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.
Brief Title
Antiemetic Fosaprepitant To Remedy Nausea and Vomiting
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.
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-920-6626
Central Contact Email
mmanzur@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Nausea and Vomiting
Nausea
Vomiting
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Fosaprepitant
Nausea and Vomiting
Nausea
Vomiting
Randomized Control Trial
Ondansetron
Adults
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06382012
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2024-15703
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Antiemetic Fosaprepitant To Remedy Nausea and Vomiting
Primary Outcomes
Outcome Description
Sustained 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. The number/percentage of participants reporting each degree of nausea intensity will be summarized
Sustained 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, and then maintained at "mild" or "none" level for the entire 24-hour period following medication administration without the use of rescue medication.
Sustained 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, and then maintained at "mild" or "none" level for the entire 24-hour period following medication administration without the use of rescue medication.
Outcome Measure
Sustained Relief from NV
Outcome Time Frame
24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
Secondary Outcomes
Outcome Description
Mean severity of nausea scores will be evaluated and summarized based on a visual analogue scale from 0 to 100 (0 = no nausea, 100 = worst nausea possible)
Outcome Time Frame
24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)
Outcome Measure
Severity of Nausea
Outcome Description
Binary outcome for needing or not needing additional dosing of antiemetic medication to treat nausea will be determined
Outcome Time Frame
2 hours (assessed at the 2 hour mark after administration of the intervention)
Outcome Measure
Need for rescue antiemetic medication
Outcome Description
Participant preference for receiving the same antiemetic medication as administered for a subsequent episode of nausea and vomiting will be determined. Binary (Yes/No) responses will be summarized
Outcome Time Frame
24 hours
Outcome Measure
Medication Preference
Outcome Description
Patient reported functional disability will be assessed. Functional disability will be categorized as either severe, moderate, mild, or not impaired, and summarized
Outcome Time Frame
24 hours (assessed prior to receiving intervention, at 2 hour point after receiving intervention, and 24 hours after intervention)
Outcome Measure
Functional disability
Outcome Description
The mean number of vomiting episodes per patient will be assessed and summarized
Outcome Time Frame
24 hours
Outcome Measure
Vomiting
Outcome Description
The percentage of patients who require hospitalization within 24 hours due to NV symptoms will be determined
Outcome Time Frame
24 hours
Outcome Measure
Hospitalization
Outcome Description
The percentage of patients treated with IV fluids will be determined
Outcome Time Frame
4 hours
Outcome Measure
Fluid Treatment
Outcome Description
The mean per patient volume of IV fluids administered will be summarized
Outcome Time Frame
4 hours
Outcome Measure
Mean Fluid Volume
Outcome Description
Mean length of stay, defined as the interval of time from initial presentation to disposition, will be determined
Outcome Time Frame
Initial presentation to disposition, approximately 4 hours
Outcome Measure
Length of Stay
Outcome Description
Mean QTc durations, as calculated from ECG readings administered prior to receiving intervention and at disposition, will be determined. Prolonged QT interval is commonly associated with antiemetics and can often be a prelude to cardiac dysrhythmias associated with mortality
Outcome Time Frame
Prior to Intervention and at disposition, approximately 2 hours
Outcome Measure
QTc Interval (QT interval corrected for heart rate)
Outcome Description
Revisit rate will be assessed as the number/percentage of participants requiring a revisit to the Emergency department for NV
Outcome Time Frame
24 hours
Outcome Measure
Revisit Rate
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Friedman
Investigator Email
befriedm@montefiore.org
Investigator Phone
646-265-6415