Fosaprepitant for Nausea and Vomiting

(AFTR NV RCT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Benjamin W Friedman, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Montefiore Medical Center

Must not be taking: Antiemetics

Disqualifiers: Pregnancy, Bradycardia, Dementia, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have used antiemetics or received intravenous fluids before screening.

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 oral aprepitant. It is often used with other medications like dexamethasone and serotonin blockers to help manage these symptoms in cancer patients. ^{1 2 3 4 5}

Is fosaprepitant safe for humans?

Fosaprepitant is generally safe for humans, but it can cause infusion-site reactions (like redness or swelling where the drug is given) in about 28.7% to 40% of cases. Some people may also experience hypersensitivity reactions (allergic reactions) when using this medication. ^{2 3 4 6 7}

How is the drug fosaprepitant different from other treatments for nausea and vomiting?

Fosaprepitant is unique because it is an intravenous drug that quickly converts to aprepitant in the body, allowing it to be used when oral administration is not possible. It is part of a regimen that includes other medications to prevent nausea and vomiting caused by chemotherapy, and it can be more convenient than oral options for patients undergoing highly emetogenic chemotherapy. ^{1 2 3 4 8}

Research Team

Benjamin W Friedman, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for patients experiencing nausea and vomiting who are seeking a potentially more effective treatment. Participants should not have used any other antiemetic medication recently and must be in need of immediate relief from their symptoms.

Inclusion Criteria

I am 18 years old or older.

I am experiencing nausea or vomiting.

Exclusion Criteria

Bradycardia (less than 60 bpm heart rate)

Pregnancy, desiring pregnancy, or lactating

Dementia

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either fosaprepitant or ondansetron intravenously 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 other secondary outcomes

24 hours

Continuous monitoring for 24 hours

Treatment Details

Interventions

• Fosaprepitant (Neurokinin Inhibitor)

Trial Overview The study compares the effectiveness of Fosaprepitant, a newer antiemetic drug, with Ondansetron, a standard treatment. It's randomized and double-blind, meaning neither the doctors nor patients know who gets which drug to ensure unbiased results.

Participant Groups

Group I: Investigational Intervention Experimental Treatment 1 Intervention

Fosaprepitant 150mg IV administered over 15 minutes

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

Ondansetron 4mg IV administered over 15 minutes

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Andrew D. Racine

Montefiore Medical Center

Chief Medical Officer since 1992

MD, PhD from New York University; Undergraduate degree from Harvard University

Philip O. Ozuah

Montefiore Medical Center

Chief Executive Officer since 2019

MD, PhD from New York University

Findings from Research

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]

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]

In a study of 57 patients receiving intravenous fosaprepitant for chemotherapy-induced nausea and vomiting, 40% experienced infusion site reactions, indicating a higher incidence than previously reported.

Key risk factors for these reactions included older age, the site of infusion (particularly at the back of the hand and wrist), and being a first-time recipient of fosaprepitant, all with significant statistical correlations (P < .001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Infusion Site Reactions in Peripheral Fosaprepitant Infusions. Gonçalves, SC., Sanches, SM., Bueno, CT., et al.[2018]

In a study of 868 patients receiving fosaprepitant for chemotherapy-induced nausea and vomiting, only 0.461% experienced systemic hypersensitivity reactions, aligning with the reported incidence of less than 1% in existing literature.

The findings suggest that while hypersensitivity reactions to fosaprepitant are rare, there is a need for improved education and documentation regarding these reactions to enhance patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of fosaprepitant-associated hypersensitivity reactions at a National Cancer Center. Laird, CM., Glode, AE., Schwarz, K., et al.[2020]

In a study of 81 patients receiving non-anthracycline platinum-based chemotherapy, fosaprepitant was associated with a 7.4% incidence of infusion site adverse events (ISAE), including swelling, extravasation, and phlebitis.

Patients receiving platinum-based chemotherapy experienced significantly lower rates of ISAE compared to those receiving anthracycline-based regimens, indicating that the type of chemotherapy influences the risk of adverse events related to fosaprepitant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy. Hegerova, LT., Leal, AD., Grendahl, DC., et al.[2022]

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]

References

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

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

2. Poland pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Incidence of Infusion Site Reactions in Peripheral Fosaprepitant Infusions. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Evaluation of fosaprepitant-associated hypersensitivity reactions at a National Cancer Center. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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