Olanzapine for Nausea After Surgery

Olanzapine for the Treatment of Post-Discharge Nausea and Vomiting After Ambulatory Surgery

Ambulatory surgery is occurring with rapidly increasing frequency as surgical and anesthetic techniques have improved and pressure to reduce health-care costs has increased. While there are many benefits to recovering from surgery within the home, a significant disadvantage is the lack of rapid access to a healthcare provider when postoperative complications occur. Postoperative nausea and vomiting (PONV) are common after surgery and anesthesia, and recent studies have demonstrated a high incidence of post-discharge nausea and vomiting (PDNV) after ambulatory surgery, particularly in high-risk groups (female gender, age less than 50 years, history of PONV, opioid administration in the post-anesthesia care unit (PACU), and nausea in the PACU). Current practices known to reduce the risk of postoperative nausea and vomiting in the PACU, such as the avoidance of volatile anesthetics and the use of intraoperative ondansetron and steroids, have little effect on the risk of delayed PDNV. Novel strategies to prevent PDNV are needed. Orally administered olanzapine, which has been shown to decrease the incidence of chemotherapy-induced nausea and vomiting, demonstrates promise as a novel strategy for preventing PDNV. It has a long half-life, allowing for a single dose to be administered preoperatively. This study will evaluate whether there is a difference in the incidence and severity of PDNV between patients who receive oral olanzapine versus placebo prior to general anesthesia for ambulatory surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Olanzapine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinaï

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Adults age ≥ 18 and ≤ 50 years old
• Patient scheduled to undergo ambulatory surgery under general anesthesia
• Willing and able to provide informed consent

Exclusion Criteria:

• Unable to swallow pills
• Current use of typical or atypical anti-psychotic medications
• History of allergy to olanzapine
• Pregnancy/Lactation (subjects of child-bearing potential will have a urine pregnancy test performed the day of surgery)
• History of QTc > 450ms or torsades de pointes
• Current use of antihypertensive medication
• Diabetes Mellitus

• Clinically significant cardiovascular disease defined as follows:

  1. Myocardial infarction or unstable angina within 6 months prior to the day of planned surgery.
  2. History of serious ventricular arrhythmia (i.e.: ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled on anti-arrhythmic medication.
  3. New York Heart Association (NYHA) Class II or higher congestive heart failure.
• Postural hypotension or vasovagal syncope within 6 months of planned surgery.
• Hypotension on day of surgery, defined as a systolic blood pressure < 90mm Hg or a diastolic pressure < 60mm Hg.
• Seizure disorder
• Clinically active prolactinoma
• Hepatic disease
• Poorly controlled diabetes
• Pre-operative blood glucose > 250 mg/dL
• Narrow angle glaucoma
• Parkinson's disease
• Lewy body dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo by mouth prior to anesthetic induction
Experimental: Olanzapine; 10mg pill	Drug: Olanzapine; 10mg of olanzapine by mouth prior to anesthetic induction; Other Names: Zyprexa; Zyprexa Zydis; 132539-06-1; Olansek; Symbyax2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Nausea and/or Vomiting	Number of participants with post-discharge nausea and/or vomiting	in 24 hours after discharge
Number of Participants With Severe Nausea	Number of participants with severe postdischarge nausea, defined as numerical rating scale score greater than 3. (11-point numerical rating scale from 0-10, higher score indicating worse nausea)	in 24 hours after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Postdischarge Vomiting	Number of participants with post discharge vomiting	in 24 hours after discharge
Number of Participants With PONV	Number of participants with postoperative nausea and/or vomiting (PONV) in first 24 hours	first 24 hours post-op
Number of Participants With Severe PONV	Number of participants with severe PONV in first 24 hours after post-op.defined as numerical rating scale score greater than 3. (11-point numerical rating scale from 0-10, higher score indicating worse nausea)	first 24 hours post-op

Collaborators and Investigators

• Sponsor: Jaime B Hyman
• Investigators: Principal Investigator: Jaime B Hyman, MD, Icahn School of Medicine at Mount Sinaï

Publications and helpful links

General Publications

• Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, Allard M, Turan A, Windle P, Odom-Forren J, Hooper VD, Radke OC, Ruiz J, Kovac A. Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology. 2012 Sep;117(3):475-86. doi: 10.1097/ALN.0b013e318267ef31.
• Hyman JB, Park C, Lin HM, Cole B, Rosen L, Fenske SS, Barr Grzesh RL, Blank SV, Polsky SB, Hartnett M, Taub PJ, Palvia V, DeMaria S Jr, Ascher-Walsh C. Olanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial. Anesthesiology. 2020 Jun;132(6):1419-1428. doi: 10.1097/ALN.0000000000003286. Erratum In: Anesthesiology. 2020 Jun 5;:

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): September 5, 2019

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: April 26, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Nausea; 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; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: GCO 15-1297

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No