Efficacy of Adding Oral Amisulpride to Dual Prophylaxis for Postoperative Nausea and Vomiting in Patients at High Risk for Nausea and Vomiting Undergoing Gynecological Surgery

Patients at High Risk for Postoperative Nausea and Vomiting Undergoing Gynecological Surgery: Efficacy of Oral Amisulpride in Combination With Intravenous Ondansetron and Dexamethasone - a Parallel-group Randomized Trial

Amisulpride is a potent antagonist of dopamine D2 and D3 receptors, both implicated in the emetic response when activated. It is currently used intravenously for the prevention of chemotherapy-induced and postoperative nausea and vomiting (PONV), but this route has a short half-life time of 4 to 5 hours, could be expensive, causes infusion-related pain, and is not available in Brazil. Some of these limitations could be overcome by the preemptive use of an oral formulation. At present, there are no data regarding the use of oral amisulpride for PONV, which is an affordable and painless option with half-life time of 12 hours. We propose a quadruple-blind clinical trial involving patients undergoing gynecological surgery aged 18 years and older, and assessed as being at high risk for PONV according to the Apfel Score (score 3 or 4). The primary outcome of this study is to evaluate complete response to PONV up to 24h, comparing the efficacy of adding 50 mg oral amisulpride as a third antiemetic agent to the standard institutional protocol at the Hospital da Mulher of São Paulo (IV dexamethasone 10 mg + IV ondansetron 4 mg) for laparoscopic surgeries. Secondary outcomes will evaluate (1) nausea, (2) vomiting, (3) nausea and vomiting, (4) use of rescue treatment, (5) overall adverse events, and (6) adverse events.

Study Overview

• Status: Active, not recruiting
• Conditions: Post Operative Nausea and Vomiting (PONV)
• Intervention / Treatment: Drug: Encapsulated placebo (matched for color, weight, smell and size); Drug: Encapsulated amisulpride 50 mg (matched for color, weight, smell and size)

• Study Type: Interventional
• Enrollment (Estimated): 276
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • Hospital da Mulher

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Laparoscopic hysterectomy to treat benign conditions.
• High risk for PONV according to the Apfel Score: scores 3 or 4.
• American Society of Anesthesiology (ASA) physical status: 1 or 2.

Exclusion Criteria:

• Cognitive or psychiatric conditions impairing consent or compliance.
• Incapability of using the mobile app MyCapp for data collection.
• History of allergy or sensibility to any medication included in the protocol: amisulpride, dexamethasone, ondansetron, fentanyl, midazolam, bupivacaine, morphine, propofol, rocuronium, sevoflurane, ephedrine, metaraminol, remifentanil, metamizole, ketoprofen, sugammadex, dimenhydrinate, pyridoxine hydrochloride, tramadol, dimethicone.
• Inability to swallow medications.
• Current use of typical or atypical antipsychotic medications.
• Gestation or lactation.
• Clinically significant cardiac arrhythmia or long QT syndrome documented.
• Hypokalemia (K+ < 3.5 mmol/L)
• Prolactin-dependent tumors.
• Pheochromocytoma.
• Parkinson's disease.
• Nausea or vomiting in the 24 hours before surgery.
• Therapeutic use of antiemetics, including corticosteroids.
• Emetogenic oncological therapy (above 10% probability of causing vomiting) in the 2 weeks before surgery.
• Persistent pre-operative hypotension on the day of surgery, defined as systolic blood pressure < 100 mmHg on at least 2 consecutive measurements.
• Mechanical ventilation plan or need for a naso/orogastric tube after surgery.
• Intestinal endometriosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo ● Dexamethasone 10 mg IV immediately after anesthesia induction ● Ondansetron 4 mg IV at the end of the surgical procedure.	Drug: Encapsulated placebo (matched for color, weight, smell and size); Placebo will be delivered orally 1 hour before anesthesia induction.
Experimental: Oral Amisulpride; Amisulpride 50 mg ● Dexamethasone 10 mg IV immediately after anesthesia induction ● Ondansetron 4 mg IV at the end of the surgical procedure.	Drug: Encapsulated amisulpride 50 mg (matched for color, weight, smell and size); Amisulpride will be delivered orally 1 hour before anesthesia induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with complete response	Complete response defined as the absence of emetic episodes (nausea, vomiting or retching) and no use of antiemetic medications.	24 hours after the end of anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first violation of the criteria for complete response	Time in minutes from the end of anesthesia until violation of criteria for complete response, defined as the absence of emetic episodes (nausea, vomiting or retching) and no use of antiemetic medications.	24 hours after the end of anesthesia
Number of participants with any nausea	Nausea (defined as unpleasant, subjective abdominal discomfort associated with the desire to vomit) measured on a 0 to 10 verbal response scale, in which 0 = no nausea at all and 10 = the worst nausea imaginable. "Any nausea" means a score ≥ 1.	24 hours after the end of anesthesia
Number of participants with vomiting	Any vomiting (expulsion of gastric contents) or dry-retching.	24 hours after the end of anesthesia
Number of participants with nausea and vomiting	Any nausea, vomiting, or dry-retching.	24 hours after the end of anesthesia
Number of Participants Receiving Rescue Medication	Rescue medication defined as an antiemetic (or other medication) given with the intention of relieving nausea and/or vomiting and/or dry-retching, or any incidental use of a drug known to have antiemetic potential	24 hours after the end of anesthesia
Total number of adverse events	Any adverse event	48 hours after ingestion of the capsule
Number of serious adverse event	Any adverse event classified as severe or life-threatening	48 hours after ingestion of the capsule
Nausea Intensity	0 to 10 scale	24 hours after the end of anesthesia

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Collaborators: University Medical Center Groningen
• Investigators: Principal Investigator: Angela M Sousa, MD, MsC, PhD, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2025
• Primary Completion (Estimated): March 29, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: March 16, 2025
• First Submitted That Met QC Criteria: March 16, 2025
• First Posted (Actual): March 20, 2025

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Postoperative Nausea and Vomiting; Laparoscopy; Amisulpride; Gynecologic Surgical Procedures
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Signs and Symptoms, Digestive; Nausea; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Vomiting; Postoperative Nausea and Vomiting; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Physical Phenomena; Light; Optical Phenomena; Nervous System Physiological Phenomena; Sensation; Weights and Measures; Smell; Color
• Other Study ID Numbers: 83804424.3.0000.0083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers. Data shared will be coded, with no PHI included.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No