis, cerebellar degeneration, or drug toxicity. The principal outcome measures were the change in blind assessment of a writing task (spiral copying) and the timed completion of a nine hole peg test. Thirteen of 19 patients were deemed to have improved spiral copying after treatment with ondansetron when compared with baseline performance. One patient had a better response to the placebo compared with baseline performance (P = 0.00024). Patients completed the nine hole peg test in less time after ondansetron than after placebo (P = 0.08). Twelve patients thought that their tremor was functionally improved with the ondansetron treatment. None thought that the placebo gave improvement (P = 0.00098). The efficacy of orally administered ondansetron in tremor control is currently under study.
A protective effect of 5-HT3 antagonist against vestibular deficit? Metoclopramide versus ondansetron at the early stage of vestibular neuritis: a pilot study. [2014]Ondansetron is an antiemetic 5-HT3 receptor antagonist with proven efficacy in central balance disorder. A pilot study investigated impact on acute unilateral vestibular neuritis.
[Novel pharmacologic form of ondansetron (Zofran)--lingual tablets in the prevention of cytostatic chemotherapy-induced loss of appetite, nausea and vomiting]. [2015]Ondanserton (zofran), 16-32 mg/24 hr, lingual tablets, 2 days, was administered in 40 patients with advanced tumors who received combination chemotherapy (ABVD) (9 patients with Hodgkin's disease), CHOP (16--non-Hodgkin's lymphoma), gemzar + cisplatin (6--ovarian and 5--breast cancer), CAF, AC and taxol + carboplatin) (4). Distinct prophylactic antiemetic effect, delayed effect (94%) included, was reported in the CHOP group: full control--64% and partial control in gemzar + cisplatin treatment (27%). Loss of appetite was prevented in most patients receiving CHOP and gemzar + cisplatin. Untoward side-effects of ondansetron were not registered.
Ondansetron as an effective drug in prophylaxis of chemotherapy--induced emesis in children. [2013]The chemotherapy-induced emesis causes major complications, especially in children. Traditional prophylaxis of emesis shows moderate effectiveness alongside with pronounced adverse reactions. Ondansetron, an antagonist of 5-hydroxytryptamine (subtype 3) receptor is a new, very potent drug preventing vomiting and nausea induced by different factors (chemotherapy, radiotherapy, anaesthesia). We present results of an evaluation of the activity of ondansetron in 35 children receiving highly emetogenic chemotherapy during 129 days (102 with no cisplatin and 27 with cisplatin). On these days Zofran was administered as a single antiemetic agent. On 85 days the dosage was lower than recommended (the lowest 2 mg/m2/day). 16 out of the 35 patients received during 85 days traditional antiemetic treatment, and they constitute the control group. In chemotherapy without cisplatin complete and major responses were observed in 85.3% of the patients, in chemotherapy including cisplatin the respective response rate amounted to 71.4% while with, the traditional antiemetics the response rate was 38.8%. The dose reduction does not seem to have negatively affected the results, since they are comparable with those reported in the literature. Similar favourable effects were achieved in 8 children in which Zofran was used during the conditioning for bone marrow transplantation. This is of special significance in children conditioned with busulfan. This agent may be given only orally, and the effectiveness of the treatment depends directly on the dose of the administered drug. No adverse effects linked to ondansetron were found. The patients reaction was very positive, as ondansetron causes no sedation. Ondansetron seems, therefore, to be an effective and safe antiemetic.
Evaluation of ondansetron as a drug for premedication. [2013]The potency of Ondansetron (Zofran, Glaxo), a highly specific 5HT3 antagonist in preventing the very unfavorable complication during introducing anesthesia, i.e. a Bezold-Jarisch reflex-like reaction, was studied in a clinical trial. A total of 20 patients (12 males and 8 females aged 19-65 years) admitted for clinical surgical treatment participated in the trial. Zofran (8 mg in 500 ml Ringer solution) was injected intravenously one hour before intubation at a flow rate of 8 ml. min-1. Systolic and diastolic blood pressure, central venous pressure, breathing frequency and minute ventilation, pCO2 and pO2 in venous blood, electrocardiogram monitoring (ECG) and several common features such as spontaneous muscle activity, palpebral reflexes, skin and mucose surfaces were continuously observed. Visual, auscultatory and X-ray control of the lungs was effected. It was found that blockade of 5HT3 receptors prevented the appearance of Bezold-Jarisch reflex-like reaction. The drug could successfully be used in anesthesiological practice.