Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting

This study is being done to determine the efficacies of two preventative drug combinations for postoperative nausea and vomiting in patients undergoing neurosurgery. The aim of this study is to compare the efficacy of using aprepitant instead of ondansetron in combination with dexamethasone and promethazine for post-operative nausea and vomiting prophylaxis. By completing this comparison study investigators will determine the most efficacious drug combination which will allow us to enhance the overall comfort and satisfaction of neurosurgical patients in the immediate postoperative period.

Study Overview

• Status: Completed
• Conditions: Nausea; Postoperative Nausea and Vomiting (PONV)
• Intervention / Treatment: Drug: Aprepitant; Drug: Promethazine; Drug: Dexamethasone; Drug: Ondansetron

Detailed Description

One hundred-seventy-six (200) consecutive patients meeting the inclusion and exclusion criteria and who give written informed consent to participate in the study will be randomly assigned to one of two experimental groups using a 1:1 ratio. Patients in Group I will receive 25mg promethazine given intravenously (IV), 10mg dexamethasone given IV, 4mg ondansetron given intravenously, and a placebo pill given orally. Patients in Group II will receive 25mg promethazine given IV, 10mg dexamethasone given IV, 40mg aprepitant given orally, and an intravenous placebo. Thus all patients receive 25mg promethazine and 10mg dexamethasone. Group I will additionally receive 4mg ondansetron plus placebo PO and Group II will additionally receive 40mg aprepitant plus IV placebo. Because this is a double-blind study and because ondansetron is given intravenously whereas aprepitant is given orally, it is necessary to give patients an oral or IV placebo, depending on their group assignment for uniformity. Thus each patient will receive the three drugs in the PONV prophylactic triple cocktail, plus an IV or oral placebo prior to induction of anesthesia. See table below.

The following demographic and preoperative data about each patient in the two groups will be recorded:

Demographic and Preoperative Data Gender Systolic blood pressure, diastolic blood pressure, median blood pressure Age Smoking history PONV History Motion sickness history Surgery Anesthesia modality CPP Race ECG recording Hepatic function Renal function Past reactions to the study drugs

The duration of each surgery (anesthesia time) will be recorded for each patient. Patients will be continuously monitored in the post anesthesia care unit (PACU), surgical intensive care unit (SICU) and the medical floor for a total of 120 hours post operatively. Episodes of nausea, vomiting and administration of rescue therapy for either nausea or vomiting will be recorded and time stamped. In addition, the severity of the nausea or vomiting will be recorded. Nausea will be evaluated by the patient utilizing a standard verbal response scale (VRS) ranging from 0-10, 0 being no nausea and 10 being severe nausea. Vomiting will be evaluated by the investigator or nursing staff numerically as either 0, no vomiting, 1, mild vomiting, 2, moderate vomiting, or 3, severe vomiting. Rescue therapy for PONV episodes will consist of 4mg ondansetron. After the first 24hrs of starting the triple therapy antiemetic, ECG will be recorded as well as blood drawn for analysis.

Variables Primary Efficacy Variable The percentage of patients with no vomiting over 0-72 hours post operatively across the two treatment groups.

Secondary Efficacy Variables: Proportion of patients with a complete response during delayed (24-120 hours; days 2-5) and overall (0-120 hours; days 1-5) after neurological surgery and general anesthesia.

Proportion of patients with complete control, defined as no emetic episode, no need for rescue medication and no more than mild nausea overall (0-120 hours; days 1-5) after neurological surgery and general anesthesia.

Assess the severity of nausea and vomiting during acute (0-24 hours), delayed (24-120 hours) and overall (0-120 hours) intervals after neurological surgery and general anesthesia.

Assess the time to treatment failure (defined as time to first emetic episode and/or to first use of rescue medication).

Assess the time to first emetic episode.

Assess the time to significant nausea (defined as nausea rated ≥ 4 on a 0 to 10 verbal response scale or nausea that required rescue therapy).

Adverse Reactions to Treatment The incidence of any adverse reaction to treatment in the our two experimental groups will be recorded. In the ondansetron-treated patients (Group I), all cardiovascular, gastrointestinal, hepatic, integumentary and neurologic postoperative adverse events will be recorded and analyzed for cause. For instance, treatment-related diarrhea, headaches, fever, akathisia and acute dystonic reactions will be recorded and analyzed. Similarly, in the aprepitant-patients (Group II) all adverse events related to the digestive, hemic, lymphatic, nervous, cardiovascular and respiratory systems will be recorded and analyzed for cause.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical CEnter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients
• 18 to 85 years of age
• Scheduled for neurosurgery requiring opening of the cranium and dura at Ohio State University Medical Center and who consent in writing to participate in this study are eligible.

Exclusion Criteria:

• Patients will be excluded from this study if they are

  1. prisoners
  2. pregnant women
  3. mentally ill
  4. under the age of 18 or over the age of 85
  5. American Society of Anesthesiologist (ASA) classification V
  6. alcohol or drug abusers
  7. have a cerebral perfusion pressure (CPP) greater than 150 mmHg or less than 50 mmHg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aprepitant; Aprepitant is given orally, along with an oral or PO placebo depending on their group assignment for uniformity. Each patient will receive three drugs in their respective triple prophylactic medication plus an IV or oral placebo prior to induction of anesthesia. Triple therapy 40mg Aprepitant PO + IV placebo, 25mg Promethazine IV and 10mg dexamethasone IV	Drug: Aprepitant; Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction; Other Names: Emend; Drug: Promethazine; Subject will receive 25 mg of Promethazine IV around anesthesia induction; Other Names: •Pentazine; •Phenadoz; •Phenergan; •Phenergan Fortis; •Promacot; •Promethegan; Drug: Dexamethasone; Subject will receive 10 mg of Dexamethasone IV around anesthesia induction; Other Names: Decadron; Dexpak
Active Comparator: Ondansetron; Ondansetron is given via IV, along with an oral or IV placebo depending on their group assignment for uniformity. Each patient will receive three drugs in their respective triple prophylactic medication (25mg promethazine, 10mg dexamethasone, and either 4mg ondansetron or 40mg aprepitant) plus an IV or oral placebo prior to induction of anesthesia. Triple therapy 4mg Ondansetron IV + PO placebo, 25mg Promethazine IV and 10mg dexamethasone IV	Drug: Promethazine; Subject will receive 25 mg of Promethazine IV around anesthesia induction; Other Names: •Pentazine; •Phenadoz; •Phenergan; •Phenergan Fortis; •Promacot; •Promethegan; Drug: Dexamethasone; Subject will receive 10 mg of Dexamethasone IV around anesthesia induction; Other Names: Decadron; Dexpak; Drug: Ondansetron; Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction; Other Names: Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With a Complete Response/Complete Control During the First 24 Hours After Neurological Surgery Under General Anesthesia	To assess the efficacy of triple therapy with Scopolamine, Ondansetron and Dexamethasone for prevention of post operative nausea and vomiting (PONV) in high risk patients during the first 24 hours after neurological surgery under general anesthesia. - Proportion of patients with a complete response/complete control during the first 24 hours after neurological surgery under general anesthesia. Complete Control is defined as no emetic episode, no need for rescue medication and no more than mild nausea overall after neurological surgery and general anesthesia. Complete Response is defined as no vomiting and no rescue therapy after neurological surgery and general anesthesia.	24 hours post operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Operative Nausea and Vomiting (PONV) Scores on a Verbal Response Scale	To assess the efficacy of triple therapy with Scopolamine, Ondansetron and Dexamethasone for prevention of post operative nausea and vomiting (PONV) in high risk patients during a delayed period after neurological surgery under general anesthesia. - Assess the severity of nausea and vomiting during the first 24 hours after neurological surgery. Nausea is evaluated by a standard verbal response scale (VRS) ranging from 0-10, 0 being no nausea and 10 being severe nausea. Vomiting is evaluated by the investigator or nursing staff numerically as either 0, no vomiting;, 1, mild vomiting;, 2, moderate vomiting;, or 3, severe vomiting.	24 hours post-operatively

Collaborators and Investigators

• Sponsor: Sergio Bergese
• Investigators: Principal Investigator: Sergio D Bergese, M.D., Ohio State University

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 18, 2011

Study Record Updates

• Last Update Posted (Estimate): December 3, 2013
• Last Update Submitted That Met QC Criteria: November 8, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Neurosurgery
• 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; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Hypnotics and Sedatives; Anti-Anxiety Agents; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Diphenhydramine; Promethazine; Ondansetron; Aprepitant
• Other Study ID Numbers: 2007H0053