Antiemetic Fosaprepitant To Remedy Nausea and Vomiting
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorMontefiore Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Fosaprepitant 150 mg
DrugFosaprepitant 150mg IV administered over 15 minutes
Ondansetron 4 mg
DrugOndansetron 4mg IV administered over 15 minutes
Treatment groups
200 Participants
are divided into 2 treatment groupsGroup A: Investigational InterventionExperimental treatment 1 intervention
Group B: Standard-of-Care InterventionActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Relief from NV
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." 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, without the use or rescue medication. The number/percentage of participants who achieve relief from NV will be summarized by study arm.
Time frame
Within 2 hours of medication administration2
Occurrence of any treatment-related adverse event
The primary safety/tolerability outcome for this study is the occurrence of any treatment related adverse event (TRAE) at 2 hours of medication administration. TRAEs - not including underlying pathology causing NV - and including, but not limited to: appendicitis, small bowel obstruction, constipation, gastroparesis, gastroenteritis, gastritis, will be summarized by study arm
Time frame
2 hours following medication administration3
Requirement for additional medication
Requirement of any additional medication specifically for treatment of NV at 2 hours of medication administration; the use of rescue medications to treat persistent NV, or other medications such as additional doses or use of adjunct medications will be recorded. The number/percentage of patients who require additional medication will be summarized by study arm.
Time frame
2 hours following medication administrationSecondary outcomes
1
Freedom from nausea and vomiting (NV)
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.
Time frame
2 hours following medication administration2
Sustained Relief from nausea and vomiting (NV) (at 24 hours)
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.
Time frame
At 24-hours following medication administration3
Sustained NV Freedom (at 24 hours)
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.
Time frame
At 24- hours following medication administration4
Disposition Plan
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.
Time frame
4 hours following medication administrationOther outcomes
1
Severity of Nausea
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) such that higher scores are associated with more severe nausea. Results will be summarized by study arm.
Time frame
24 hours (measured every 15 minutes for the first 2 hours, then hourly after that until disposition; reassessed at 24 hours)2
Functional disability
Patient reported functional disability will be assessed. Functional disability will be categorized as either "Severe," "Moderate," "Mild," or "Not impaired." Categorical variables will be summarized by study arm using descriptive statistics.
Time frame
24 hours (assessed prior to receiving intervention, at 2 hour point after receiving intervention, and 24 hours after intervention)3
Number of Vomiting Episodes
The mean number of vomiting episodes per patient will be determined and summarized by study arm.
Time frame
24 hours following medication administration4
Need for rescue antiemetic medication
Binary outcome for needing or not needing additional dosing of antiemetic medication to treat nausea will be determined. Results will be summarized by study arm.
Time frame
2 hours (assessed at the 2 hour mark after administration of the intervention)Sponsors and contacts
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Source ClinicalTrials.gov