Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide

NCT06740812 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2024-16422
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

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.

Conditions

Nausea and Vomiting; Nausea; Vomiting

Keywords

Signs and Symptoms, Digestive; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipruritics; Dermatologic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurokinin-1 Receptor Antagonists; Fosaprepitant; Aprepitant; Dopamine Receptor Antagonist; Randomized Control Trial; Metoclopramide; Adults

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Sustained NV Relief

  24 hours following medication administration

• NV Relief

  24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)

• NV Freedom

  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

  24 hours following medication administration

• Medication Preference

  24 hours

Other Outcomes (8)

• 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)

  Prior to Intervention and at disposition, approximately 2 hours

• Need for rescue antiemetic medication

  2 hours (assessed at the 2-hour mark after administration of the intervention)

Study Arms (2)

Investigational Intervention

EXPERIMENTAL

Fosaprepitant

Drug: Fosaprepitant for Injection

Standard-of-Care Intervention

ACTIVE COMPARATOR

Metoclopramide

Drug: Metoclopramide Injection

Interventions

Fosaprepitant for Injection DRUG

Fosaprepitant 150mg IV administered over 15 minutes

Investigational Intervention

Metoclopramide Injection DRUG

Metoclopramide 10mg IV administered over 15 minutes

Also known as: Reglan

Standard-of-Care Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (11)

• 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

  BACKGROUND

• 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.

  PMID: 26770271 BACKGROUND

• 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/

  PMID: 21413206 BACKGROUND

• 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.

  PMID: 28855066 BACKGROUND

• 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.

  PMID: 31983501 BACKGROUND

• 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.

  PMID: 25795636 BACKGROUND

• 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.

  PMID: 21042544 BACKGROUND

• 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.

  PMID: 26411330 BACKGROUND

• 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.

  PMID: 33161724 BACKGROUND

• 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.

  PMID: 16490647 BACKGROUND

• 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.

  PMID: 15228463 BACKGROUND

MeSH Terms

Conditions

Nausea; Vomiting; Signs and Symptoms, Digestive

Interventions

fosaprepitant; Injections; Metoclopramide

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Study Officials

• Benjamin Friedman, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mustfa K Manzur, MD MPH MS

CONTACT

718-920-6626; mmanzur@montefiore.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2024
• First Posted: December 18, 2024
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

US (1)