Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide

Phase 2

Not yet recruiting

• Conditions: Nausea and Vomiting; Nausea; Vomiting
• Interventions: Drug: Fosaprepitant; Drug: Metoclopramide

• Registration Number: NCT06740812
• Lead Sponsor: Montefiore Medical Center

Brief Summary

The study team proposes a double-blind, comparative effectiveness, randomized controlled trial (RCT) to address the following goal: to determine the relative efficacy and adverse event profile of fosaprepitant compared to the standard of care antiemetic metoclopramide. 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 emergency departments (EDs). Intravenous fosaprepitant is converted to the active metabolite aprepitant on the order of minutes and is significantly cheaper to procure at this time.

Detailed 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 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.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-14
• Study First Submitted QC: 2024-12-14
• Last Update Submitted: 2024-12-14
• Study First Posted: 2024-12-18
• Last Update Posted: 2024-12-18
• Study Start: 2025-06
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

• Adults at least 18 years old
• Present to ED for treatment of 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 presenting to ED for evaluation and management
• Bradycardia (< 60 bpm heart rate)
• Prolonged QTc (greater than 490ms)
• Not conversant in English or Spanish
• Altered mental status
• Dementia
• Lack of phone for follow-up communication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Investigational Intervention	Fosaprepitant	Fosaprepitant
Standard-of-Care Intervention	Metoclopramide	Metoclopramide

Primary Outcome Measures

Name	Time	Method
Sustained Nausea and Vomiting (NV) Relief	2 hours (assessed at the 2-hour mark after administration of the intervention)	The primary efficacy outcome for this study will be sustained relief from NV at 2 hours following medication administration. Sustained relief from NV will be determined by the intensity of nausea reported by patients following administration of antiemetic. Intensity of nausea will be reported as either "None", "Mild", "Moderate" or "Severe." The number/percentage of patients reporting each degree of nausea intensity at 2 hours will be summarized by study arm.; Sustained relief of NV 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 2 hours of medication administration without the use of any rescue medication. Patients who do not report an initial nausea intensity of either "Severe" or "Moderate" will not be assessed as they are not eligible for the study.
Development of New Symptom	2 hours (assessed at the 2-hour mark after administration of the intervention)	The primary tolerability outcome for this study will be the onset of any new symptoms within 2 hours after medication administration. Onset of symptoms will be assessed by asking patients if they developed any new symptoms after administration of the investigational medication. Symptoms will be elicited using an open-ended format. Patients who confirmed that they had experienced new symptoms will be asked to grade the severity of the new symptom(s) using the descriptors "Mild", "Moderate", or "Severe". The frequency and intensity of new symptoms will be summarized by study arm using basic descriptive statistics.

Secondary Outcome Measures

Name	Time	Method
Sustained NV Relief	24 hours following medication administration	Sustained relief from NV will be determined by the intensity of nausea reported by patients following administration of antiemetic. Intensity of nausea will be reported as either "None", "Mild", "Moderate" or "Severe." The number/percentage of patients reporting each degree of nausea intensity at 24 hours will be summarized by study arm.; Sustained relief of NV 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 2 hours of medication administration AND maintained at "Mild" or "None" level for the entire 24-hour period following medication administration, without the use of rescue medication.
NV Relief	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)	Relief of NV over time will be determined by the intensity of nausea reported by patients following administration of antiemetic. Intensity of nausea will be reported as either "None", "Mild", "Moderate" or "Severe" and assessed every 15 minutes during the first 2 hours, then every hour after that up to 24 hours. The number/percentage of patients reporting each degree of nausea intensity at each timepoint will be summarized by study arm using basic descriptive statistics. Sustained relief of NV requires a patient to present with an initial nausea intensity of either "Severe" or "Moderate" and assessments will only be made in patients who did not need rescue medication.
NV Freedom	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)	Freedom from NV over time will be determined by the intensity of nausea reported by patients following administration of antiemetic. Intensity of nausea will initially be reported as either "None", "Mild", "Moderate" or "Severe" and assessed every 15 minutes during the first 2 hours, then every hour after that up to 24 hours. The number/percentage of patients reporting a nausea intensity of "None" will be summarized by study arm using basic descriptive statistics. Sustained freedom from NV requires a patient to present with an initial nausea intensity of either "Severe" or "Moderate" and assessments will only be made in patients who did not receive rescue medication.
Sustained NV Freedom	24 hours following medication administration	Sustained NV Freedom will be determined by the intensity of nausea reported by patients following administration of antiemetic. Intensity of nausea will initially be reported as either "None", "Mild", "Moderate" or "Severe." The number/percentage of patients reporting a nausea intensity of "None" will be summarized by study arm using basic descriptive statistics.; Sustained NV Freedom requires a patient to present with a nausea intensity of either "Severe" or "Moderate," which is then reduced by treatment to "None" within 2 hours of medication administration AND maintained at the same ("None") level for the entire 24-hour period following medication administration, without the use of rescue medication.
Medication Preference	24 hours	Patient preference for receiving the same antiemetic medication as was administered during the study in the event of a subsequent episode of NV will be assessed during a follow-up phone call. Patients will be asked, "The next time you come to the ED for treatment of nausea and vomiting, do you want to receive the same medication again?" Patients will select from the following responses ("Yes," "No," or "Not sure"). Patient responses will be summarized and reported by study arm using basic descriptive statistics.
Duration of ED Stay	Initial presentation to disposition, approximately 4 hours	Mean duration of ED stay, defined as the interval of time from initial presentation in ED to disposition, will be determined. ED durations will be summarized and reported by study arm using basic descriptive statistics. Prolonged LOS is generally associated with increased treatment complications and less favorable outcomes.

Trial Locations

Locations (1)

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States