Comparison of Aprepitant Versus Aprepitant and Transdermal Scopolamine for Preventing Postoperative Nausea and Vomiting

A Randomized, Double-blind Comparison of Oral Aprepitant Alone vs Oral Aprepitant and Transdermal Scopolamine for Preventing Postoperative Nausea and Vomiting

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.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: Aprepitant; Drug: Scopolamine

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.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Hahnemann University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Aprepitant; Aprepitant 40mg PO one time at least one hour prior to induction of anesthesia; Other Names: Emend; Drug: Scopolamine; Scopolamine transdermal applied to skin behind the ear one hour prior to surgery; Other Names: Scopace; Transdermal scopolamine
Placebo Comparator: Aprepitant and Scopolamine Placebo 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.	Drug: Scopolamine; Scopolamine transdermal applied to skin behind the ear one hour prior to surgery; Other Names: Scopace; Transdermal scopolamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Nausea and Vomiting	24 hours postoperatively

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Drexel University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Michael S Green, DO, Drexel University College of Medicine

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 15, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 1, 2014
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: postoperative nausea and vomiting
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiemetics; Gastrointestinal Agents; Adjuvants, Anesthesia; Mydriatics; Neurokinin-1 Receptor Antagonists; Aprepitant; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: 00659737