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Prevention of Postoperative Nausea and Vomiting (PONV) in Surgical Patients

Prevention of Postoperative Nausea and Vomiting in Surgical Patients

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00757822
Acronym
PONV
Enrollment
216
Registered
2008-09-23
Start date
2009-12-31
Completion date
2015-04-30
Last updated
2016-05-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Postoperative Nausea and Vomiting

Brief summary

This study will compare two different drug regimens (oral dronabinol versus intravenous ondanseteron) for the prevention of post-operative nausea and vomiting (PONV).

Detailed description

Anesthesia has become remarkably safe during the past two decades, yet postoperative nausea and vomiting (PONV) continues to be a vexing problem with an unacceptably high incidence. Multiple factors including age, gender, type of surgery and anesthetic agents, perioperative opioid use and duration of anesthesia have been implicated in the cause of PONV. Several new drugs have been introduced during the last two decades to minimize PONV; however the incidence still remains significantly high, ranging from 30% during the first 24 postoperatively to 35% post discharge. Unrelenting PONV results in delayed discharge which is particularly significant after outpatient surgery. The proposed study will examine the anti-emetic properties of orally administered dronabinol given immediately prior to surgery with standard of care intravenous ondansetron given at the end of a surgical procedure in an effort to assess the need for cost effective prophylaxis of PONV. The chemoreceptor trigger zone (CTZ) functions as emetic chemoreceptor for the vomiting centers. Many antiemetic drugs acting at the level of the CTZ are responsible for vomiting in patients receiving chemotherapy and postoperative patients. Our regimen of oral dronabinol has been proven to reduce the incidence of PONV in patients receiving chemotherapy. We intend to prove that a regimen that has been utilized in patients receiving chemotherapeutic drugs will work in patients with a high risk for developing PONV following surgery. We hypothesize that a regimen of preoperative low dose of dronabinol is superior in efficacy to a standard antiemetic in preventing the incidence of PONV, and thus will not only improve patient satisfaction but will also reduce length of stay in patients undergoing outpatient surgery. Specific Objectives 1. Reduction of postoperative and postdischarge nausea and vomiting in ambulatory surgery patients. 2. Reduce rate of hospital admissions and length of inpatient stay after outpatient surgery. 3. Improve patient satisfaction after outpatient surgery. Procedure After informed consent, surgical patients scheduled for outpatient abdominal surgery at the Central Arkansas Veterans Healthcare System (CAVHS) who are at high risk for developing PONV following their procedure will be randomized to receive either the study drug ( preoperative oral dronabinol-5 mg) or standard therapy ( 4 mg ondansetron intravenously at the end of surgery). The outcome measures will be the presence or absence of PONV, the severity and number of such episodes, the event count of rescue antiemetic use and patient satisfaction. All data will be recorded by personnel who are blinded to the drug regimen. Relevance: At CAVHS, 2/3 of our patients are scheduled for outpatient surgical procedure everyday. Our regimen will minimize postoperative and postdischarge nausea and vomiting, improve post-operative care unit (PACU) length of stay, minimize unnecessary hospital admissions, provide patient satisfaction and cost containment. The potential for application of this inexpensive intervention to other surgeries is enormous. Reducing the incidence of PONV could have a significant impact on patient satisfaction. The intervention is very low-risk, efficacious, and could substantially impact on the experience and the outcome of the Veteran undergoing surgery.

Interventions

DRUGDronabinol

Dronabinol (5mg) will be administered orally (p.o.) 20-60 min pre-operatively.

DRUGOndansetron

Ondansetron (4mg) will be administered intravenously (iv) intraoperatively in those patients not receiving Dronabinol.

Sponsors

VA Office of Research and Development
Lead SponsorFED

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* The patients undergoing outpatient operations for intra-abdominal or abdominal wall procedures (e.g. hernias) under general anesthesia. * Patients that are at increased risk for PONV based on the Koivuranta risk scoring system, with inclusion of patients having a Koivuranta risk score (K score) of 2 or more. * Ability to give informed consent. * Veteran eligible for treatment.

Exclusion criteria

* Patients \<18 years old * Patients with a history of hypersensitivity to cannabinoids or sesame oil --Patients with current substance abuse. Substance abuse will be identified meeting one or both of the following criteria: * a) Review the participant's medical chart to identify inpatient, residential, or outpatient treatment for alcohol or drug dependence as recorded in the Veterans Health Administration Computerized Patient Record system (CPRS) within the preceding six months. OR * b) Patient report. Exclude patients who report current marijuana or cocaine use within the past 30 days. If a drug screen is clinically indicated and is positive the patient will NOT be entered into the study. * Patients taking medications known to have significant drug-drug interactions with the prescribed drug and study drugs, Dronabinol and Ondansetron, will be reviewed in Micromedex. Micromedex is a medication database used by Central Arkansas Veterans Healthcare System (CAVHS). If the drug could have a drug-drug interaction with either dronabinol or ondansetron the patients will NOT be entered into the study. If a drug is confirmed via Micromedex not to have a drug-drug interaction, the patient will be eligible for study participation. * Pregnant women * Patients with prolonged QTC intervals on electrocardiogram (EKG). * Patients enrolled in another clinical trial at the time of randomization. * Inability to adhere to study protocol

Design outcomes

Primary

MeasureTime frameDescription
Incidence of Postoperative Nausea and VomitingPost-operative Care Unit (PACU) length of stay on day of surgery (time from end of surgery to transfer to discharge unit or other hospital unit)The incidence of postoperative nausea (PON) and postoperative vomiting (POV) was assessed during Post-operative Care Unit (PACU) stay.
Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScalePost-operative Care Unit (PACU) stay from end of surgery to transfer to ambulatory unitVAS Scale: 0=no nausea, 1-3=mild nausea, 4-6= moderate nausea, 7-9= severe nausea, 10=extreme nausea usually accompanied with vomiting. VAS nausea score were obtained every 30 min from entry into post-operative care unit (PACU) for first 2 hrs. and then hourly until time of transfer out of PACU.
Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery24-48 hrs post surgeryParticipants were queried for presence of postoperative nausea (PON) or postoperative vomiting (POV) during the 24-48 hr window post surgery.

Secondary

MeasureTime frameDescription
Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or VomitingPost operative follow up interviews 24 hrs to 6 wksPercent of participants who responded that they would be willing to take preemptive medication for nausea and vomiting for subsequent surgeries when queried during post-operative follow-up interviews at 24-48 hrs or 2-6 weeks.
Post-Operative Care Unit Length of Stay (Min)Day of surgery (time from end of surgery to transfer to ambulatory pre-discharge unit or other unit)Length of time in PACU (minutes) measured from end of surgery to time of transfer to ambulatory care prior to home discharge or time to hospital admission if applicable.
Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive MedicationPost-operative follow-up interviews 24 hr to 6 weeks post surgeryPercent of participants willing to pay extra money for preemptive medication for PONV for subsequent surgical procedures when queried at post-operative 24-48 hr. and at 2-6 wk. follow-up interviews.
Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedurePost-operative Day of Surgery (DOS)Number of all-cause hospital admissions on day of elective out-patient surgery .
Post-operative Antiemetic UseEnd of surgery to 48 hr post surgeryPercentage of participants requiring post-operative anti-emetic medications.. Anti-emetic medication need was assessed during a) post-operative care unit (PACU) stay and b)during the first 48 hrs. following discharge from PACU to home or if applicable to in-patient unit.

Countries

United States

Participant flow

Recruitment details

Recruitment period was from 12-02-2009 to 11-20-2013. Participants were recruited during pre-surgery or preanesthesia clinic visits for elective outpatient abdominal surgery lasting at least 1 hr. Inclusion criteria included high risk for post-operative nausea and vomiting (PONV) as measured by a Koivuranta score (K score) of 2 or more.

Pre-assignment details

36 participants were withdrawn prior to assignment into a treatment arm: 8 participants voluntarily withdrew prior to surgery date, 2 did not meet inclusion criteria, 6 had exclusion criteria, 3 withdrawn when study was closed to enrollment, 17 were withdrawn due to cancellation or re-scheduled surgery incompatible with study schedules.

Participants by arm

ArmCount
Arm 1: Dronabinol
dronabinol Dronabinol: Dronabinol (5mg) will be administered po 20-60 min pre-operatively.
64
Arm 2: Ondansetron
ondansetron Ondansetron: Ondansetron (4mg) will be administered iv intraoperatively in those patients not receiving Dronabinol.
57
Total121

Baseline characteristics

CharacteristicArm 1: DronabinolArm 2: OndansetronTotal
Age, Continuous57.8 years
STANDARD_DEVIATION 12.5
57.6 years
STANDARD_DEVIATION 13.2
57.7 years
STANDARD_DEVIATION 12.7
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
6 Participants8 Participants14 Participants
Race (NIH/OMB)
More than one race
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
58 Participants48 Participants106 Participants
Risk scores for PONV
K score=2
44 participants35 participants79 participants
Risk scores for PONV
K score >2
20 participants22 participants42 participants
Sex: Female, Male
Female
5 Participants2 Participants7 Participants
Sex: Female, Male
Male
59 Participants55 Participants114 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
2 / 926 / 88
serious
Total, serious adverse events
13 / 9210 / 88

Outcome results

Primary

Incidence of Postoperative Nausea and Vomiting

The incidence of postoperative nausea (PON) and postoperative vomiting (POV) was assessed during Post-operative Care Unit (PACU) stay.

Time frame: Post-operative Care Unit (PACU) length of stay on day of surgery (time from end of surgery to transfer to discharge unit or other hospital unit)

Population: Per protocol

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolIncidence of Postoperative Nausea and VomitingIncidence PACU PON34.4 percentage of participants
Arm 1:DronabinolIncidence of Postoperative Nausea and VomitingIncidence PACU POV12.5 percentage of participants
Arm 2:OndansetronIncidence of Postoperative Nausea and VomitingIncidence PACU PON29.8 percentage of participants
Arm 2:OndansetronIncidence of Postoperative Nausea and VomitingIncidence PACU POV7 percentage of participants
Comparison: The incidence of PON per arm will be determined and expressed as a percentage of the total patients per arm. Treatment efficacy will be measured as the percentage-point decrease in PON in the treatment arm (Marinol) compared to the standard therapy arm (ondansetron). Null hypothesis: Marinol treatment is not superior to ondansetron treatment. We will test the statistical significance with Fisher's Exact test at a significance level of 0.05p-value: >0.7690% CI: [-9.5, 18.6]Fisher Exact
Primary

Maximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) Scale

VAS Scale: 0=no nausea, 1-3=mild nausea, 4-6= moderate nausea, 7-9= severe nausea, 10=extreme nausea usually accompanied with vomiting. VAS nausea score were obtained every 30 min from entry into post-operative care unit (PACU) for first 2 hrs. and then hourly until time of transfer out of PACU.

Time frame: Post-operative Care Unit (PACU) stay from end of surgery to transfer to ambulatory unit

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleMild Nausea (VAS score=1-3)15.6 percentage of participants
Arm 1:DronabinolMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleSevere nausea (VAS score=7-9)7.8 percentage of participants
Arm 1:DronabinolMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleModerate Nausea (VAS score =4-6)7.8 percentage of participants
Arm 1:DronabinolMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleExtreme nausea (VAS score=10)9.4 percentage of participants
Arm 1:DronabinolMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleNo nausea (VAS score=0)59.4 percentage of participants
Arm 2:OndansetronMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleExtreme nausea (VAS score=10)8.8 percentage of participants
Arm 2:OndansetronMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleNo nausea (VAS score=0)70.2 percentage of participants
Arm 2:OndansetronMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleMild Nausea (VAS score=1-3)12.3 percentage of participants
Arm 2:OndansetronMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleModerate Nausea (VAS score =4-6)1.8 percentage of participants
Arm 2:OndansetronMaximum Reported Post-Operative Nausea Scores on Visual Analog Scale (VAS) ScaleSevere nausea (VAS score=7-9)7.0 percentage of participants
p-value: >0.92Fisher Exact
Primary

Post-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery

Participants were queried for presence of postoperative nausea (PON) or postoperative vomiting (POV) during the 24-48 hr window post surgery.

Time frame: 24-48 hrs post surgery

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolPost-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery24-48hr PON incidence23.4 percentage of participants
Arm 1:DronabinolPost-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery24-48 hr POV incidence6.3 percentage of participants
Arm 2:OndansetronPost-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery24-48hr PON incidence22.8 percentage of participants
Arm 2:OndansetronPost-operative Nausea and Vomiting (PONV) Incidence 24-48 Hours Post Surgery24-48 hr POV incidence3.5 percentage of participants
p-value: >0.5590% CI: [-12.1, 13.3]Fisher Exact
Secondary

Patient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication

Percent of participants willing to pay extra money for preemptive medication for PONV for subsequent surgical procedures when queried at post-operative 24-48 hr. and at 2-6 wk. follow-up interviews.

Time frame: Post-operative follow-up interviews 24 hr to 6 weeks post surgery

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolPatient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication24-48 hr. post-op80 percent of participants
Arm 1:DronabinolPatient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication2-6 wk post-op73 percent of participants
Arm 2:OndansetronPatient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication24-48 hr. post-op70 percent of participants
Arm 2:OndansetronPatient Satisfaction 2: Willingness to Pay Extra Money for Post-Operative Nausea and Vomiting (PONV) Preventive Medication2-6 wk post-op68 percent of participants
Comparison: Comparison of both group responses at 24-48 hours.p-value: >0.29FREQ procedure
Comparison: Comparisons of both arms at 2-6 weeks.p-value: >0.55FREQ Procedure
Secondary

Patient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting

Percent of participants who responded that they would be willing to take preemptive medication for nausea and vomiting for subsequent surgeries when queried during post-operative follow-up interviews at 24-48 hrs or 2-6 weeks.

Time frame: Post operative follow up interviews 24 hrs to 6 wks

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolPatient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting24-48 hr post-operative interview92 percent of participants
Arm 1:DronabinolPatient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting2-6 week post-operative interview87 percent of participants
Arm 2:OndansetronPatient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting24-48 hr post-operative interview89 percent of participants
Arm 2:OndansetronPatient Satisfaction: Willingness to Take Pre-operative Medication for Post-operative Nausea and/or Vomiting2-6 week post-operative interview75 percent of participants
Comparison: Comparisons at 24-48 hr post-surgery. Null hypothesis: dronabinol is not superior to ondansetron in patient satisfaction.p-value: >0.75FREQ Procedure
Comparison: Comparisons of both arms at 2-6 weeks; null hypothesis: dronabinol is not superior to ondansetron in patient satisfactionp-value: >0.1FREQ procedure
Secondary

Post-operative Antiemetic Use

Percentage of participants requiring post-operative anti-emetic medications.. Anti-emetic medication need was assessed during a) post-operative care unit (PACU) stay and b)during the first 48 hrs. following discharge from PACU to home or if applicable to in-patient unit.

Time frame: End of surgery to 48 hr post surgery

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolPost-operative Antiemetic UseMedication need during PACU stay25 percentage of participants
Arm 1:DronabinolPost-operative Antiemetic UseMedication need for first 48 hrs after discharge t3 percentage of participants
Arm 2:OndansetronPost-operative Antiemetic UseMedication need during PACU stay17 percentage of participants
Arm 2:OndansetronPost-operative Antiemetic UseMedication need for first 48 hrs after discharge t4 percentage of participants
p-value: >0.37Fisher Exact
Secondary

Post-Operative Care Unit Length of Stay (Min)

Length of time in PACU (minutes) measured from end of surgery to time of transfer to ambulatory care prior to home discharge or time to hospital admission if applicable.

Time frame: Day of surgery (time from end of surgery to transfer to ambulatory pre-discharge unit or other unit)

ArmMeasureValue (MEDIAN)
Arm 1:DronabinolPost-Operative Care Unit Length of Stay (Min)99.5 minutes
Arm 2:OndansetronPost-Operative Care Unit Length of Stay (Min)97.0 minutes
p-value: =0.981Wilcoxon Rank-Sum test
Secondary

Post-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal Procedure

Number of all-cause hospital admissions on day of elective out-patient surgery .

Time frame: Post-operative Day of Surgery (DOS)

ArmMeasureGroupValue (NUMBER)
Arm 1:DronabinolPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission- urinary retension4 participants
Arm 1:DronabinolPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission- low SpO21 participants
Arm 1:DronabinolPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission-pain management1 participants
Arm 1:DronabinolPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission -intractable nausea/vomitting0 participants
Arm 1:DronabinolPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission-observation3 participants
Arm 2:OndansetronPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission -intractable nausea/vomitting0 participants
Arm 2:OndansetronPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission-observation3 participants
Arm 2:OndansetronPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission- urinary retension3 participants
Arm 2:OndansetronPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission-pain management1 participants
Arm 2:OndansetronPost-Surgery Hospital Admissions (All Cause) After Out-patient Abdominal ProcedureDOS admission- low SpO20 participants
p-value: >0.9Fisher Exact

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026