Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting
Information source: Ohio State University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Postoperative Nausea and Vomiting (PONV); Nausea
Intervention: Aprepitant (Drug); Ondansetron (Drug); Promethazine (Drug); Dexamethasone (Drug)
Phase: Phase 4
Sponsored by: Sergio Bergese
Official(s) and/or principal investigator(s):
Sergio D Bergese, M.D., Principal Investigator, Affiliation: Ohio State University
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.
Official title: Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Proportion of Patients With a Complete Response/Complete Control During the First 24 Hours After Neurological Surgery Under General Anesthesia
Secondary outcome: Post Operative Nausea and Vomiting (PONV) Scores on a Verbal Response Scale
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
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.
Minimum age: 18 Years.
Maximum age: 85 Years.
- 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
- Patients will be excluded from this study if they are
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
Locations and Contacts
The Ohio State University Wexner Medical Center, Columbus, Ohio 43210, United States
Starting date: June 2007
Last updated: November 8, 2013