Aprepitant PO vs Ondansetron IV for Prevention of Postoperative Nausea and Vomiting

Comparison of Aprepitant PO and Ondansetron IV for Prevention of Postoperative Nausea and Vomiting (PONV) in Patients Undergoing Orthognathic Surgery and General Anesthesia.

Postoperative nausea and vomiting (PONV) persists as one of the more common complications of surgery. Although rarely life-threatening, it is the postoperative outcome that is most unfavorable to patients, even more undesirable than pain. Orthognathic surgery corrects conditions of the jaws and face related to structure, growth, sleep apnea, bad bite, or congenital malformations. The bones of the face and jaws are cut and placed in a new position. There is a high rate of PONV in orthognathic surgery (56%). It is particularly challenging to the patient as their jaws are kept closed together with wires or elastic bands. Nausea in a patient with restricted mouth opening can be psychologically unnerving and puts them at risk for fluid in their lungs.

Gan and colleagues showed a higher efficacy of aprepitant over ondansetron in preventing PONV and nausea severity after open abdominal surgery. From this study, the FDA approved the use of aprepitant for PONV prevention in patients >18 years of age. Gan suggested further investigation in different populations.

Our randomized, double-blind, prospective study will compare the efficacy of aprepitant PO versus ondansetron IV in a high risk setting for PONV: adolescents undergoing orthognathic surgery.

Our study will involve 200 consecutive, adolescent patients (ages 15-25) who will undergo at least a Le Fort 1 osteotomy (upper jaw surgery) under general anesthesia and require hospital admission for at least one night. We will exclude patients who are currently taking medications that have interactions with aprepitant (pimozide, terfenadine, astemizole, cisapride), those who have a known vomiting disorder such as bulimia, and those who have vomited for any reason within 24 hours of surgery. The procedure will be performed by 5 surgeons and general anesthesia will be administered by 3 anesthesiologists at one institution. A study coordinator, who will not be involved in the treatment, will create the randomization schedule in order to ensure blindness. The patients will be randomized to either of two groups: 1) aprepitant 40 mg PO 2) ondansetron 4 mg IV. Appropriate verbal and written consent will be obtained by the priniciple investigator or surgeon.

On the day of the procedure, all patients will receive a pill (aprepitant or aprepitant placebo) at least 1 hour prior to induction of anesthesia and an IV infusion (ondansetron or saline) over 2-5 minutes prior to intubation. The timing and doses of medications will be consistent with manufacturer's recommendations. An established protocol will ensure every patient will receive the same anesthetic regiment. Patient's fluid status will be closely monitored and hydrated appropriately according to known fluid balance calculations.

Efficacy will be assessed based on criteria set by Gan et al and will be based on the presence/absence of a vomiting episode, use of rescue medication and subjective evaluation of nausea. Patients will be monitored continuously in the PACU and on the hospital floor by the caring team (nurse, resident, anesthesiologist, surgeon) for any emetic episode or use of rescue therapy. An emetic episode is defined as an act of vomiting (oral expulsion of stomach contents) or retching (non-productive vomiting). Nausea will be assessed at intervals of 0, 2, 6, 24 hours after surgery with T0 being time of extubation. Patients will rate nausea on a 11-point verbal rating scale, with 0 being "not nausea" to 10 being "the worst nausea." Rescue medication will be offered if the patient has more than one episode of vomiting or retching, if the patient has nausea lasting longer than 15 minutes, or if the patient requests it for established nausea or vomiting.

Study Overview

• Status: Withdrawn
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: aprepitant 40 mg; Drug: ondansetron 4 mg

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center/Schneider's Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 25 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients aged 15-25 who have reached skeletal maturity and are scheduled for Le Fort 1 osteotomy as part of standard care.
• Capable of providing informed consent.

Exclusion Criteria:

• Patients with hypersensitivity to medications contraindicated with aprepitant: pimozide, terfenadine, astemizole, cisapride.
• Patients with a known vomiting disorder
• Patients who have vomited for any reason within 24 hours prior to surgery.
• Patients who are pregnant or nursing.
• Patients who are unable to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; aprepitant 40 mg + normal saline IV	Drug: aprepitant 40 mg; aprepitant 40 mg PO 1-3 hours prior to surgery; Other Names: emend 40 mg
ACTIVE_COMPARATOR: 2; placebo PO + ondansetron 4 mg IV	Drug: ondansetron 4 mg; ondansetron 4 mg IV 2-5 minutes prior to induction of anesthesia; Other Names: zofran 4 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
No vomiting and use of rescue medications	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
no nausea based on verbal rating scale	0, 2, 6, 24 hours
time to first emetic episode	24 hours
time to use of rescue medications	24 hours

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Christopher Choi, DDS, Long Island Jewish Medical Center

Publications and helpful links

General Publications

• Gan TJ, Apfel CC, Kovac A, Philip BK, Singla N, Minkowitz H, Habib AS, Knighton J, Carides AD, Zhang H, Horgan KJ, Evans JK, Lawson FC; Aprepitant-PONV Study Group. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg. 2007 May;104(5):1082-9, tables of contents. doi: 10.1213/01.ane.0000263277.35140.a3.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: June 16, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (ESTIMATE): June 18, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 8, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: PONV; ondansetron; aprepitant; orthognathic surgery; prevention of 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; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Ondansetron; Aprepitant
• Other Study ID Numbers: 07118