Trial Outcomes & Findings for Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting (NCT NCT01474915)

Results Overview

To assess the efficacy of triple therapy with Scopolamine, Ondansetron and Dexamethasone for prevention of post operative nausea and vomiting (PONV) in high risk patients during the first 24 hours after neurological surgery under general anesthesia. \- Proportion of patients with a complete response/complete control during the first 24 hours after neurological surgery under general anesthesia. Complete Control is defined as no emetic episode, no need for rescue medication and no more than mild nausea overall after neurological surgery and general anesthesia. Complete Response is defined as no vomiting and no rescue therapy after neurological surgery and general anesthesia.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

122 participants

Primary outcome timeframe

24 hours post operatively

Results posted on

2013-12-03

Participant Flow

Recruitment was conducted at The Ohio State University Wexner Medical Center. It started in January of 2009 and ended in April of 2012.

Whenever a participant was enrolled into the study but later did not meet all the inclusion/exclusion criteria, they were excluded from the trial before assignment to groups.

Participant milestones

Participant milestones
Measure	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 Aprepitant : Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine 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 Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Ondansetron : Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine IV around anesthesia induction
Overall Study STARTED	60	61
Overall Study COMPLETED	50	51
Overall Study NOT COMPLETED	10	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aprepitant n=60 Participants 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 Aprepitant : Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine IV around anesthesia induction	Ondansetron n=61 Participants 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 Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Ondansetron : Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine IV around anesthesia induction	Total n=121 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants	47 Participants n=7 Participants	92 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Age Continuous	51.8136 years STANDARD_DEVIATION 14.7 • n=5 Participants	50.15 years STANDARD_DEVIATION 16.4 • n=7 Participants	50.9748 years STANDARD_DEVIATION 15.6062 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	28 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	33 Participants n=7 Participants	59 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants	61 participants n=7 Participants	121 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours post operatively

Population: Number of patients with Complete Control

To assess the efficacy of triple therapy with Scopolamine, Ondansetron and Dexamethasone for prevention of post operative nausea and vomiting (PONV) in high risk patients during the first 24 hours after neurological surgery under general anesthesia. \- Proportion of patients with a complete response/complete control during the first 24 hours after neurological surgery under general anesthesia. Complete Control is defined as no emetic episode, no need for rescue medication and no more than mild nausea overall after neurological surgery and general anesthesia. Complete Response is defined as no vomiting and no rescue therapy after neurological surgery and general anesthesia.

Outcome measures

Outcome measures
Measure	Ondansetron n=51 Participants Ondansetron is given via intravenous (IV), along with an oral (PO) or IV placebo depending on their group assignment for uniformity. Each patient receives 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 Dexamethasone : Subject receives 10 mg of Dexamethasone IV around anesthesia induction Ondansetron : Subject receives 4 mg of Ondansetron IV versus placebo around anesthesia induction Promethazine : Subject receives 25 mg of Promethazine IV around anesthesia induction	Aprepitant n=50 Participants Aprepitant is given orally (PO), along with an oral or PO placebo depending on their group assignment for uniformity. Each patient receives three drugs in their respective triple prophylactic medication plus an intravenous (IV) or oral placebo prior to induction of anesthesia. Triple therapy 40mg Aprepitant PO + IV placebo, 25mg Promethazine IV and 10mg dexamethasone IV Aprepitant : Subject receives 40 mg of Aprepitant versus placebo PO before anesthesia induction Dexamethasone : Subject receives 10 mg of Dexamethasone IV around anesthesia induction Promethazine : Subject receives 25 mg of Promethazine IV around anesthesia induction
Proportion of Patients With a Complete Response/Complete Control During the First 24 Hours After Neurological Surgery Under General Anesthesia Complete Control	41 participants	38 participants
Proportion of Patients With a Complete Response/Complete Control During the First 24 Hours After Neurological Surgery Under General Anesthesia Complete Response	30 participants	30 participants

SECONDARY outcome

Timeframe: 24 hours post-operatively

Population: Severity of nausea and vomiting

To assess the efficacy of triple therapy with Scopolamine, Ondansetron and Dexamethasone for prevention of post operative nausea and vomiting (PONV) in high risk patients during a delayed period after neurological surgery under general anesthesia. \- Assess the severity of nausea and vomiting during the first 24 hours after neurological surgery. Nausea is evaluated by a standard verbal response scale (VRS) ranging from 0-10, 0 being no nausea and 10 being severe nausea. Vomiting is evaluated by the investigator or nursing staff numerically as either 0, no vomiting;, 1, mild vomiting;, 2, moderate vomiting;, or 3, severe vomiting.

Outcome measures

Outcome measures
Measure	Ondansetron n=51 Participants Ondansetron is given via intravenous (IV), along with an oral (PO) or IV placebo depending on their group assignment for uniformity. Each patient receives 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 Dexamethasone : Subject receives 10 mg of Dexamethasone IV around anesthesia induction Ondansetron : Subject receives 4 mg of Ondansetron IV versus placebo around anesthesia induction Promethazine : Subject receives 25 mg of Promethazine IV around anesthesia induction	Aprepitant n=50 Participants Aprepitant is given orally (PO), along with an oral or PO placebo depending on their group assignment for uniformity. Each patient receives three drugs in their respective triple prophylactic medication plus an intravenous (IV) or oral placebo prior to induction of anesthesia. Triple therapy 40mg Aprepitant PO + IV placebo, 25mg Promethazine IV and 10mg dexamethasone IV Aprepitant : Subject receives 40 mg of Aprepitant versus placebo PO before anesthesia induction Dexamethasone : Subject receives 10 mg of Dexamethasone IV around anesthesia induction Promethazine : Subject receives 25 mg of Promethazine IV around anesthesia induction
Post Operative Nausea and Vomiting (PONV) Scores on a Verbal Response Scale Nausea episodes	1 units on a scale Interval 1.0 to 2.0	1 units on a scale Interval 1.0 to 2.0
Post Operative Nausea and Vomiting (PONV) Scores on a Verbal Response Scale Vomiting episodes	1.5 units on a scale Interval 1.0 to 3.0	1.5 units on a scale Interval 1.0 to 2.0

Adverse Events

Aprepitant

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Ondansetron

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aprepitant n=60 participants at risk 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 Aprepitant : Subject will receive 40 mg of Aprepitant versus placebo PO before anesthesia induction Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine IV around anesthesia induction	Ondansetron n=61 participants at risk 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 Dexamethasone : Subject will receive 10 mg of Dexamethasone IV around anesthesia induction Ondansetron : Subject will receive 4 mg of Ondansetron IV versus placebo around anesthesia induction Promethazine : Subject will receive 25 mg of Promethazine IV around anesthesia induction
General disorders Fever	0.00% 0/60	1.6% 1/61 • Number of events 1
Vascular disorders Deep Vein Thrombosis	0.00% 0/60	1.6% 1/61 • Number of events 1
Nervous system disorders Cerebrovascular Hematoma	3.3% 2/60 • Number of events 2	0.00% 0/61
Nervous system disorders Cerebrospinal fluid leak	0.00% 0/60	1.6% 1/61 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Andrew Otey

The Ohio State University Department of Anesthesiology

Phone: 6142933559

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place