Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide (BARF RCT)

Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide: A Randomized Control Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nausea; Vomiting; Nausea and Vomiting
• Intervention / Treatment: Drug: Fosaprepitant for Injection; Drug: Metoclopramide Injection

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 Type: Interventional
• Enrollment (Estimated): 212
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mustfa K Manzur, MD MPH MS; Phone Number: 718-920-6626; Email: mmanzur@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
      • Contact: Campus IRB; Phone Number: 718-430-2237; Email: clinicaltrials.gov@einsteinmed.edu
      • Principal Investigator: Mustfa K Manzur, MD MPH MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Intervention; Fosaprepitant	Drug: Fosaprepitant for Injection; Fosaprepitant 150mg IV administered over 15 minutes
Active Comparator: Standard-of-Care Intervention; Metoclopramide	Drug: Metoclopramide Injection; Metoclopramide 10mg IV administered over 15 minutes; Other Names: Reglan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Nausea and Vomiting (NV) Relief	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.	2 hours (assessed at the 2-hour mark after administration of the intervention)
Development of New Symptom	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.	2 hours (assessed at the 2-hour mark after administration of the intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained NV Relief	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.	24 hours following medication administration
NV Relief	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.	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)
NV Freedom	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.	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)
Sustained NV Freedom	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.	24 hours following medication administration
Medication Preference	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.	24 hours
Duration of ED Stay	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.	Initial presentation to disposition, approximately 4 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Nausea	Severity of nausea will be evaluated based on responses to a visual analogue scale ranging from 0 to 100 (0 = no nausea, 100 = worst nausea possible). Mean scores will be summarized and reported by study arm. Higher scores are associated with increased severity of nausea.	24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
QTc Interval (QT interval corrected for heart rate)	Mean QTc durations, as calculated from electrocardiogram (ECG) readings administered prior to receiving intervention, and at disposition, will be determined. Mean QTc durations will be summarized by study arm. 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
Need for rescue antiemetic medication	The need for rescue antiemetic medication during the study will be assessed using a binary outcome (i.e., "Yes: or "No") to summarize whether additional dosing of antiemetic medication to treat nausea was needed. Results will be summarized by study arm using basic descriptive statistics.	2 hours (assessed at the 2-hour mark after administration of the intervention)
Vomiting Episodes	The mean number of vomiting episodes per patient over the past 24 hours will be assessed and summarized by study arm.	Up to 24 hours
Hospitalization	The percentage of patients who required hospitalization within 24 hours due to NV symptoms will be determined and summarized by study arm. Hospitalizations are associated with increased complications and less favorable outcomes.	Up to 24 hours
Need for Fluid Treatment	The percentage of patients treated with intravenous (IV) fluids will be determined and summarized by study arm. The need for IV fluids is associated with increased supportive care, increased hospital LOS and less favorable outcomes.	4 hours
Mean Fluid Volume	For patients requiring IV fluids, the mean per patient volume of IV fluids administered will be summarized and reported by study arm. The need for, and increased volumes of, IV fluids is associated with increased supportive care, increased hospital LOS and less favorable outcomes.	4 hours
Revisit Rate to Emergency Department	For purposes of this study, revisit rate will be defined as the number/percentage of participants requiring a revisit to the ED for additional evaluation and management of NV. Results will be summarized by study arm using basic descriptive statistics. More frequent revisit rates are associated with increased complications and less favorable outcomes.	24 hours

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Benjamin Friedman, MD, Montefiore Medical Center

Publications and helpful links

General Publications

• Furyk JS, Meek RA, Egerton-Warburton D. Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. Cochrane Database Syst Rev. 2015 Sep 28;2015(9):CD010106. doi: 10.1002/14651858.CD010106.pub2.
• Braude D, Soliz T, Crandall C, Hendey G, Andrews J, Weichenthal L. Antiemetics in the ED: a randomized controlled trial comparing 3 common agents. Am J Emerg Med. 2006 Mar;24(2):177-82. doi: 10.1016/j.ajem.2005.08.017.
• Aapro M, Carides A, Rapoport BL, Schmoll HJ, Zhang L, Warr D. Aprepitant and fosaprepitant: a 10-year review of efficacy and safety. Oncologist. 2015 Apr;20(4):450-8. doi: 10.1634/theoncologist.2014-0229. Epub 2015 Mar 20.
• Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Available from http://www.ncbi.nlm.nih.gov/books/NBK52651/
• Mechanisms and Control of Emesis: A Satellite Symposium of the European Neuroscience Association: Proceedings of an International Meeting Held in Marseille (France), 4-7 September 1992. John Libbey Eurotext
• Singh P, Yoon SS, Kuo B. Nausea: a review of pathophysiology and therapeutics. Therap Adv Gastroenterol. 2016 Jan;9(1):98-112. doi: 10.1177/1756283X15618131.
• Pourmand A, Mazer-Amirshahi M, Chistov S, Sabha Y, Vukomanovic D, Almulhim M. Emergency department approach to QTc prolongation. Am J Emerg Med. 2017 Dec;35(12):1928-1933. doi: 10.1016/j.ajem.2017.08.044. Epub 2017 Aug 24.
• Franklin BJ, Vakili S, Huckman RS, Hosein S, Falk N, Cheng K, Murray M, Harris S, Morris CA, Goralnick E. The Inpatient Discharge Lounge as a Potential Mechanism to Mitigate Emergency Department Boarding and Crowding. Ann Emerg Med. 2020 Jun;75(6):704-714. doi: 10.1016/j.annemergmed.2019.12.002. Epub 2020 Jan 23.
• Langford P, Chrisp P. Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting. Core Evid. 2010 Oct 21;5:77-90. doi: 10.2147/ce.s6012.
• Yang Y, Yang N, Wu L, Ouyang Q, Fang J, Li J, Liao W, Cai K, Huang J, Li J, Zhang Y, Wang X, Zhang H, Xu N, Zhao Q, Hu X, Li W, Zhong W, Zhong D, Cheng G, Ye S, Zhong M, Wang D, Liu H, Zheng J, Liu X, Xu H, Zhang L. Safety and efficacy of aprepitant as mono and combination therapy for the prevention of emetogenic chemotherapy-induced nausea and vomiting: post-marketing surveillance in China. Chin Clin Oncol. 2020 Oct;9(5):68. doi: 10.21037/cco-20-160.
• Cham S, Basire M, Kelly AM. Intermediate dose metoclopramide is not more effective than standard dose metoclopramide for patients who present to the emergency department with nausea and vomiting: a pilot study. Emerg Med Australas. 2004 Jun;16(3):208-11. doi: 10.1111/j.1742-6723.2004.00588.x.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 14, 2024
• First Submitted That Met QC Criteria: December 14, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Adults; Physiological Effects of Drugs; Peripheral Nervous System Agents; Randomized Control Trial; Autonomic Agents; Neurotransmitter Agents; Metoclopramide; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Aprepitant; Gastrointestinal Agents; Fosaprepitant; Antipruritics; Signs and Symptoms, Digestive; Antiemetics; Neurokinin-1 Receptor Antagonists; Dopamine Receptor Antagonist
• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Signs and Symptoms, Digestive; Nausea; Vomiting; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydroxy Acids; Hydrocarbons, Aromatic; Amides; Phenols; Benzene Derivatives; Acids, Carbocyclic; para-Aminobenzoates; Aminobenzoates; Benzoates; Hydroxybenzoates; Phenyl Ethers; Benzamides; Chlorobenzoates; Hydroxybenzoate Ethers; Metoclopramide; Injections; fosaprepitant
• Other Study ID Numbers: 2024-16422

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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