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

NCT ID: NCT01474915

Last Updated: 2013-12-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2013-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Postoperative Nausea and Vomiting (PONV) Nausea

Keywords

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Neurosurgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Aprepitant

Intervention Type DRUG

Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction

Promethazine

Intervention Type DRUG

Subject will receive 25 mg of Promethazine IV around anesthesia induction

Dexamethasone

Intervention Type DRUG

Subject will receive 10 mg of Dexamethasone IV around anesthesia induction

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

Group Type ACTIVE_COMPARATOR

Ondansetron

Intervention Type DRUG

Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction

Promethazine

Intervention Type DRUG

Subject will receive 25 mg of Promethazine IV around anesthesia induction

Dexamethasone

Intervention Type DRUG

Subject will receive 10 mg of Dexamethasone IV around anesthesia induction

Interventions

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Aprepitant

Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction

Intervention Type DRUG

Ondansetron

Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction

Intervention Type DRUG

Promethazine

Subject will receive 25 mg of Promethazine IV around anesthesia induction

Intervention Type DRUG

Dexamethasone

Subject will receive 10 mg of Dexamethasone IV around anesthesia induction

Intervention Type DRUG

Other Intervention Names

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Emend Zofran •Pentazine •Phenadoz •Phenergan •Phenergan Fortis •Promacot •Promethegan Decadron Dexpak

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Sergio Bergese

OTHER

Sponsor Role lead

Responsible Party

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Sergio Bergese

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Sergio D Bergese, M.D.

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Countries

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United States

Other Identifiers

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2007H0053

Identifier Type: -

Identifier Source: org_study_id