Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting
Condition: Postoperative Nausea and Vomiting (PONV); Nausea
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 4

Summary: 
      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: 
      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.
    

Intervention name(s): Aprepitant; Ondansetron; Promethazine; Dexamethasone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction; Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction; Subject will receive 25 mg of Promethazine IV around anesthesia induction; Subject will receive 10 mg of Dexamethasone IV around anesthesia induction
Other intervention name(s): Emend; Zofran; •Pentazine; •Phenadoz; •Phenergan; •Phenergan Fortis; •Promacot; •Promethegan; Decadron; Dexpak
Intervention MeSH terms: Promethazine; Diphenhydramine; Dexamethasone; Ondansetron; Aprepitant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Neurosurgery