Clinical trial NCT06740812: Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide
Official title: Broadening Antiemetics Research by Comparing the Effectiveness of Fosaprepitant and Metoclopramide: A Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Nausea and Vomiting
Nausea
Vomiting
Keywords: Signs and Symptoms, Digestive
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Fosaprepitant
Aprepitant
Dopamine Receptor Antagonist
Randomized Control Trial
Metoclopramide
Adults
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 212
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 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.

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 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.

Eligibility criteria: Inclusion Criteria:

* Adults at least 18 years old
* Present to ED for treatment of 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 presenting to ED for evaluation and management
* Bradycardia (\< 60 bpm heart rate)
* Prolonged QTc (greater than 490ms)
* Not conversant in English or Spanish
* Altered mental status
* Dementia
* Lack of phone for follow-up communication

Primary outcomes:
measure: Sustained Nausea and Vomiting (NV) Relief
timeFrame: 2 hours (assessed at the 2-hour mark after administration of the intervention)
measure: Development of New Symptom
timeFrame: 2 hours (assessed at the 2-hour mark after administration of the intervention)
Secondary outcomes:
measure: Sustained NV Relief
timeFrame: 24 hours following medication administration
measure: NV Relief
timeFrame: 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)
measure: NV Freedom
timeFrame: 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours)
measure: Sustained NV Freedom
timeFrame: 24 hours following medication administration
measure: Medication Preference
timeFrame: 24 hours
measure: Duration of ED Stay
timeFrame: Initial presentation to disposition, approximately 4 hours
Other 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: QTc Interval (QT interval corrected for heart rate)
timeFrame: Prior to Intervention and at disposition, approximately 2 hours
measure: Need for rescue antiemetic medication
timeFrame: 2 hours (assessed at the 2-hour mark after administration of the intervention)
measure: Vomiting Episodes
timeFrame: Up to 24 hours
measure: Hospitalization
timeFrame: Up to 24 hours
measure: Need for Fluid Treatment
timeFrame: 4 hours
measure: Mean Fluid Volume
timeFrame: 4 hours
measure: Revisit Rate to Emergency Department
timeFrame: 24 hours
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Benjamin Friedman, MD
role: PRINCIPAL_INVESTIGATOR
References: