Antiemetic Fosaprepitant To Remedy Nausea and Vomiting

NCT06382012 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2024-15703
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nausea and Vomiting; Nausea; Vomiting

Keywords

Fosaprepitant; Vomiting; Randomized Control Trial; Ondansetron; Adults

Outcome Measures

Primary Outcomes (3)

• Relief from NV

  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." 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, without the use or rescue medication. The number/percentage of participants who achieve relief from NV will be summarized by study arm.

  Within 2 hours of medication administration

• Occurrence of any treatment-related adverse event

  The primary safety/tolerability outcome for this study is the occurrence of any treatment related adverse event (TRAE) at 2 hours of medication administration. TRAEs - not including underlying pathology causing NV - and including, but not limited to: appendicitis, small bowel obstruction, constipation, gastroparesis, gastroenteritis, gastritis, will be summarized by study arm

  2 hours following medication administration

• Requirement for additional medication

  Requirement of any additional medication specifically for treatment of NV at 2 hours of medication administration; the use of rescue medications to treat persistent NV, or other medications such as additional doses or use of adjunct medications will be recorded. The number/percentage of patients who require additional medication will be summarized by study arm.

  2 hours following medication administration

Secondary Outcomes (6)

• Freedom from nausea and vomiting (NV)

  2 hours following medication administration

• Sustained Relief from nausea and vomiting (NV) (at 24 hours)

  At 24-hours following medication administration

• Sustained NV Freedom (at 24 hours)

  At 24- hours following medication administration

• Disposition Plan

  4 hours following medication administration

• Patient Medication Preference for subsequent episode of NV

  24 hours following medication administration

Other Outcomes (9)

• Severity of Nausea

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

• Functional disability

  24 hours (assessed prior to receiving intervention, at 2 hour point after receiving intervention, and 24 hours after intervention)

• Number of Vomiting Episodes

  24 hours following medication administration

Study Arms (2)

Investigational Intervention

EXPERIMENTAL

Fosaprepitant 150mg IV administered over 15 minutes

Drug: Fosaprepitant 150 mg

Standard-of-Care Intervention

ACTIVE COMPARATOR

Ondansetron 4mg IV administered over 15 minutes

Drug: Ondansetron 4 mg

Interventions

Fosaprepitant 150 mg DRUG

Fosaprepitant 150mg IV administered over 15 minutes

Investigational Intervention

Ondansetron 4 mg DRUG

Ondansetron 4mg IV administered over 15 minutes

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 an emergency department (ED) for nausea and/or vomiting as defined by the International Classification of Diseases (ICD-10), or identified by treating clinician
• Following the approval of a protocol amendment, study patients who have received an antiemetic and remain persistently nauseated after 2 hours will be eligible to participate in the study

You may not qualify if:

• Pregnancy, desiring pregnancy, or lactating
• Antiemetic medication use less than 2 hours prior to screening
• Bradycardia (heart rate less than 60 bpm heart rate)
• Prolonged QTc (\>480ms)
• 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 (Montefiore and Weiler EDs)

The Bronx, New York, 10467, United States

RECRUITING

Related Publications (10)

• 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. Ther 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

• Tramer MR, Phillips C, Reynolds DJ, McQuay HJ, Moore RA. Cost-effectiveness of ondansetron for postoperative nausea and vomiting. Anaesthesia. 1999 Mar;54(3):226-34. doi: 10.1046/j.1365-2044.1999.00704.x.

  PMID: 10364857 BACKGROUND

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

fosaprepitant; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Benjamin W Friedman, MD MS

  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 2
• 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: April 19, 2024
• First Posted: April 24, 2024
• Study Start: November 13, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)