Pre-operative Olanzapine as Prophylactic Antiemetic in Oncologic Patients

Olanzapine has been used as prophylactic antiemetic for chemotherapy induced nausea and vomiting.

The project aims to evaluate the efficacy of olanzapine in combination with ondansetron and dexamethasone in patients at high risk of postoperative nausea and vomiting, with previous history of nausea and vomiting induced by prior chemotherapy, submitted to medium and large surgery.

Study Overview

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

Detailed Description

Double blinded randomized clinical trial. Fifty patients will be selected for each group. Group A will receive 10mg olanzapine in the preoperative and group B will receive placebo in the preoperative period. Both groups will receive intravenous general anesthesia combined with epidural. All patients will receive epidural PCA.

The primary outcome of this study is the incidence of post-operative nausea and vomiting. The power of analysis was based on the following parameters: type error I (α = 0.05), error II (β = 0.8), 95% confidence interval and hypothesis test two-tailed. Thus, 42 patients are indicated per group to obtain reduction of the incidence of nausea and / or vomiting of the population risk from 60% to 30%. The population will be composed of 100 patients because it is assumed that percentage of loss of 10% per group.

The statistical analysis will be performed in program R version 3.5.1. The results obtained will be presented as mean + standard deviation for continuous data or absolute frequency for described data.

For quantitative variables, the Student's t-test will be used for with normal distribution or Mann-Whitney for non-distributed data normal.

For qualitative variables, the chi-square test will be used or Fisher's exact test. Significant difference is defined as p, 0.05.

Data will be collected and managed using REDCap data capture tools

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01403010
      • Cancer Institute of the State of Sao Paulo - ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients submitted to medium and large surgeries in the thoracic or abdominal region (mastectomies, breast plastic, hysterectomies, annexectomies, gynecological pelvic surgeries, colectomies, rettosigmoidectomies) under general anesthesia
• Patients aged between 18 and 60 years
• Patients considered to be at high risk for PONV according to the Apfel scale (Apfel 3 or 4)
• Patients with a history of chemotherapy-induced nausea and vomiting.

Exclusion criteria:

• Pregnancy or Lactation
• Current use of typical anti-psychotic medications or atypical
• History of allergy to olanzapine
• Myocardial infarction or unstable angina in the 6 months prior to the day of surgery planning
• History of severe ventricular arrhythmia (eg, VT or VF)
• Heart Failure Class II or greater second NYHA
• Postural hypotension or vasovagal syncope in the 6 months prior to the day of surgery planning
• Narrow angle glaucoma
• Parkinson's disease
• Dementia
• Inability to swallow medicines
• QT interval history greater than 450ms or torsades de pointes
• Patient does not want to participate in the study
• Videolaparoscopy surgery
• Contraindication for neuraxial block

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
Experimental: olanzapine tablets; PATIENT WILL TAKE OLANZAPINE 10 MG, 1 hour BEFORE SURGERY	Drug: Olanzapine; olanzapine 10 mg is given before surgery; Other Names: Treatment
Placebo Comparator: Starch tablets; PATIENT WILL TAKE PLACEBO 1 hour BEFORE SURGERY	Drug: Olanzapine; olanzapine 10 mg is given before surgery; Other Names: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of postoperative nausea and vomiting	nausea and vomiting/ retching (dichotomous variable)	0-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of side effects	side effects	0-6 hours
incidence of side effects	side effects	0-24 hours
incidence of side effects	side effects	24-48 hours
incidence of postoperative nausea and vomiting	nausea and vomiting/ retching (dichotomous variable)	0-6 hours
incidence of postoperative nausea and vomiting	nausea and vomiting/ retching (dichotomous variable)	24-48 hours
incidence of postoperative nausea	nausea and vomiting/ retching (dichotomous variable)	0-6 hours
incidence of postoperative nausea	nausea and vomiting/ retching (dichotomous variable)	0-24 hours
incidence of postoperative nausea	nausea and vomiting/ retching (dichotomous variable)	24-48 hours
incidence of postoperative vomiting/retching	vomiting/ retching (dichotomous variable)	0-6 hours
incidence of postoperative vomiting/retching	vomiting/ retching (dichotomous variable)	0-24 hours
incidence of postoperative vomiting/retching	vomiting/ retching (dichotomous variable)	24-48 hours
incidence of severe PONV	This scale consists of four questions. Each question generates a different score. For the first question, if the patient vomited or retched three or more times, the final score was 50. Otherwise, the highest score from question 1 or question 2 was multiplied by the scores of question 3 and question 4, yielding the final value. When the score was ≥ 50, the symptom was considered clinically important.	0-6 hours
incidence of severe PONV	This scale consists of four questions. Each question generates a different score. For the first question, if the patient vomited or retched three or more times, the final score was 50. Otherwise, the highest score from question 1 or question 2 was multiplied by the scores of question 3 and question 4, yielding the final value. When the score was ≥ 50, the symptom was considered clinically important.	0-24 hours
incidence of severe PONV	This scale consists of four questions. Each question generates a different score. For the first question, if the patient vomited or retched three or more times, the final score was 50. Otherwise, the highest score from question 1 or question 2 was multiplied by the scores of question 3 and question 4, yielding the final value. When the score was ≥ 50, the symptom was considered clinically important.	24-48 hours
incidence of nausea severity	mild, moderate, or severe	0-6 hours
incidence of nausea severity	mild, moderate, or severe	0-24 hours
incidence of nausea severity	mild, moderate, or severe	24-48 hours

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): February 10, 2021
• Study Completion (Actual): February 10, 2021

Study Registration Dates

• First Submitted: August 11, 2018
• First Submitted That Met QC Criteria: August 11, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: nausea and 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: 1287/18

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No