Nausea, Vomiting
Conditions
Keywords
postoperative nausea and vomiting
Brief summary
The purpose of this study is to compare the incidence of nausea, vomiting, need for rescue medication, prolonged PACU time, and unplanned hospital admission in patients with high risk for post-operative nausea and vomiting (PONV) treated with oral aprepitant with or without transdermal scopolamine preoperatively.
Detailed description
Aprepitant, a selective antagonist of neurokinin-1 (NK-1) receptors, blocks the emetic effects of substance P. NK-1 receptors are found on vagal afferents in the gastrointestinal tract and in the nucleus tractus solitaries in the brain. Substance P action on the NK-1 receptors in the central nervous system (CNS) is one of the final pathways to an emetic response. Scopolamine antagonizes muscarinic type 1 (M1) and histamine type 1 (H1) receptors in the CNS, hypothalamus, and vomiting center. The noradrenergic system is also suppressed resulting in a diminished response to vestibular stimulation. Surgical procedures, opioids, and movement postoperatively all stimulate the vestibular system making scopolamine effective prophylaxis for PONV. In adults undergoing general anesthesia with inhalational anesthetic agents, predictive risk factors for PONV include female sex, history of PONV or motion sickness, nonsmoking status, and the use of postoperative opioids. The frequency of PONV is 10% with zero, 21% with one, 39% with two, 61% with three, and 79% with 4 risk factors. The type of surgery also plays a major role. High risk procedures include intrabdominal, laparoscopic, orthopedic, major gynecologic, thyroid, otolaryngological, neurosurgical, breast, and plastic surgery. Improving PONV prophylaxis would have a profound impact on patient care. Decreasing the incidence of nausea, vomiting, need for rescue medication, prolonged PACU time, and unplanned admissions is beneficial. Recent evidence suggests multiple drug therapy is superior to single agents. The correct preoperative treatment medication is instrumental in the outcome. This study compares the incidence of nausea, vomiting, need for rescue medication, prolonged PACU time, and unplanned hospital admission in patients with high risk for PONV treated with oral aprepitant with or without transdermal scopolamine preoperatively.
Interventions
DRUGAprepitant
Aprepitant 40mg PO one time at least one hour prior to induction of anesthesia
DRUGScopolamine
Scopolamine transdermal applied to skin behind the ear one hour prior to surgery
Sponsors
Merck Sharp & Dohme LLC
Drexel University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 65 years of age * American Society of Anesthesiology (ASA) physical status 1-3 * If on oral contraceptive, must be willing to use back up method for 1 month * Must have 2 risk factors for PONV
Exclusion criteria
* History of vomiting due to middle ear infection, nervous system disorder, or other condition * Procedure less than 1 hour * Pregnant or breast feeding * Antiemetic medication in previous 24 hours * Narrow-angle glaucoma * Allergic to belladonna alkaloids * Hypersensitive to barbiturates * Prostate hypertrophy * Severe hepatic disease * On chemotherapy taking aprepitant * Fever * Sepsis * Taking any of the following medications: Orap, Seldane, Hismanal, Propulsid, Phenytoin, Phenothiazines, Tricyclic antidepressants, Meperidine, Tolbutamide, Aluminum and Magnesium containing Antacids, Anti-cholinergics, Coumadin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Nausea and Vomiting | 24 hours postoperatively |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Nausea and Vomiting in PACU | Postoperatively, up to 2 hours |
| Total Vomiting | 24 hours postoperatively |
| Need for Antiemetic Medication | 24 hours postoperatively |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aprepitant and Scopolamine Group Patients receive aprepitant and scopolamine for prevention of postoperative nausea and vomiting then were followed through the post operative period looking for nausea, vomiting, composite, and rescue medication utilization. This was compared to patients receiving aprepitant and scopolamine placebo looking for a difference in incidence of events.
Aprepitant: Aprepitant 40mg PO one time at least one hour prior to induction of anesthesia
Scopolamine: Scopolamine transdermal applied to skin behind the ear one hour prior to surgery | 58 |
| Aprepitant and Placebo Scopolamine Group Patients receiving aprepitant and placebo scopolamine for prevention of postoperative nausea and vomiting then followed through the post operative period looking for signs of nausea, vomiting, composite, and rescue medication utilization. This was compared to patients receiving aprepitant and scopolamine looking for a difference in incidence of events.
Aprepitant: Aprepitant 40mg PO one time at least one hour prior to induction of anesthesia
Scopolamine: Placebo Scopolamine transdermal applied to skin behind the ear one hour prior to surgery | 57 |
| Total | 115 |
Baseline characteristics
| Characteristic | Aprepitant and Scopolamine Group | Aprepitant and Placebo Scopolamine Group | Total |
|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 11.06 | 47.2 years STANDARD_DEVIATION 11.27 | 46.8 years STANDARD_DEVIATION 11.17 |
| Sex: Female, Male Female | 51 Participants | 52 Participants | 103 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 58 | 29 / 57 |
| serious Total, serious adverse events | 0 / 58 | 0 / 57 |
Outcome results
Primary
Number of Participants With Nausea and Vomiting
Time frame: 24 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant and Scopolamine Group | Number of Participants With Nausea and Vomiting | 24 participants |
| Aprepitant and Placebo Scopolamine Group | Number of Participants With Nausea and Vomiting | 29 participants |
Secondary
Need for Antiemetic Medication
Time frame: 24 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant and Scopolamine Group | Need for Antiemetic Medication | 23 participants |
| Aprepitant and Placebo Scopolamine Group | Need for Antiemetic Medication | 21 participants |
Secondary
Number of Participants With Nausea and Vomiting in PACU
Time frame: Postoperatively, up to 2 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant and Scopolamine Group | Number of Participants With Nausea and Vomiting in PACU | 35 participants |
| Aprepitant and Placebo Scopolamine Group | Number of Participants With Nausea and Vomiting in PACU | 39 participants |
Secondary
Total Vomiting
Time frame: 24 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aprepitant and Scopolamine Group | Total Vomiting | 5 participants |
| Aprepitant and Placebo Scopolamine Group | Total Vomiting | 2 participants |