Official Title: “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 Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: June 2010

Intervention(s) in this Clinical Trial

• Drug: aprepitant 40 mg
  • aprepitant 40 mg PO 1-3 hours prior to surgery
• Drug: ondansetron 4 mg
  • ondansetron 4 mg IV 2-5 minutes prior to induction of anesthesia

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • aprepitant 40 mg + normal saline IV
• Active Comparator: 2
  • placebo PO + ondansetron 4 mg IV

Primary Measures

• No vomiting and use of rescue medications
  • Time Frame: 24 hours
    Safety Issue?: No

Secondary Measures

• no nausea based on verbal rating scale
  • Time Frame: 0, 2, 6, 24 hours
    Safety Issue?: No
• time to first emetic episode
  • Time Frame: 24 hours
    Safety Issue?: No
• time to use of rescue medications
  • Time Frame: 24 hours
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 25 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Shore Long Island Jewish Health System

Overall Clinical Trial Officials and Contacts

Christopher Choi, DDS Principal Investigator Long Island Jewish Medical Center  

Overall Contact: Christopher Choi, DDS 917-363-6063 drchristopherchoi@gmail.com

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00699894

Study ID Number: 07118

ClinicalTrials.gov Identifier: NCT00699894

Health Authority: United States: Institutional Review Board