Nausea and Vomiting, Nausea, Vomiting
Conditions
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
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.
Interventions
DRUGFosaprepitant for Injection
Fosaprepitant 150mg IV administered over 15 minutes
Metoclopramide 10mg IV administered over 15 minutes
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Nausea and Vomiting (NV) Relief | 2 hours (assessed at the 2-hour mark after administration of the intervention) | 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. |
| Development of New Symptom | 2 hours (assessed at the 2-hour mark after administration of the intervention) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained NV Relief | 24 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 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. |
| NV Relief | 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours) | 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. |
| NV Freedom | 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until final disposition; reassessed at 24 hours) | 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. |
| Sustained NV Freedom | 24 hours following medication administration | 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. |
| Medication Preference | 24 hours | 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. |
| Duration of ED Stay | Initial presentation to disposition, approximately 4 hours | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Severity of Nausea | 24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours) | Severity of nausea will be evaluated based on responses to a visual analogue scale ranging from 0 to 100 (0 = no nausea, 100 = worst nausea possible). Mean scores will be summarized and reported by study arm. Higher scores are associated with increased severity of nausea. |
| QTc Interval (QT interval corrected for heart rate) | Prior to Intervention and at disposition, approximately 2 hours | Mean QTc durations, as calculated from electrocardiogram (ECG) readings administered prior to receiving intervention, and at disposition, will be determined. Mean QTc durations will be summarized by study arm. Prolonged QT interval is commonly associated with antiemetics and can often be a prelude to cardiac dysrhythmias associated with mortality. |
| Need for rescue antiemetic medication | 2 hours (assessed at the 2-hour mark after administration of the intervention) | The need for rescue antiemetic medication during the study will be assessed using a binary outcome (i.e., Yes: or No) to summarize whether additional dosing of antiemetic medication to treat nausea was needed. Results will be summarized by study arm using basic descriptive statistics. |
| Vomiting Episodes | Up to 24 hours | The mean number of vomiting episodes per patient over the past 24 hours will be assessed and summarized by study arm. |
| Hospitalization | Up to 24 hours | The percentage of patients who required hospitalization within 24 hours due to NV symptoms will be determined and summarized by study arm. Hospitalizations are associated with increased complications and less favorable outcomes. |
| Need for Fluid Treatment | 4 hours | The percentage of patients treated with intravenous (IV) fluids will be determined and summarized by study arm. The need for IV fluids is associated with increased supportive care, increased hospital LOS and less favorable outcomes. |
| Mean Fluid Volume | 4 hours | For patients requiring IV fluids, the mean per patient volume of IV fluids administered will be summarized and reported by study arm. The need for, and increased volumes of, IV fluids is associated with increased supportive care, increased hospital LOS and less favorable outcomes. |
| Revisit Rate to Emergency Department | 24 hours | For purposes of this study, revisit rate will be defined as the number/percentage of participants requiring a revisit to the ED for additional evaluation and management of NV. Results will be summarized by study arm using basic descriptive statistics. More frequent revisit rates are associated with increased complications and less favorable outcomes. |
Countries
United States
Contacts
Primary ContactMustfa K Manzur, MD MPH MS
Outcome results
None listed