Amisulpride for Postoperative Nausea and Vomiting

Overseen By David B Auyong, Medical Doctor

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Benaroya Research Institute

Must not be taking: Droperidol

Disqualifiers: Pregnancy, Congenital QTc, Parkinson's, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of Amisulpride in treating and preventing nausea and vomiting after bariatric surgery. Participants will be divided into groups, with some receiving Amisulpride during surgery and others receiving a placebo (a harmless pill with no active drug). Participants in the placebo group may receive Amisulpride if they experience nausea after surgery. The trial seeks adults scheduled for bariatric surgery, such as gastric sleeve or gastric bypass, who will remain in the hospital for at least 24 hours. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using droperidol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Amisulpride, known as Barhemsys, is generally safe for preventing nausea and vomiting after surgery. Studies have found that patients tolerate it well. In trials comparing it to a placebo, Amisulpride effectively prevented these symptoms, whether used alone or with other treatments. The medication blocks certain brain signals that cause nausea and vomiting.

Regarding safety, the FDA has approved Amisulpride for preventing these symptoms in adults, indicating its general safety. While all medications can have side effects, those from Amisulpride are usually mild, such as dizziness or headache, and serious problems are rare.

Overall, evidence supports that Amisulpride is safe and well-tolerated by most patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PONV?

Researchers are excited about Amisulpride for treating postoperative nausea and vomiting because it offers a novel approach compared to standard treatments like ondansetron and dexamethasone. Amisulpride works as a selective dopamine D2 and D3 receptor antagonist, targeting different pathways than typical antiemetics that often focus on serotonin receptors. This unique mechanism may provide effective relief for patients who don't respond well to current options. Additionally, its potential for rapid action during and after surgery could make it a valuable tool for improving patient comfort and recovery.

What evidence suggests that Amisulpride might be an effective treatment for postoperative nausea and vomiting?

Research has shown that amisulpride effectively prevents and treats postoperative nausea and vomiting (PONV). In this trial, participants in the experimental arm will receive Barhemsys, a form of amisulpride, during surgery. Studies have found that administering a low dose of amisulpride through an IV is safe and more effective than a placebo for managing PONV. For patients more likely to experience PONV, amisulpride effectively reduces nausea and vomiting. It also serves successfully as a backup treatment when other treatments fail. Overall, amisulpride consistently demonstrates its ability to manage and prevent PONV symptoms. ^{1 4 6 7 8}

Who Is on the Research Team?

Justin S Liberman, Medical Doctor

Principal Investigator

Virginia Mason Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-65 scheduled for bariatric surgery (like gastric bypass or sleeve gastrectomy) can join this study. They should be in good enough health for surgery (ASA class I-III) and plan to stay in the hospital at least a day after.

Inclusion Criteria

I have had or am planning to have weight loss surgery.

I am between 18 and 65 years old, scheduled for weight loss surgery, and will stay in the hospital for at least a day.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous dose of Amisulpride or placebo at the induction of anesthesia

1 day

1 visit (in-person)

Post-Anesthesia Care Unit (PACU)

Participants who initially received placebo may receive Amisulpride or placebo as first line treatment for PONV

60-120 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness of the treatment for up to 24 hours following surgery

24 hours

What Are the Treatments Tested in This Trial?

Interventions

• Amisulpride

Trial Overview The trial is testing Amisulpride, given through an IV, against a placebo to see if it can prevent or treat nausea and vomiting after weight-loss surgery. Participants will randomly receive either the drug or placebo.

How Is the Trial Designed?

Group I: Group Placebo Barhemsys Experimental Treatment 1 Intervention

Of patients who are members of Group Placebo they will be able to receive Barhemsys in the Post Anesthesia Care Unit if they experience nausea or emesis

Group II: Group Barhemsys Experimental Treatment 1 Intervention

Interventional arm receiving Barhemsys during surgery

Group III: Group Placebo Placebo Group 1 Intervention

Placebo arm receiving Placebo during surgery

Group IV: Group Placebo Placebo Placebo Group 1 Intervention

Of patients who are members of Group Placebo they will be able to receive Placebo in the Post Anesthesia Care Unit if they experience nausea or emesis

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

Approved in European Union as Solian for:

• Schizophrenia
• Acute psychotic episodes
• Depression

Approved in United States as Barhemsys for:

• Prevention and treatment of postoperative nausea and vomiting in adults

Who Is Running the Clinical Trial?

Benaroya Research Institute

Lead Sponsor

Trials

50

Recruited

12,300+

Virginia Mason Hospital/Medical Center

Collaborator

Trials

23

Recruited

8,500+

Published Research Related to This Trial

IV amisulpride is an effective treatment for preventing and treating post-operative nausea and vomiting (PONV) in adults, based on results from phase III trials that showed its efficacy both alone and in combination with other antiemetics.

The safety profile of IV amisulpride is comparable to that of a placebo, indicating it is well-tolerated with no significant safety concerns, making it a valuable option for patients who have not responded to other antiemetic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amisulpride: A Review in Post-Operative Nausea and Vomiting. Kang, C., Shirley, M.[2021]

In a study of 215 adult surgical patients at risk for postoperative nausea and vomiting (PONV), the D2/D3-antagonist APD421 (amisulpride) significantly reduced the incidence of PONV, particularly at a dose of 5 mg, compared to placebo.

APD421 demonstrated a safety profile similar to placebo, with no significant central nervous system or cardiac side effects, making it a promising option for PONV prophylaxis in moderate to high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial. Kranke, P., Eberhart, L., Motsch, J., et al.[2018]

Intravenous amisulpride has been approved as an effective antiemetic for preventing and treating postoperative nausea and vomiting (PONV), addressing a significant issue in surgical recovery for patients.

The review highlights that amisulpride, with a history of safe use as an oral antipsychotic, can serve as a valuable addition to PONV management, especially for patients who do not respond to standard prophylactic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacological profile of intravenous amisulpride for the treatment of postoperative nausea and vomiting. Fox, G., Kranke, P.[2022]

Amisulpride significantly improves the prevention and treatment of postoperative nausea and vomiting (PONV) compared to placebo, with a relative risk of complete response at 1.30 based on a systematic review of five studies involving 3243 patients.

The safety profile of amisulpride is comparable to that of placebo, indicating that low-dose intravenous amisulpride is a safe option for managing PONV, although further research is needed to determine the best dosing and timing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of amisulpride on postoperative nausea and vomiting: a systematic review and meta-analysis. Zhang, LF., Zhang, CF., Tang, WX., et al.[2021]

In a study involving 689 surgical patients, intravenous amisulpride significantly reduced the incidence of postoperative nausea and vomiting compared to placebo, with a complete response rate of 46.9% in the U.S. trial and 57.4% in the European trial.

Amisulpride was found to have a similar safety profile to placebo, with no significant differences in side effects such as QT prolongation or sedation, indicating it is a safe option for preventing postoperative nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Amisulpride for the Prevention of Postoperative Nausea and Vomiting: Two Concurrent, Randomized, Double-blind, Placebo-controlled Trials. Gan, TJ., Kranke, P., Minkowitz, HS., et al.[2018]

In a study involving 560 surgical patients experiencing postoperative nausea and vomiting (PONV), intravenous amisulpride at doses of 5 and 10 mg significantly improved the complete response rate compared to placebo, with 31.4% of patients in both amisulpride groups achieving no vomiting and not requiring rescue medication.

Amisulpride was found to be safe, with an adverse event profile similar to that of placebo, indicating it can be an effective treatment option for established PONV in patients who did not receive prior prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis. Candiotti, KA., Kranke, P., Bergese, SD., et al.[2023]

Amisulpride is an effective treatment for schizophrenia, showing comparable efficacy to haloperidol, risperidone, and olanzapine for patients with predominantly positive symptoms, and significantly better results than placebo for those with predominantly negative symptoms at lower doses (50-300 mg/day).

Amisulpride is generally well tolerated, with a lower incidence of extrapyramidal side effects compared to haloperidol, and it causes less weight gain than risperidone or olanzapine, making it a favorable option for both acute and long-term treatment of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amisulpride: a review of its use in the management of schizophrenia. McKeage, K., Plosker, GL.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04954365

Post Operative Nausea and Vomiting (PONV) Rescue ... PROMPT (PONV Rescue Outcomes after AMisulPride Treatment) is an observational Phase IV study designed to evaluate real-world evidence in relation to the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32274525/

Efficacy of amisulpride on postoperative nausea and vomiting Based on our findings, low-dose, intravenous amisulpride is safe and efficacious for the prevention and treatment of PONV compared to placebo.

3. barhemsys.com barhemsys.com/efficacy

Effective, proven rescue treatment for PONV in adults Amisulpride prevents postoperative nausea and vomiting in patients at high risk: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2018;128( ...

4. investor.eagleus.com investor.eagleus.com/news-releases/news-release-details/eagle-pharmaceuticals-present-abstract-post-hoc-analysis

News Details “In patients who experience PONV, nausea occurs much more frequently than vomiting. This analysis details pooled data on nausea-related outcomes ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT367238

Intravenous amisulpride as rescue treatment of ... Intravenous (IV) amisulpride has been shown to be safe and effective for the rescue treatment of Post-Operative Nausea and Vomiting (PONV) in a large, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33656662/

Amisulpride: A Review in Post-Operative Nausea and ... Results from placebo-controlled phase III trials showed that IV amisulpride is efficacious both in the prevention of PONV (used either alone or in combination ...

7. barhemsys.com barhemsys.com/

Barhemsys® (amisulpride) | Proven Antiemetic Medication ... Barhemsys is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist indicated in adults for: prevention of postoperative nausea and vomiting (PONV) ...

8. barhemsys.com barhemsys.com/impact-of-ponv

Adverse Impact of PONV | Barhemsys® (amisulpride) Nausea and vomiting in the PACU may result in1,5-8. Clinical complications of varying frequency and severity; Poor patient satisfaction; More nursing ...