Ondansetron for Fainting Prevention

(POST 11 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Blood pressure medications

Disqualifiers: Heart block, Hypertension, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

70 Participants Needed

Trial Summary

What is the purpose of this trial?

About 20% of adults faint recurrently. These patients are often highly symptomatic, have problems with employment and driving, can be injured, and have poor quality of life. There are few therapies that have withstood the test of randomized clinical trials. the investigators will conduct a prospective, randomized, parallel, double-blind, proof-of-concept study that tests the hypothesis that serotonin 5HT3 receptor inhibition with ondansetron prevents tilt-induced vasovagal syncope (VVS) and pre-syncope in patients with clinical VVS. A total of 70 patients with quantitative clinical diagnostic criteria for VVS and at least 1 syncopal spell in the preceding year will be randomized in a double-blind acute phase 2 study to ondansetron 8 mg PO BID x 2 doses or matching placebo. The endpoint will be presyncope or syncope associated with diagnostic hemodynamic changes. These data should provide useful preliminary data as a foundation on which to conduct a subsequent randomized clinical trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on medications that affect blood pressure.

What evidence supports the effectiveness of the drug ondansetron for preventing fainting?

Ondansetron, a drug known for preventing nausea and vomiting, has shown effectiveness in treating balance disorders and reducing symptoms like vertigo, which are related to fainting. This suggests it might help in preventing fainting by stabilizing balance. ^{1 2 3 4 5}

Is ondansetron safe for humans?

Ondansetron is generally safe for humans, with common side effects being headache and constipation. It has been well-tolerated in various studies, including those involving cancer patients, with no major toxicity or serious side effects reported. ^{1 4 6 7 8}

How does the drug Ondansetron differ from other treatments for fainting prevention?

Ondansetron is unique for fainting prevention because it is primarily known as a 5-HT3 receptor blocker used to prevent nausea and vomiting, which is different from typical treatments for fainting that may not target this specific receptor. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for adults who have fainted at least once in the past year and score ≥-2 on a specific fainting symptom scale. Participants must be over 18, able to consent, and not have other causes of fainting like heart issues or low blood pressure. Pregnant women, those with glaucoma, or people on certain medications can't join.

Inclusion Criteria

I am 18 years or older and can give informed consent.

You have a score of less than -2 on the Calgary Syncope Symptom Score.

I have fainted at least once in the past year.

Exclusion Criteria

I am taking medication that affects my blood pressure.

I have glaucoma.

Other factors which, in the investigator's opinion, would prevent the subject from completing the protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of Ondansetron 8 mg PO or matching placebo before undergoing a tilt table test

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cardiac output, anxiety, depression, and quality of life

12 months

Treatment Details

Interventions

• Ondansetron
• Placebo

Trial Overview The study tests if Ondansetron (a drug that blocks certain serotonin receptors) can prevent fainting when standing up due to vasovagal syncope. It's a double-blind test where half the patients get Ondansetron and half get a placebo without knowing which one they're taking.

Participant Groups

Group I: Ondansetron Active Control 1 Intervention

2 doses of Ondansetron 8mg PO (evening before and morning of study)

Group II: Placebo Active Control 1 Intervention

2 doses of matching placebo 8 mg PO (evening before and morning of study)

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?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

In a study of 90 surgical patients, ondansetron 4 mg administered before anesthesia significantly reduced the incidence of postoperative nausea and vomiting (PONV) compared to a placebo, with nausea occurring in only 13% of patients receiving ondansetron before induction versus 67% in the control group.

The study found no significant adverse effects related to ondansetron administration, confirming its safety and efficacy as a prophylactic treatment for PONV in surgical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of postoperative nausea and vomiting with ondansetron: a prospective, randomized, double-blind study in 90 patients]. Polati, E., Finco, G., Bartoloni, A., et al.[2013]

In a study involving 2,199 patients undergoing outpatient surgery, a repeat dose of ondansetron 4 mg i.v. after initial prophylaxis did not significantly improve control of postoperative nausea and vomiting (PONV) compared to placebo.

The additional ondansetron dose did not increase adverse effects, indicating it is safe to administer, but it was ineffective in providing further relief for patients who still experienced PONV after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. Kovac, AL., O'Connor, TA., Pearman, MH., et al.[2022]

Ondansetron, a 5-HT3 receptor antagonist, is well-established for treating nausea and vomiting from chemotherapy and surgery, but it also shows potential benefits for various conditions like drug overdosage, gastrointestinal motility disorders, and certain neurological issues, based on preliminary data.

The drug is generally well tolerated with a lower risk of sedation and does not worsen Parkinson's disease symptoms, making it a promising alternative for patients with refractory conditions or those who cannot tolerate current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Wilde, MI., Markham, A.[2018]

In a study of 50 women undergoing surgery, ondansetron significantly reduced the number of vomiting episodes and subjective nausea scores compared to a placebo, demonstrating its efficacy in preventing postoperative nausea and vomiting.

The safety profile of ondansetron was comparable to that of the placebo, indicating that it is a safe option for managing nausea and vomiting after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron is effective in decreasing postoperative nausea and vomiting. Dershwitz, M., Rosow, CE., Di Biase, PM., 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 270 adults with nausea and vomiting in the emergency department, both ondansetron and metoclopramide showed similar effectiveness in reducing nausea severity compared to placebo, with mean decreases in nausea scores of 27 mm and 28 mm respectively.

While both ondansetron and metoclopramide had trends indicating better outcomes in patient satisfaction and lower need for rescue medication compared to placebo, these differences were not statistically significant, suggesting that all treatments were similarly effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Egerton-Warburton, D., Meek, R., Mee, MJ., et al.[2014]

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]

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 two 12-month trials involving 1130 patients with intermittent and mild persistent asthma, as-needed formoterol (4.5 microg) was found to be as effective as terbutaline (0.5 mg) in improving morning peak expiratory flow (PEF) and managing symptoms.

Formoterol demonstrated a better safety profile with fewer systemic effects compared to terbutaline when administered in higher doses, indicating it is a safe and effective option for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formoterol used as needed in patients with intermittent or mild persistent asthma. Chuchalin, A., Kasl, M., Bengtsson, T., et al.[2015]

In a study involving 20 children with asthma, inhaling formoterol (4.5 microg) was found to be at least as safe as terbutaline (500 microg), with fewer systemic side effects reported, particularly tremors.

Formoterol demonstrated similar systemic activity to a lower dose of terbutaline (250 microg), indicating that it may be a more tolerable option for managing asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline. Kaae, R., Agertoft, L., Pedersen, S., et al.[2018]

In a study of 692 COPD patients, formoterol (9 and 18 microg b.i.d.) significantly reduced symptoms like breathlessness and chest tightness, and increased the number of symptom-free days, demonstrating its efficacy in managing COPD symptoms.

Formoterol also improved lung function across all doses tested (4.5, 9, and 18 microg b.i.d.) without any unexpected adverse events, indicating it is a safe treatment option for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial. Aalbers, R., Ayres, J., Backer, V., et al.[2019]

A large international clinical trial is underway to compare the efficacy of tiotropium and salmeterol in preventing COPD exacerbations, involving at least 6800 patients with a history of smoking and previous exacerbations.

The primary focus of the trial is the time to the first exacerbation, with careful design to address challenges in measuring exacerbations, ensuring reliable and relevant results for COPD treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations. Beeh, KM., Hederer, B., Glaab, T., et al.[2021]

In a study involving 47 patients with COPD, ipratropium bromide significantly improved lung function compared to placebo, demonstrating effective bronchodilation.

However, adding oral ondansetron, either as a single or repeated dose, did not enhance the bronchodilation effects of ipratropium bromide, indicating that ondansetron does not modify the therapeutic action of ipratropium in COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD. Pauwels, R., Joos, GF., Fogarty, C., et al.[2013]

References

1. Italy pubmed.ncbi.nlm.nih.gov

[Prevention of postoperative nausea and vomiting with ondansetron: a prospective, randomized, double-blind study in 90 patients]. [2013]

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

Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. [2018]

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

Ondansetron is effective in decreasing postoperative nausea and vomiting. [2019]

5. 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]

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

Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. [2014]

7. England pubmed.ncbi.nlm.nih.gov

Safety of ondansetron. [2013]

8. England pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Formoterol used as needed in patients with intermittent or mild persistent asthma. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial. [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD. [2013]