Pre-operative Olanzapine as Prophylactic Antiemetic in Oncologic Patients

• ClinicalTrials.gov Identifier: NCT03631004
• Recruitment Status: Completed
• First Posted: August 15, 2018
• Last Update Posted: January 13, 2022
• Sponsor: Instituto do Cancer do Estado de São Paulo
• Information provided by (Responsible Party): Instituto do Cancer do Estado de São Paulo

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Nausea; Postoperative Nausea and Vomiting	Drug: Olanzapine	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Pre-operative Olanzapine as Prophylactic Antiemetic in Oncologic Patients
• Actual Study Start Date: October 1, 2018
• Actual Primary Completion Date: February 10, 2021
• Actual Study Completion Date: February 10, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. incidence of postoperative nausea and vomiting [ Time Frame: 0-24 hours ]
   nausea and vomiting/ retching (dichotomous variable)

Secondary Outcome Measures :

1. incidence of side effects [ Time Frame: 0-6 hours ]
   side effects
2. incidence of side effects [ Time Frame: 0-24 hours ]
   side effects
3. incidence of side effects [ Time Frame: 24-48 hours ]
   side effects
4. incidence of postoperative nausea and vomiting [ Time Frame: 0-6 hours ]
   nausea and vomiting/ retching (dichotomous variable)
5. incidence of postoperative nausea and vomiting [ Time Frame: 24-48 hours ]
   nausea and vomiting/ retching (dichotomous variable)
6. incidence of postoperative nausea [ Time Frame: 0-6 hours ]
   nausea and vomiting/ retching (dichotomous variable)
7. incidence of postoperative nausea [ Time Frame: 0-24 hours ]
   nausea and vomiting/ retching (dichotomous variable)
8. incidence of postoperative nausea [ Time Frame: 24-48 hours ]
   nausea and vomiting/ retching (dichotomous variable)
9. incidence of postoperative vomiting/retching [ Time Frame: 0-6 hours ]
   vomiting/ retching (dichotomous variable)
10. incidence of postoperative vomiting/retching [ Time Frame: 0-24 hours ]
    vomiting/ retching (dichotomous variable)
11. incidence of postoperative vomiting/retching [ Time Frame: 24-48 hours ]
    vomiting/ retching (dichotomous variable)
12. incidence of severe PONV [ Time Frame: 0-6 hours ]
    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.
13. incidence of severe PONV [ Time Frame: 0-24 hours ]
    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.
14. incidence of severe PONV [ Time Frame: 24-48 hours ]
    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.
15. incidence of nausea severity [ Time Frame: 0-6 hours ]
    mild, moderate, or severe
16. incidence of nausea severity [ Time Frame: 0-24 hours ]
    mild, moderate, or severe
17. incidence of nausea severity [ Time Frame: 24-48 hours ]
    mild, moderate, or severe

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Brazil

Cancer Institute of the State of Sao Paulo - ICESP

Sao Paulo, São Paulo, Brazil, 01403010

Sponsors and Collaborators

Instituto do Cancer do Estado de São Paulo

Investigators

• Study Director: Roger Chammas; Instituto do Cancer do Estado de São Paulo

More Information

• Responsible Party: Instituto do Cancer do Estado de São Paulo
• ClinicalTrials.gov Identifier: NCT03631004
• Other Study ID Numbers: 1287/18
• First Posted: August 15, 2018
• Last Update Posted: January 13, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Instituto do Cancer do Estado de São Paulo:

nausea and vomiting

Additional relevant MeSH terms:

Nausea; Vomiting; Postoperative Nausea and Vomiting; Signs and Symptoms, Digestive; Postoperative Complications; Pathologic Processes; Olanzapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents