A Comparison of the Efficacy of Amisulpride and Placebo in the Prevention of PONV in Patients at Moderate-to-high Risk of PONV.

Study Overview
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Brief Summary
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A comparison of the efficacy of Amisulpride and placebo in the prevention of PONV in patients at moderate-to-high risk of PONV.

Official Title
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Randomized, Double-blind, Placebo-controlled Phase III Study of Amisulpride for IV Injection as Prophylaxis Against Post-operative Nausea and Vomiting

Conditions
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PONV

Intervention / Treatment
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* Drug: Amisulpride
* Drug: Amisulpride Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: Participant understand the study procedures and methods, voluntarily participate in this trial, and sign the informed consent. Male or female patients ≥ 18 years of age and ≤75 years of age. 18<BMI≤30kg/m^2，And weigh more than 45kg Patients undergoing elective surgery(laparoscopic gynecological or abdominal surgery) under general anaesthesia requiring，and inhalation anesthesia is maintained for more than 1 hour, but patients who receive purely diagnostic surgery cannot be enrolled; Patients with at least 2 of the following risk factors for PONV: Past history of PONV and/or motion sickness Habitual non-smoking status Female sex Expected to receive opioid analgesia post-operatively American Society of Anesthesiologists (ASA) risk score I-III - Exclusion Criteria: Patients undergoing day case surgery Patients undergoing intra-thoracic, transplant or central nervous system surgery or any surgery where post-operative emesis may pose a significant danger to the patient Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block Patients who are scheduled to be transferred to the ICU after surgery; Patients who are expected to need a naso- or oral-gastric tube in situ after surgery is completed Patients who have a documented, clinically significant cardiac arrhythmia or congenital long QT syndrome（Male≥ 450 ms female≥ 460ms）. Adequate hepatic and renal function, Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2.5 x upper limit normal (ULN)，Bilirubin ≥ 1.5 x ULN，Creatinine ≥ 1.5x ULN Patients who have received Amisulpride active ingredient for any indication within the last 2 weeks Patients who are allergic to Amisulpride active ingredient or any of the excipients of Amisulpride Patients with a significant, ongoing history of vestibular disease or dizziness Intestinal obstruction Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma. Patients with pre-existing nausea or vomiting in the 24 hours before surgery Patients treated with regular anti-emetic therapy including corticosteroids Patients being treated with medications which could induce torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and other medications such as bepridil, cisapride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin Patients being treated with levodopa or other dopamine drugs Patients who are pregnant or breast feeding. Participant who has a history of drug or alcohol abuse within 6 months before randomization Patients diagnosed with Parkinson's disease ，Patients with a history of epilepsy. Patients who have received anti-cancer chemotherapy in the previous 4 weeks of surgery Patients who have participated in other clinical research trials within 3 months before randomization Participant who may increase study-related risks or interfere with the interpretation of study results in the opinion of the investigator, who are considered unsuitable for enrollment by the investigator and/or the sponsor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Amisulpride at 5mg was given by slow iv administration during1 to 2 min at induction of anesthesia | Drug: Amisulpride<br>* 5mg/2ml<br>|
| Placebo Comparator: Placebo<br>Placebo was given by slow iv administration during1 to 2 min at induction of anesthesia | Drug: Amisulpride Placebo<br>* 2ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint was the composite measure complete response | defined as no episodes of emesis (vomiting or retching) and no use of rescue medication in the first 24h after wound closure | 24 hours after the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of no Nausea | Count of patients experiencing an episode of no nausea scored < 1 of 0-10 verbal response scale during the 24 hours period after the completion of surgery | 24 hours after end of surgery | 
| Incidence of moderate and severe Nausea | Count of participants with nausea score > 4 on 0-10 verbal response scale | 24 hours after end of surgery | 
| Incidence of Emesis (Vomiting/Retching) | An assessment of a participant experiencing an episode of emesis (vomiting/ retching) during the 24hours after the completion of the surgery | 24 hours after end of surgery | 
| Use of Rescue Medication |  | 24 hours after end of surgery | 
| Time to First Violation of Criteria for PONV | Criteria for PONV are any episode of emesis or use of rescue medication in the 24 hours after the end of surgery | 24 hours after end of surgery |