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

Instituto do Cancer do Estado de São Paulo

Status and phase: Enrolling; Phase 2

Conditions: Post Operative Nausea and Vomiting (PONV)

Treatments: Drug: Encapsulated amisulpride 50 mg (matched for color, weight, smell and size); Drug: Encapsulated placebo (matched for color, weight, smell and size)

Study type: Interventional

Funder types: Other

Identifiers

NCT06887621

83804424.3.0000.0083

Details and patient eligibility

About

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.

Enrollment: 276 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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276 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo ● Dexamethasone 10 mg IV immediately after anesthesia induction ● Ondansetron 4 mg IV at the end of the surgical procedure.

Treatment:

Drug: Encapsulated placebo (matched for color, weight, smell and size)

Oral Amisulpride

Experimental group

Description:

Amisulpride 50 mg ● Dexamethasone 10 mg IV immediately after anesthesia induction ● Ondansetron 4 mg IV at the end of the surgical procedure.

Treatment:

Drug: Encapsulated amisulpride 50 mg (matched for color, weight, smell and size)