Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide

Official title

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

Overview

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.

Interventions

• Drug Fosaprepitant for Injection
  Fosaprepitant 150mg IV administered over 15 minutes
• Drug Metoclopramide Injection
  Metoclopramide 10mg IV administered over 15 minutes

Primary outcome measures

• Sustained Nausea and Vomiting (NV) Relief [Time frame: 2 hours (assessed at the 2-hour mark after administration of the intervention)]
• Development of New Symptom [Time frame: 2 hours (assessed at the 2-hour mark after administration of the intervention)]

Secondary outcome measures (6)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Montefiore Medical Center — The Bronx

Publications

• 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. Ther Adv Gastroenterol. 2016 Jan;9(1):98-112. doi: 10.1177/1756283X15618131. PMID 26770271
• 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
• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT06740812 · 2024-16422

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗