Ondansetron Use for Preventing Pruritus in Patients Undergoing Cesarean Section

Timing of Ondansetron Use for Maximum Efficacy in Preventing Pruritus in Patients Undergoing Cesarean Section Under Spinal Anesthesia with Preservative Free Morphine.

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.

Study Overview

• Status: Recruiting
• Conditions: Pruritus Caused by Drug
• Intervention / Treatment: Drug: Ondansetron 8mg

Detailed Description

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.

The primary aim of this study is to observe in a randomized double-blinded trial if the timing of prophylactic administration of intravenous ondansetron can reduce the incidence and severity of intrathecal morphine-induced pruritus in patients undergoing Cesarean section (CS). The secondary aim is to establish the effect of intravenous ondansetron given at different time intervals following CS for postoperative nausea and vomiting (PONV). The primary study hypothesis is that patients receiving prophylactic intravenous ondansetron (15-30 minutes prior to intrathecal morphine) will experience a lower incidence and severity of intrathecal morphine-induced pruritus than patients receiving ondansetron administered at the time of umbilical cord clamping. The secondary study hypothesis is that CS patients receiving intravenous ondansetron 15-30 minutes prior to intrathecal morphine will have less nausea and vomiting than patients receiving ondansetron administered at the time of umbilical cord clamping.

As the effect of prophylactic administration of ondansetron in reducing pruritus or Nausea/Vomiting in cesarean section (CS) cases has not been studied and thus, this prospective study may help guide future clinical management of side effects caused by intrathecal morphine administration.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Justin Hruska, MD; Phone Number: 402-432-0985; Email: justinhruska1@gmail.com
• Study Contact Backup: Name: George M McKelvey, PhD; Phone Number: 3135986036; Email: geomckelvey@dmc.org

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Detroit Medical Center- Hutzel Women's Hospital
      • Contact: George M McKelvey, PhD; Phone Number: 3135986036; Email: gmckelve@dmc.org
      • Contact: Justin Hruska, MD; Phone Number: 402-432-0985; Email: justinhruska1@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. American Society of Anesthesiologists (ASA) physical status 1-3
2. Adult parturient (18 -50 years of age) scheduled to undergo elective cesarean delivery under spinal anesthesia
3. Patients must be willing and cognitively able to give written informed study consent

Exclusion Criteria:

1. Patients with an ASA physiological assessment greater than grade 3
2. Allergies to local anesthetics, opioids, or ondansetron
3. Coagulopathies precluding provision of spinal anesthesia
4. Pre-eclampsia with severe features
5. Eclampsia
6. Pre-intrathecal pruritus
7. Psychiatric or language deficiencies affecting assessment of pain
8. Insufficient understanding of the pain scoring system
9. Patients who receive any other regional anesthesia techniques
10. Patients on higher than a 100mg of daily morphine equivalent
11. Cardiac issues that would preclude spinal anesthesia (Congestive heart failure, Mitral or Aortic valve pathology.
12. Confounding neural issues that would preclude spinal anesthesia.
13. Coadministration of drugs that would potentially interact with ondansetron. Including Apomorphine, Phenytoin, Carbamazepine, Rifampicin, Tramadol and Chemotherapy drugs.

14. Coadministration of drugs that would potentially prolong QTc interval. Including Antiarrhythmic, Antidepressants, Antipsychotics, and the following list of medications.

    a. Levofloxacin, Ciprofloxacin, Gatifloxacin, Moxifloxacin, Clarithromycin, Erythromycin, Ketoconazole, Itraconazole, Cisapride, Sumatriptan, Zolmitriptan, Arsenic, Dolasetron, Methadone

15. Coadministration of drugs that would potentially lead to the development of serotonin syndrome. Including the following:

    a. Selective serotonin reuptake inhibitors, Serotonin and norepinephrine reuptake inhibitors, antidepressants, carbamazepine , valproic acid, triptans, Chronic pain medications prior to procedure (Fentanyl, Hydrocodone, Meperidine, Oxycodone, tramadol),Lithium, dextromethorphan, Linezolid and Ritonavir

16. Patients having the following

    1. Patients known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any components of the formulation
    2. Concomitant use of apomorphine
    3. History of QTc interval prolongation (QTc >440) and Torsade de Pointes
    4. Serotonin syndrome
    5. Phenylketonuric patients
    6. Concurrent use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1. Pre-Intrathecal; 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.	Drug: Ondansetron 8mg; administration of an IV solution of 8mg ondansetron (4ml); Other Names: Placebo- 4ml of 0.9% IV saline
Active Comparator: Treatment Group 2 Cord clamping; 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.	Drug: Ondansetron 8mg; administration of an IV solution of 8mg ondansetron (4ml); Other Names: Placebo- 4ml of 0.9% IV saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pruritus parameters in Post anesthesia Care Unit (PACU)	Patient Assessment (patient questionnaire): Pruritus occurrence (Yes or no) and anatomical location of Pruritus of occurrence, Severity of Pruritus- Likert scale choices from (Not present, Mild, Moderate, Severe, Unbearable) severity	Assessment during 1st post-operative hour in PACU
Pruritus severity in Post anesthesia Care Unit (PACU)	Severity of Pruritus- Likert scale choices from (Not present, Mild, Moderate, Severe, Unbearable) severity	Assessment during 1st post-operative hour in PACU
Pruritus parameters PACU	Patient Assessment (patient questionnaire): Pruritus occurrence (Yes or no) and anatomical location of pruritus location	Assessment during 24 hours post-operative period
Pruritus severity PACU	Patient Assessment (patient questionnaire): Pruritus Severity: Likert scale: choice of (Not present, Mild, Moderate, Severe, Unbearable)	Assessment during 24 hours post-operative period
Nausea PACU	Patient Assessment questionnaire: Severity of Nausea- Likert scale: choice of (Not present, Mild, Moderate, Severe, Unbearable)	Assessment every 15 minutes for 1 hour
Rescue Pruritus Treatment medication	Patient Assessment questionnaire: If rescue Pruritus treatment was required (YES/NO) and if so specific medication type and dose amount of medication	Measured in the 24 hour period from initial study treatment (30 minute period before intrathecal morphine administration.
Nausea Post PACU	Patient Assessment questionnaire: Severity of Nausea- Likert scale: choice of (Not present, Mild, Moderate, Severe, Unbearable)	our period after patients left PACU from initial study treatment (30 minute period before intrathecal morphine administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Pain	Patient assessment questionnaire: Visual analog pain scale (VAS) measuring scores from 0 (no pain)-10 (worst pain) at rest	Taken while patient in PACU at 0 minutes, 15 minutes, 30 minutes, 45 minutes and 60 min. Post PACU patient assessment at at 8 hours, 16 hours, 24 hours post-operative period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral oxygen saturation- Mother	Clinical Measurement of patient Peripheral blood oxygen saturation (percentage %) via a pulse oximeter	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Peripheral oxygen saturation- Infant	Clinical Measurement of patient Peripheral blood oxygen saturation (percentage %) via a pulse oximeter	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Heart rate- Mother	Clinical Measurement of patient heart rate (beats per minute) via a pulse oximeter	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Heart rate- Infant	Clinical Measurement of patient heart rate (beats per minute) via a pulse oximeter	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Blood pressure Mother	Clinical Measurement of patient blood pressure (Diastolic/Systolic pressure mm/Hg) 0	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Blood pressure- Infant	Clinical Measurement of patient blood pressure (Diastolic/Systolic pressure mm/Hg) 0	At Delivery, then at 30 minutes, 60 minutes, 90 minutes, 2 hours, 8 hours,16 hours, 24 hours post-delivery
Electrocardiogram (ECG ) Mother	ECG parameters (ECG QT intervals) interpreted by a by a trained Cardiologist	Within 2 hours of birth.
ECG Infant	ECG parameters (ECG QT intervals) interpreted by a by a trained Cardiologist	Within 2 hours of birth.

Collaborators and Investigators

• Sponsor: Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Ondansetron; Cesarean Section; Intrathecal Morphine
• Additional Relevant MeSH Terms: Skin Manifestations; Skin Diseases; Pruritus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dermatologic Agents; Neurotransmitter Agents; Antipruritics; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Ondansetron
• Other Study ID Numbers: IRB-22-07-4803

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No