Clinical trial NCT06382012: Antiemetic Fosaprepitant To Remedy Nausea and Vomiting
Official title: Antiemetic Fosaprepitant To Remedy Nausea and Vomiting
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Nausea and Vomiting
Nausea
Vomiting
Keywords: Fosaprepitant
Nausea and Vomiting
Nausea
Vomiting
Randomized Control Trial
Ondansetron
Adults
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2024-04-24
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 emergency departments (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.

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.

Eligibility criteria: Inclusion Criteria:

* Adults at least 18 years old
* Present for 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 screening
* Bradycardia (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

Primary outcomes:
measure: Sustained Relief from NV
timeFrame: 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
Secondary outcomes:
measure: Severity of Nausea
timeFrame: 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
measure: Need for rescue antiemetic medication
timeFrame: 2 hours (assessed at the 2 hour mark after administration of the intervention)
measure: Medication Preference
timeFrame: 24 hours
measure: Functional disability
timeFrame: 24 hours (assessed prior to receiving intervention, at 2 hour point after receiving intervention, and 24 hours after intervention)
measure: Vomiting
timeFrame: 24 hours
measure: Hospitalization
timeFrame: 24 hours
measure: Fluid Treatment
timeFrame: 4 hours
measure: Mean Fluid Volume
timeFrame: 4 hours
measure: Length of Stay
timeFrame: Initial presentation to disposition, approximately 4 hours
measure: QTc Interval (QT interval corrected for heart rate)
timeFrame: Prior to Intervention and at disposition, approximately 2 hours
measure: Revisit Rate
timeFrame: 24 hours
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center (Montefiore and Weiler EDs)
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Benjamin W Friedman, MD MS
role: PRINCIPAL_INVESTIGATOR
References: