Antiemetic Fosaprepitant To Remedy Nausea and Vomiting

Nausea Clinical Trial

— AFTR NV RCT  

Official title:

Antiemetic Fosaprepitant To Remedy Nausea and Vomiting

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06382012
• Other study ID #: 2024-15703
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: June 2024
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Montefiore Medical Center
• Contact: Mustfa K Manzur, MD MPH MS
• Phone: 718-920-6626
• Email: mmanzur[@]montefiore.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study team proposes a randomized, double-blind, RCT to address the following goal: to determine the relative efficacy and adverse event profile of fosaprepitant compared to the standard of care antiemetic ondansetron. Fosaprepitant and its active metabolite aprepitant are a relatively new class of antiemetic that exclusively acts in the central nervous system by blocking neurokinin (NK-1) which is a key signaling molecule in the centrally mediated aspects of the vomiting reflex. Currently, fosaprepitant and aprepitant both have only two United Stated Food and Drug Administration (USFDA) approved indications for nausea and vomiting: chemotherapy-induced and postoperative. Neurokinin inhibitors are highly effective and generally well-tolerated. Therefore, this class of medication may be a more appropriate medication for the millions of patients with nausea and vomiting that seek care in EDs. Intravenous fosaprepitant is converted to the active metabolite aprepitant on the order of minutes and is significantly cheaper to procure at this time. The outcome for the efficacy analysis will be no need for additional medication to treat nausea and vomiting within 2 hours of investigational medication administration. The primary outcome for the tolerability analysis will be the development of any new symptom within 2 hours of medication administration.

Description:

Nausea and vomiting (NV) are common and interrelated conditions. Approximately 50% of adults experience nausea in a given year while 30% of adults experience vomiting over the same period. Of this population of symptomatic individuals with NV, 25% of patients seek care in any healthcare delivery setting. Health Care Utilization Project (HCUP) data indicates that nearly 9.0 million patients seek care for NV in emergency departments (EDs) each year in the United States.

Antiemetics are used to treat NV. Antiemetics currently utilized in the emergency department setting for NV do not always work on the first dose and have a plethora of side effects because of their peripheral mechanism of action outside of the vomiting reflex pathway in the central nervous system. These medications include ondansetron, promethazine, metoclopramide, olanzapine, haloperidol. Chief among these side effects is alteration of an aspect cardiac electrical signaling called the QT segment which represents the duration of ventricular contraction and relaxation. The QT segment is prolonged with commonly used antiemetics which can often be a prelude to cardiac dysrhythmias that are associated with mortality. As a result, patients with NV often have long length-of-stay (LOS) involving supportive care with intravenous fluids or empiric treatment with medications that can potentiate development of cardiac dysrhythmias. This is a problem in busy emergency departments (EDs) struggling to accelerate patient throughput in order to appropriately keep up with patient volume in an under-supplied hospital bed environment nationally.

Fosaprepitant and its active metabolite aprepitant are a relatively new class of antiemetic that exclusively acts in the central nervous system by blocking neurokinin (NK-1) which is a key signaling molecule in the centrally mediated aspects of the vomiting reflex. Currently, fosaprepitant and aprepitant both have only two United Stated Food and Drug Administration (USFDA) approved indications for nausea and vomiting: chemotherapy-induced and postoperative. Neurokinin inhibitors are highly effective and generally well-tolerated. Therefore, this class of medication may be a more appropriate medication for the millions of patients with nausea and vomiting that seek care in EDs. Intravenous fosaprepitant is converted to the active metabolite aprepitant on the order of minutes and is significantly cheaper to procure at this time.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults at least 18 years old

• Present for nausea and/or vomiting as defined by the International Classification of Diseases (ICD-10) or identified by treating clinician

Exclusion Criteria:

• Pregnancy, desiring pregnancy, or lactating

• Antiemetic use or intravenous fluids prior to screening

• Bradycardia (less than 60 bpm heart rate)

• Prolonged QTc (greater than 460ms)

• Not conversant in English or Spanish

• Altered mental status

• Dementia

• Lack of phone for follow-up communication

Related Conditions & MeSH terms

• Nausea
• Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Fosaprepitant 150 mg
Fosaprepitant 150mg IV administered over 15 minutes
• Ondansetron 4 mg
Ondansetron 4mg IV administered over 15 minutes

Locations

Country	Name	City	State
United States	Montefiore Medical Center (Montefiore and Weiler EDs)	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
Montefiore Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Relief from NV	Sustained relief from nausea and vomiting will be determined by the intensity of nausea reported by participants following administration of antiemetic. Intensity of nausea will be reported as either None, Mild, Moderate, or Severe. The number/percentage of participants reporting each degree of nausea intensity will be summarized; Sustained relief of nausea and vomiting requires a patient to present with a nausea intensity of either "severe" or "moderate," which is then reduced by treatment to at least "mild" or "none," within two hours of medication administration, and then maintained at "mild" or "none" level for the entire 24-hour period following medication administration without the use of rescue medication.	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
Secondary	Severity of Nausea	Mean severity of nausea scores will be evaluated and summarized based on a visual analogue scale from 0 to 100 (0 = no nausea, 100 = worst nausea possible)	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
Secondary	Need for rescue antiemetic medication	Binary outcome for needing or not needing additional dosing of antiemetic medication to treat nausea will be determined	2 hours (assessed at the 2 hour mark after administration of the intervention)
Secondary	Medication Preference	Participant preference for receiving the same antiemetic medication as administered for a subsequent episode of nausea and vomiting will be determined. Binary (Yes/No) responses will be summarized	24 hours
Secondary	Functional disability	Patient reported functional disability will be assessed. Functional disability will be categorized as either severe, moderate, mild, or not impaired, and summarized	24 hours (assessed prior to receiving intervention, at 2 hour point after receiving intervention, and 24 hours after intervention)
Secondary	Vomiting	The mean number of vomiting episodes per patient will be assessed and summarized	24 hours
Secondary	Hospitalization	The percentage of patients who require hospitalization within 24 hours due to NV symptoms will be determined	24 hours
Secondary	Fluid Treatment	The percentage of patients treated with IV fluids will be determined	4 hours
Secondary	Mean Fluid Volume	The mean per patient volume of IV fluids administered will be summarized	4 hours
Secondary	Length of Stay	Mean length of stay, defined as the interval of time from initial presentation to disposition, will be determined	Initial presentation to disposition, approximately 4 hours
Secondary	QTc Interval (QT interval corrected for heart rate)	Mean QTc durations, as calculated from ECG readings administered prior to receiving intervention and at disposition, will be determined. Prolonged QT interval is commonly associated with antiemetics and can often be a prelude to cardiac dysrhythmias associated with mortality	Prior to Intervention and at disposition, approximately 2 hours
Secondary	Revisit Rate	Revisit rate will be assessed as the number/percentage of participants requiring a revisit to the Emergency department for NV	24 hours