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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
212
Fosaprepitant 150mg IV administered over 15 minutes
Metoclopramide 10mg IV administered over 15 minutes
Montefiore Medical Center
The Bronx, New York, United States
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.
Time frame: 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.
Time frame: 2 hours (assessed at the 2-hour mark after administration of the intervention)
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.
Time frame: 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.
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
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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: Initial presentation to disposition, approximately 4 hours
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