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.
Categories
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 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
Exclusion Criteria:
* 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
* 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
Exclusion Criteria:
* 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
Inclusion Criteria
Inclusion Criteria:
* 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
* 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
Gender
All
Gender Based
false
Keywords
Fosaprepitant
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
Freedom from nausea and vomiting (NV) 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." Sustained freedom from nausea and vomiting requires a patient to present with a nausea intensity of either "Severe" or "Moderate," which is then reduced by treatment to "None" within two hours of medication administration. The number/percentage of patients with freedom from nausea/vomiting (NV) will be measured every 15 minutes for the first 2 hours. The number/percentage of patients with freedom from NV at 2 hours will be summarized by study arm.
Outcome Time Frame
2 hours following medication administration
Outcome Measure
Freedom from nausea and vomiting (NV)
Outcome Description
The number/percentage of patients demonstrating relief from nausea/vomiting (NV) will be measured every 15 minutes for the first 2 hours (for assessment of the primary outcome), then during every hour up to the end of the follow up period at 24 hours. Relief from NV is defined as achieving a level of relief of either "Mild" or None" at 2 hours and maintaining that level of "Mild" or "None" for the entire 24-hour period following medication administration, without use of rescue medication. The number/percentage of participants who achieve relief from NV will be summarized by study arm.
Outcome Time Frame
At 24-hours following medication administration
Outcome Measure
Sustained Relief from nausea and vomiting (NV) (at 24 hours)
Outcome Description
Sustained freedom from nausea and vomiting (NV) 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." Sustained freedom from nausea and vomiting requires a patient to present with a nausea intensity of either "Severe" or "Moderate," which is then reduced by treatment to "None" within two hours of medication administration (corresponding secondary outcome), and maintained at this level (i.e., "None") for the entire 24-hour follow-up period, without the use or rescue medication. The number/percentage of participants who achieve sustained freedom from NV will be summarized by study arm.
Outcome Time Frame
At 24- hours following medication administration
Outcome Measure
Sustained NV Freedom (at 24 hours)
Outcome Description
A disposition determination plan will be documented at 4 hours. Patients will be categorized as either having been either "admitted," "discharged," or status "yet to be determined." Categorical data will be summarized by study arm.
Outcome Time Frame
4 hours following medication administration
Outcome Measure
Disposition Plan
Outcome Description
Medication preference will be assessed based on patient's preference for receiving the same antiemetic medication as administered for a subsequent episode of nausea and vomiting. Binary ("Yes" for having the same medication administered, "No" for request of a different medication) responses of patient preference will be summarized by study arm.
Outcome Time Frame
24 hours following medication administration
Outcome Measure
Patient Medication Preference for subsequent episode of NV
Outcome Description
ED LOS will be defined as the interval of time from initial presentation to final disposition in the ED, will be determined. Mean LOS results will be summarized by study arm.
Outcome Time Frame
From initial presentation to disposition in ED, approximately 4 hours
Outcome Measure
Emergency Department (ED) Length of Stay (LOS)
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
Locked Fields
Render the field
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
Investigator Department
Emergency Medicine
Investigator Sponsor Organization
Montefiore
Study Department
Emergency Medicine
Study Division
Not Applicable
Categories Mesh Debug
Digestive System --- SIGNS AND SYMPTOMS, DIGESTIVE
MeSH Terms
NAUSEA
VOMITING
SIGNS AND SYMPTOMS, DIGESTIVE
SIGNS AND SYMPTOMS
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
FOSAPREPITANT
ONDANSETRON
IMIDAZOLES
AZOLES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
CARBAZOLES
INDOLES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS, 3-RING