Ondansetron for Drug-Induced Itching

Overseen By George M McKelvey, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Wayne State University

Must not be taking: Antidepressants, Antipsychotics, Chemotherapy, others

Disqualifiers: Pre-eclampsia, Eclampsia, Cardiac issues, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate perioperative period

66 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial, especially if they interact with ondansetron or affect heart rhythm. These include some antidepressants, pain medications, and antibiotics. It's best to discuss your current medications with the trial team to see if any changes are needed.

What evidence supports the effectiveness of the drug ondansetron for treating drug-induced itching?

Ondansetron has shown effectiveness in reducing itching in conditions like cholestatic pruritus, where it significantly reduced itch intensity in patients. However, its effectiveness in treating other types of drug-induced itching, such as those caused by opioids or in hemodialysis patients, has been less clear or not significant. ^{1 2 3 4 5}

Is ondansetron safe for humans?

Ondansetron, also known as Zofran, is generally considered safe for humans. Common side effects include headache and constipation, and in rare cases, it may cause a hypersensitivity reaction like itching and rashes. ^{6 7 8 9 10}

How does the drug ondansetron differ from other treatments for drug-induced itching?

Ondansetron is unique because it is primarily used to prevent nausea and vomiting, often related to chemotherapy or surgery, by blocking serotonin receptors in the brain. Its use for drug-induced itching is novel, as there are no standard treatments specifically for this condition, making ondansetron a potentially new option for patients experiencing this type of itching. ^{11 12 13 14 15}

What is the purpose of this trial?

Opioids are often added with a local anesthetic to enhance the duration and quality of spinal anesthesia for cesarean delivery patients. However, spinal opioids are associated with a wide variety of side effects such as nausea, vomiting, (N/V) and pruritus (itching). The occurrence of pruritus can vary between 30% and 100% making pruritus the most common side-effect of intrathecal opioids and this rate is even higher in pregnant patients. Pruritus may require treatment which can be ineffective or sometimes reverse the analgesic effect of the opioids. Ondansetron is a safe and very commonly used Serotonin receptor antagonist treatment for local anesthetic opioid-induced pruritus used in pregnancy. The effect of different administration times of ondansetron in reducing pruritus or N/V in cesarean section (CS) cases has not been extensively studied and thus, this prospective study can help guide future clinical management of side effects caused by spinal intrathecal morphine administration.

Eligibility Criteria

This trial is for pregnant women undergoing cesarean section who experience itching due to spinal opioids used in anesthesia. Participants should not have any conditions that would make using Ondansetron unsafe.

Inclusion Criteria

My health is good to moderately impaired.

I am willing and able to consent to participate in the study.

I am between 18 and 50 years old and scheduled for a C-section with spinal anesthesia.

Exclusion Criteria

I have been diagnosed with serotonin syndrome.

I am not taking medications that increase serotonin levels.

Insufficient understanding of the pain scoring system

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous ondansetron at different time intervals to assess its efficacy in reducing pruritus and nausea during cesarean section

Immediate perioperative period

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for pruritus, nausea, and other vital signs during the post-operative period

24 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Ondansetron

Trial Overview The study tests if giving Ondansetron (8mg) at different times can reduce itching or nausea and vomiting caused by opioids added to local anesthetics during cesarean sections. It's a prospective study, meaning it observes outcomes over time.

Participant Groups

Group I: Treatment Group 1. Pre-Intrathecal Experimental Treatment 1 Intervention

Patients will receive an IV solution of 8mg ondansetron (4ml) within 30 minutes of the standard-of-care anesthetic treatment (intrathecal morphine administration) followed by a placebo treatment of an IV solution of 4ml 0.9% saline administered at the time of umbilical cord clamping.

Group II: Treatment Group 2 Cord clamping Active Control 1 Intervention

Patients will receive a placebo treatment of an IV solution of 4ml 0.9% saline administered within 30 minutes of the standard-of-care anesthetic treatment (intrathecal morphine administration) followed by an IV solution of 8mg ondansetron (4ml) administered at the time of umbilical cord clamping.

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

Findings from Research

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]

Ondansetron, administered intravenously at 4 mg once daily for 3-5 days, effectively controlled nausea in 59% and emesis in 68% of patients receiving non-platinum anticancer drugs, demonstrating its efficacy as an anti-emetic.

The safety profile of Ondansetron was strong, with 98% of cases showing no safety issues, and only minor side effects like headache and constipation reported in a few instances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs]. Nukariya, N., Niitani, H., Taguchi, T., et al.[2013]

Intranasal zolmitriptan provides rapid relief for migraine sufferers, with plasma drug levels detectable within 2 minutes and central nervous system effects occurring just 3 minutes later, showing significant efficacy compared to placebo within 10 to 15 minutes after administration.

This formulation is particularly beneficial for patients who prefer not to self-inject or who experience gastrointestinal issues, highlighting its potential as a preferred option for acute migraine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy. Goadsby, PJ., Yates, R.[2014]

References

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

Prophylactic ondansetron does not reduce the incidence of itching induced by intrathecal sufentanil. [2015]

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

A randomized, placebo-controlled, double-blind trial of ondansetron in renal itch. [2019]

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

Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. [2022]

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

Ondansetron therapy for uremic pruritus in hemodialysis patients. [2019]

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

Management of opioid-induced pruritus: a role for 5-HT3 antagonists? [2022]

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

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

7. Japan pubmed.ncbi.nlm.nih.gov

[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs]. [2013]

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

Practical points in the use of ondansetron. [2013]

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

Hypersensitivity reaction to intravenous ondansetron: A case report. [2022]

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

A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. [2019]

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

Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy. [2014]

12. Spain pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of zolmitriptan in migraine]. [2014]

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

The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective. [2020]

14. India pubmed.ncbi.nlm.nih.gov

The therapeutic profile of zolmitriptan in clinical practice. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Effect of sumatriptan, a new selective 5HT1-like agonist, on liquid gastric emptying in man. [2022]