Fosaprepitant vs Metoclopramide for Nausea and Vomiting

(BARF RCT Trial)

Overseen By Mustfa K Manzur, MD MPH MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Montefiore Medical Center

Must not be taking: Antiemetics

Disqualifiers: Pregnancy, Bradycardia, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2 hours

212 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you have used antiemetics (medications to prevent nausea and vomiting) or received intravenous fluids before coming to the emergency department, you would not be eligible to participate.

What data supports the effectiveness of the drug fosaprepitant for nausea and vomiting?

Fosaprepitant is effective in preventing nausea and vomiting caused by chemotherapy, as shown in large clinical trials where it was well tolerated and worked as well as other similar treatments. It is often used with other medications to help cancer patients manage these symptoms. ^{1 2 3 4 5}

Is fosaprepitant generally safe for humans?

Fosaprepitant is generally considered safe for humans, but it can cause some side effects like hypersensitivity reactions (allergic reactions) and infusion-site reactions (irritation where the drug is injected). These side effects are usually manageable, and changes in how the drug is given can help reduce them. ^{1 2 3 4 6}

How does the drug fosaprepitant differ from other treatments for nausea and vomiting?

Fosaprepitant is unique because it is an intravenous drug that acts as a prodrug, meaning it is converted in the body to aprepitant, a neurokinin-1 receptor antagonist. This allows it to be used as an alternative to oral aprepitant, providing a different administration route for patients who may have difficulty with oral medications. ^{1 2 3 4 7}

Research Team

Benjamin W Friedman, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for adults over 18 who come to the emergency department with nausea and/or vomiting. They must be able to speak English or Spanish, have a phone for follow-up, and not be pregnant, lactating, or wanting pregnancy. Excluded are those with recent antiemetic use, bradycardia, prolonged QTc on ECG, altered mental status or dementia.

Inclusion Criteria

I went to the emergency department for nausea or vomiting.

Exclusion Criteria

Pregnancy, desiring pregnancy, or lactating

Bradycardia (< 60 bpm heart rate)

Prolonged QTc (greater than 490ms)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either fosaprepitant or metoclopramide to assess efficacy and adverse event profile

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for sustained relief from nausea and vomiting and development of new symptoms

24 hours

Follow-up assessments at 2 hours and 24 hours

Treatment Details

Interventions

• Fosaprepitant
• Metoclopramide

Trial Overview The study compares fosaprepitant's effectiveness against metoclopramide in treating nausea and vomiting. It's a double-blind RCT where neither doctors nor patients know who gets which drug. Fosaprepitant acts on the brain to block signals that cause vomiting and could be cheaper than current treatments.

Participant Groups

Group I: Investigational Intervention Experimental Treatment 1 Intervention

Fosaprepitant

Group II: Standard-of-Care Intervention Active Control 1 Intervention

Metoclopramide

Fosaprepitant is already approved in United States, European Union for the following indications:

Approved in United States as Emend for:

• Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy
• Prevention of delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy

Approved in European Union as Emend for:

• Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy
• Prevention of delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Findings from Research

Fosaprepitant is an effective antiemetic used primarily for patients undergoing moderately to highly emetogenic chemotherapy, but it can cause local injection site reactions, which are the most common infusion-related issues.

This report highlights two cases of systemic hypersensitivity reactions to fosaprepitant infusions, suggesting that while generally safe, there may be rare but serious allergic responses that healthcare providers should monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic hypersensitivity to fosaprepitant - A report of two cases. Baxley, A., Lee, Z., Medina, P.[2018]

A practice change to dilute fosaprepitant to 150 mg/250 ml and infuse it over 30 minutes significantly reduced the incidence of infusion-site reactions from 28.7% to 5.74% in cancer patients receiving the medication.

This study, which reviewed the medical records of 122 patients, suggests that the new administration method improves patient tolerance and should be considered by oncology pharmacists for better safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated report on incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant. Chau, E., Lundberg, J., Phillips, G., et al.[2019]

Intravenous fosaprepitant is an effective antiemetic for preventing nausea and vomiting in adult cancer patients undergoing highly and moderately emetogenic chemotherapy, showing good efficacy in large phase III trials with a single 150 mg dose.

Fosaprepitant is well tolerated and has a safety profile similar to that of oral aprepitant, making it a valuable addition to standard antiemetic regimens that include dexamethasone and serotonin 5-HT3 receptor antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting Associated with Chemotherapy. Garnock-Jones, KP.[2018]

Fosaprepitant, a neurokinin-1 receptor antagonist, is effective and safe for preventing chemotherapy-induced nausea and vomiting (CINV) in cancer patients undergoing highly emetogenic chemotherapy, offering a promising alternative to traditional antiemetic therapies.

As an intravenous formulation, fosaprepitant overcomes the limitations of oral aprepitant, potentially improving patient compliance and quality of life during chemotherapy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical research study for fosaprepitant to prevent chemotherapy-induced nausea and vomiting: A review. Xue, F., Liu, X., Qi, X., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Systemic hypersensitivity to fosaprepitant - A report of two cases. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Updated report on incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting Associated with Chemotherapy. [2018]

4. Poland pubmed.ncbi.nlm.nih.gov

The clinical research study for fosaprepitant to prevent chemotherapy-induced nausea and vomiting: A review. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparison between 5-day aprepitant and single-dose fosaprepitant meglumine for preventing nausea and vomiting induced by cisplatin-based chemotherapy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Benefits and Risks of Fosaprepitant in Patients Receiving Emetogenic Regimens. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant. [2021]