Post Operative Nausea and Vomiting (PONV)
Conditions
Keywords
Amisulpride, Postoperative Nausea and Vomiting, Laparoscopy, Gynecologic Surgical Procedures
Brief summary
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.
Interventions
DRUGEncapsulated amisulpride 50 mg (matched for color, weight, smell and size)
Amisulpride will be delivered orally 1 hour before anesthesia induction.
DRUGEncapsulated placebo (matched for color, weight, smell and size)
Placebo will be delivered orally 1 hour before anesthesia induction.
Sponsors
Instituto do Cancer do Estado de São Paulo
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with complete response | 24 hours after the end of anesthesia | Complete response defined as the absence of emetic episodes (nausea, vomiting or retching) and no use of antiemetic medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first violation of the criteria for complete response | 24 hours after the end of anesthesia | 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. |
| Number of participants with any nausea | 24 hours after the end of anesthesia | 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. |
| Number of participants with vomiting | 24 hours after the end of anesthesia | Any vomiting (expulsion of gastric contents) or dry-retching. |
| Number of participants with nausea and vomiting | 24 hours after the end of anesthesia | Any nausea, vomiting, or dry-retching. |
| Nausea Intensity | 24 hours after the end of anesthesia | 0 to 10 scale |
| Number of Participants Receiving Rescue Medication | 24 hours after the end of anesthesia | 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 |
| Total number of adverse events | 48 hours after ingestion of the capsule | Any adverse event |
| Number of serious adverse event | 48 hours after ingestion of the capsule | Any adverse event classified as severe or life-threatening |
Countries
Brazil
Contacts
PRINCIPAL_INVESTIGATORAngela M Sousa, MD, MsC, PhD
University of Sao Paulo
Outcome results
None listed