A Pilot Study to Evaluate Barhemsys for the Prevention of Postoperative Nausea and Vomiting in the Bariatric Surgery Population
- Conditions
- Post Operative Nausea and Vomiting
- Interventions
- Drug: Amisulpride IV TreatmentDrug: Amisulpride IV PreventionDrug: Placebo PreventativeDrug: Placebo Treatment
- Registration Number
- NCT06585540
- Lead Sponsor
- Benaroya Research Institute
- Brief Summary
The purpose of this study is to evaluate the drug, Barhemsys (Amisulpride), on Postoperative Nausea and Vomiting following Bariatric surgery. Postoperative nausea and vomiting is any nausea or vomiting that occurs within 24 hours following surgery.
Barhemsys is approved for the treatment and prevention of Postoperative Nausea and Vomiting in the United States by the U.S. Food and Drug Administration (FDA).
You are being asked to take part in this study because you are going to receive anesthesia and nausea medication for your bariatric surgery. General anesthesia is used to put a person in a deep sleep, so they do not feel pain during surgery.
If you choose not to participate in the study, you and your doctor will discuss which nausea medications will be provided to you under general anesthesia. If you do participate in the study, you will be randomly assigned (like flipping a coin) into one of two groups, but you won't be told which group you are in:
* Group A will receive anesthesia and nausea medications that include dexamethasone, ondansetron, propofol and the study drug, Barhemsys
* Group B will receive anesthesia and nausea medications that include dexamethasone, ondansetron, and propofol. Group B patients will not receive Barhemsys during anesthesia. Instead, Group B will receive a placebo. A placebo is a substance that is made to look like a drug but has no drug in it. This is so that no one knows you are in Group B.
If you have Nausea after your surgery and you are in Group B, you may receive Barhemsys as a treatment or an additional placebo treatment. Half of group B is expected to receive Barhemsys and half will receive Placebo. If you continue to have nausea you will be provided additional medication to treat your symptoms. You will not be denied medications that are part of the standard of care for treating nausea following surgery.
If you participate in this study, researchers will:
Evaluate your medical history to make sure you are eligible to participate. Randomly assign you to either the group receiving anesthesia with Barhemsys or to the group receiving anesthesia without Barhemsys Collect information about your health before, during and after your bariatric surgery.
Collect information about your nausea and the nausea medications you are prescribed as part of your normal care after your surgery.
Your direct participation is expected to last for 24 hours after your surgery. Researchers may continue to access your medical records to follow how you are doing and audit data.
Risks:
All general anesthetics have some risk of reaction to medications given. Barhemsys is part of a class of medications that can cause chills, low potassium, low blood pressure or abdominal distension.
Patients in the placebo group may experience more nausea. There is a risk of loss of confidentiality of your information. You will read about the steps we take to help keep your information private and secure later in this form.
If you agree to take part in this study, and receive the study drug, Barhemsys, there may be a direct benefit to you as the study drug may be more effective at treating post surgery nausea and vomiting following bariatric surgery. We hope the information learned from this study will benefit other people who undergo Bariatric Surgery in the future.
Taking part in this study is voluntary, and you may choose not to take part or may leave the study at any time. Choosing not to take part or leaving the study will not result in any penalty or loss of benefits to which you are entitled outside of this research.
- Detailed Description
Nausea and vomiting are two of the most common adverse events following general anesthesia with an incidence of 30% in the general population and 80% in high-risk individuals1. In the bariatric surgical population PONV has been reported to affect nearly 80% of this surgical population, with one study showing nearly 60% PONV rates despite adequate prophylaxis. Postoperative Nausea and Vomiting (PONV) is a large patient dissatisfier and contributes to increased post-anesthesia care unit (PACU) length of stay, unanticipated hospital admissions, and increased healthcare costs. Research has shown that 30% of high-risk individuals will experience PONV despite adequate prophylaxis. Current PONV research endorses providing multiple antiemetics that have mechanisms of action at multiple separate receptors to reduce the risk of PONV.
Prevention of Post-operative nausea and vomiting is particularly important in high-risk surgeries when PONV can be associated with significant morbidity. Bariatric surgery is one instance where retching or emesis in the immediate postoperative period can have detrimental effects on the surgical anastomosis. Current literature supports the use of Barhemsys to prevent and treat PONV in the general surgical population6, however, the use of Barhemsys in high-risk bariatric surgeries is a major area lacking in research and evidence-based treatment. Barhemsys is the only FDA approved drug approved for the treatment and prevention of PONV.
The goal of this study is to assess the effectiveness of Barhemsys as a PONV preventative in a high-risk surgical population at distinct timepoints-first during induction of anesthesia, second following bariatric surgery, as measured by subject reported nausea or vomiting, or use of rescue antiemetics during PACU stay and within 24 hours following their surgical procedure, overall subject satisfaction, and PACU length of stay.
Prospective, randomized, subject blinded, placebo-controlled crossover pilot study.
Primary Arm: This pilot study will utilize a randomized, subject-blind, placebo-controlled crossover trial design to evaluate the efficacy of Barhemsys in preventing PONV in bariatric surgery patients at a single surgery site, Virginia Mason Medical Center. Anesthesia providers (Certified Registered Nurse Anesthetists, Physicians) will not be blinded due to subject care, nausea control is the most effective when you use drugs from different classes, not knowing the drug previously provided to subjects will prevent optimal nausea control and prevention. Research staff, performing subject observations, and subjects will be blinded to the study medications. Subject pre-screening will include a review of the subject's health history and current medications. Those subjects meeting criteria and consenting to participate, will be randomized in a 1:1 fashion to one of two groups with a computer-generated arm assignment.
Participants will be randomly assigned to either Group Barhemsys (the experimental group), receiving Barhemsys plus standard nausea prophylaxis, or Group Placebo (the placebo group) receiving saline solution (1 mL IV) and standard nausea prophylaxis during general anesthesia. Randomization will occur every Friday evening prior to planned OR cases for the following week. The study drug will be distributed and controlled by our investigational pharmacy. Placebo (1 mL NS IV) will be located in each operating room location. Barhemsys (5mg IV, Group Barhemsys) or placebo (1 mL NS IV, Control Group) will be administered at induction of general anesthesia7.
Subjects in Group Barhemsys and Group Placebo (Group Placebo-Barhemsys, and Group Placebo-Placebo will receive standard nausea prophylaxis with:
Dexamethasone 4mg IV immediately following the induction of anesthesia. Propofol infusion throughout the surgical procedure at a rate of 50mcg/kg/min stopped 15 minutes prior to the end of the surgical procedure.
Ondansetron 4mg IV 10 minutes prior to extubation.
Secondary Arm: Subjects in Group Placebo will be eligible for crossover into the Secondary Arm of the study. Randomization in the Secondary Arm will occur after initial randomization in the Primary Arm. Staff members (Nurses, Physicians) will not be blinded due to subject care, nausea control is the most effective when you use drugs from different classes, not knowing the drug previously provided to subjects will prevent optimal nausea control and prevention. Research staff, performing subject observations, and survey administration, will be blinded to the study medications.
Subjects in the Secondary Arm will be randomized to receive either Barhemsys (10 mg IV, Group Placebo-Barhemsys) or placebo (2mL Normal Saline IV, Group Placebo-Placebo) as first line treatment of PONV in the PACU. For the Secondary Arm, Barhemsys or Placebo can be administered at any time while the subject is physically located in the PACU. If nausea persists after PONV treatment with Barhemsys or placebo, subjects will then be offered additional PONV treatment medications based on subject history within 5 minutes after first line treatment. The study drug will be distributed and controlled by our investigational pharmacy. Placebo will be located at the subject bedside (2mL NS IV).
Investigators will observe subjects in the PACU and at 24 hours (+/- 6 hours) following their surgery to formally evaluate the subjects Nausea Severity (numerical rating scale), Satisfaction with nausea control, Overall Satisfaction, and side effects from Barhemsys. All other clinical outcomes and demographic subject information will be extracted from the electronic medical record.
Primary Objective: The Primary Objective of this study is to determine whether a preventative dose of Barhemsys administration reduces the incidence of PONV in the Post-Anesthesia Care Unit following bariatric surgery.
Secondary Objectives:
* Incidence of complete response to established PONV: Effectiveness of Barhemsys in the treatment of established nausea or vomiting in the high-risk bariatric surgical population during PACU stay. Failure of complete response is defined as subject reported nausea, subject emesis or use of rescue medication during PACU stay.
* PONV: Use of rescue antiemetics or subject reported nausea or vomiting within 24 hours of surgery completion.
* Nausea severity with preventative dosing of Barhemsys vs control in the PACU following bariatric surgery and at 24 hours.
* Nausea Severity reduction with treatment dosing of Barhemsys vs placebo (NRS) in the PACU following bariatric surgery and at 24 hours.
* Incidence of subject sedation and extrapyramidal symptoms in the PACU and at 24 hours as scored by the Richmond Agitation-Sedation Scale (RASS) and Barnes Akathisia Rating Scale (BARS).
* Overall subject satisfaction with PONV control presented in Likert Scale in PACU and at 24 hours. (PONV Satisfaction Survey)
* Mean/Median amount of antiemetics utilized in the PACU and within 24 hours following surgery completion.
* Mean/Median length of PACU stay, defined as time until ready for PACU discharge.
* Mean/Median length of hospital stay, defined as time until subject discharge
Inclusion Criteria:
The study will recruit adult patients (Age 18-65) scheduled for bariatric surgery. Additional inclusion criteria include ASA class I-III and patients who plan to be inpatient for at least 24 hours.
Included Surgical Procedures:
Robotic, Laparoscopic or Open Roux-en-Y Robotic, Laparoscopic or Open Gastric Sleeve Robotic, Laparoscopic or Open Gastrectomy Robotic, Laparoscopic or Open Revision Gastric Bypass
Exclusion Criteria:
Congenital QTc abnormalities current use of droperidol Parkinson's disease Allergy to Barhemsys (Amisulpride) Patient is pregnant or breastfeeding GFR \< 30 mL/min/1.73m2 Emergency surgery and add-on cases will be excluded from the study
Test Product:
Barhemsys NDC (10mg/2mL vial) 71390-0125-50
Primary Arm (Group Barhemsys):
Barhemsys 5mg IV Product will be administered intravenously at the start of the surgical procedure approximately 15 min after subject intubation. There is no repeat dosing for this medication.
Secondary Arm (Group Placebo-Barhemsys):
Barhemsys 10mg IV Product will be administered intravenously in the PACU as first line treatment of nausea. There is no repeat dosing for this medication. Those who receive Barhemsys intraoperatively in Group Barhemsys will not be eligible for rescue dose of Barhemsys in PACU. There is no repeat dosing for this medication.
Control Product:
Primary Arm:
Group Placebo (Group Placebo-Placebo and Group-Barhemsys) will receive standard nausea prophylaxis following protocol. Primary Arm subjects receiving placebo will receive 1cc normal saline on induction of anesthesia as placebo.
Secondary Arm:
Group Placebo-Placebo will receive 2cc normal saline administered intravenously during PACU stay as first line treatment of nausea in Group Placebo-Placebo only.
Duration of Subject Participation:
Subjects will be in the study for 24 hours following completion of their surgery.
Screening: Up to 7 days prior to day of surgery. Baseline demographic data will be collected at this time. Missing data will be collected on the day of surgery.
Treatment: Primary Arm: Day of surgery, at induction of anesthesia. Secondary Arm: Day of Surgery while the subject is in the Post Anesthesia Care Unit.
Follow-up: Subjects will be in the study for 24 hours (± 6 hours) following completion of their surgery. The total duration of the study is expected to be 14 months for recruitment and final subject follow-up.
Concomitant Medications:
Allowed: All subjects should be maintained on their current medications throughout the entire study, as medically feasible.
Prohibited: Preoperative Haloperidol or Droperidol due to medication interactions. Haloperidol may be utilized in the control group following surgery if they are not at risk at receiving Barhemsys.
Primary Endpoint:
Incidence of complete response of PONV in the PACU: Effectiveness of Barhemsys vs placebo in preventing PONV in the PACU following bariatric surgery. Failure of complete response is defined as subject reported nausea, subject emesis, or use of rescue medication during PACU stay.
Secondary Endpoints:
Incidence of complete response to established PONV: Effectiveness of Barhemsys in the treatment of established nausea or vomiting in the high-risk bariatric surgical population during PACU stay. Failure of complete response is defined as subject reported nausea, subject emesis, or use of rescue medication during PACU stay.
PONV: Use of rescue antiemetics or subject reported nausea or vomiting within 24 hours of surgery completion.
Nausea Severity reduction with treatment dosing of Barhemsys vs placebo (NRS) in the PACU following bariatric surgery and at 24 hours
Nausea severity with preventative dosing of Barhemsys vs placebo in the PACU following bariatric surgery and at 24 hours
Incidence of subject sedation and extrapyramidal symptoms in the PACU and at 24 hours as scored by the Richmond Agitation-Sedation Scale (RASS) and the Barnes Akathisia Rating Scale (BARS).
Overall subject satisfaction with PONV control presented in Likert Scale in PACU and at 24 hours.
Mean/Median amount of antiemetics utilized in the PACU and within 24 hours following surgery completion.
Mean/Median length of PACU stay, defined as time until ready for PACU discharge.
Mean/Median length of hospital stay, defined as time until subject discharge
Safety Evaluation:
Barhemsys causes dose and concentration-dependent prolongation of the QT interval, although at PONV prevention and treatment doses (5-10mg IV) has not been shown to have a clinically significant effect on QT interval given alone or in combination with ondansetron.
Planned Interim Analysis: Serious adverse events will be monitored by the PI (JSL) on an ongoing basis throughout the study
Primary Statistical Analysis:
Our primary analysis, incidence of Postoperative Nausea and Vomiting (PONV) will be defined as subject reported nausea, vomiting, or use of nausea rescue medication in the PACU.
Power Analysis: An a priori power analysis was conducted to determine the minimum sample size required to test the study hypothesis in this Pilot Study. Assuming a 60% prevalence of PONV in the bariatric surgery population and a 20% reduction utilizing Barhemsys.
Results indicated the required sample size to achieve 80% power for detecting a 20% difference, at a significance criterion of α = .15, was N = 128. Bariatric surgeons at Virginia Mason Medical Center (Drs. Chang, Deal and Mallipeddi) perform approximately 300 bariatric surgeries per year. A total of 260 bariatric surgeries were performed from 01/2022-01/2023 at Virginia Mason Medical Center. The power analysis is in line with previously performed research by Dr. Chrstine Oryhan on opioid free bariatric surgery at Virginia Mason Medical Center. We plan to enroll 100 patients for this planned pilot study.
Univariate and multivariate regression models will be created to identify independent risk factors for PONV and to evaluate the effect of the study drug after controlling for demographic factors such as age, sex, prior history of motion sickness, prior history of PONV, and intraoperative factors such as use of inhaled anesthetic agents and opioid medication.
The proportion of subjects experiencing PONV in the PACU will be calculated for both the experimental and control groups. The primary analysis will involve a chi-square test or Fisher\'s exact test, depending on the sample size and expected frequencies, to compare the incidence rates between the two groups. Additionally, logistic regression analysis will be performed to adjust for potential confounding factors (e.g., age, gender, comorbidities)
Severity of PONV:
The severity of PONV episodes will be evaluated using a Numerical Rating Scale (NRS). The mean severity scores between the experimental and control groups will be compared using independent t-tests or Mann-Whitney U tests if the data is non-normally distributed. Prior research has shown a good correlation between NRS and VAS8 when looking at subject reported nausea.
Subject Satisfaction (Likert Scale):
Subject satisfaction will be assessed using a Likert scale questionnaire ranging from 'very satisfied' to 'very dissatisfied'. The median scores for subject satisfaction will be calculated for each group, and the distribution of responses across different categories will be examined. The Mann-Whitney U test or ordinal logistic regression analysis will be used to compare subject satisfaction scores between the experimental and control groups. Adjustments for confounding factors will also be performed.
Missing Data and Sensitivity Analysis: In case of missing data, appropriate strategies like multiple imputation or sensitivity analysis will be employed to assess the impact of missingness on the results. Sensitivity analyses will help determine the robustness of the findings and address potential biases associated with missing data.
Statistical Software and Significance Level:
All statistical analyses will be performed using a suitable statistical software package (e.g., SPSS, R). A two-tailed p-value of less than 0.05 will be considered statistically significant.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 100
- The study will recruit adult patients (Age 18-65) scheduled for bariatric surgery. Additional inclusion criteria include ASA class I-III and patients who plan to be inpatient for at least 24 hours.
Included Surgeries:
Robotic, Laparoscopic or Open Roux-en-Y Robotic, Laparoscopic or Open Gastric Sleeve Robotic, Laparoscopic or Open Gastrectomy Robotic, Laparoscopic or Open Revision Gastric Bypass
- Pregnant or breastfeeding
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Congenital QTc abnormalities
- Current use of droperidol
- Parkinson's disease
- Allergy to Barhemsys
- GFR < 30 mL/min/1.73m2
- Emergency surgery or add-on cases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Group Placebo Barhemsys Amisulpride IV Treatment 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 Barhemsys Amisulpride IV Prevention Interventional arm receiving Barhemsys during surgery Group Placebo Placebo Preventative Placebo arm receiving Placebo during surgery Group Placebo Placebo Placebo Treatment 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
- Primary Outcome Measures
Name Time Method Number of Participants With "Complete Response" in the Post Anesthesia Care Unit Until Patient Leaves Post Anesthesia Care Unit (60-120 minutes) Complete response is defined as no occurrence of vomiting or retching, no nausea score ≥ 1 and no use of rescue medication during their Post Anesthesia Care Unit stay.
- Secondary Outcome Measures
Name Time Method Number of Participants with no Emesis Up to 24 hours following surgery Emesis is defined as vomiting (production of even the smallest amount of stomach contents) or retching (muscular movements of vomiting but without expulsion of stomach contents, usually because of an empty stomach)
Incidence of complete response to established Post-operative Nausea and Vomiting Until Patient leave Post Anesthesia Care Unit (60-90 minutes) Effectiveness of Barhemsys in the treatment of established nausea or vomiting in the high-risk bariatric surgical population during Post Anesthesia Care Unit stay. Failure of complete response is defined as subject emesis or use of rescue medication during Post Anesthesia Care Unit stay following a treatment dose of Barhemsys.
Number of participants with no nausea Up to 24 hours following surgery Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. "No nausea" means no score ≥ 1.
Number of Participants With no Use of Rescue Medication Up to 24 hours following surgery Any agent given in the post-operative period with the intention of providing anti-emetic rescue is counted as rescue antiemetic medication for the purposes of efficacy determination, even if it did not achieve control of emesis or was given incorrectly (e.g., wrong dosage or route). Any agent given in the postoperative period which would be expected, by virtue of its pharmacology, dosage, and route, to exert a clinically meaningful antiemetic effect was considered as rescue antiemetic medication, even if administered inadvertently or without the intention of providing rescue.
The Number of Participants With no Emesis, no Significant Nausea, and no Use of Rescue Medication Up to 24 hours following surgery No occurrence of vomiting/retching, no nausea score ≥ 4 on verbal response scale (where 0=no nausea at all and 10=the worst nausea imaginable) and no use of rescue medication.
The Number of Participants With no Significant Nausea Up to 24 hours following surgery Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. "No significant nausea" means no score ≥ 4.
Trial Locations
- Locations (1)
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States