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Trial registered on ANZCTR


Registration number
ACTRN12619000744156
Ethics application status
Approved
Date submitted
8/05/2019
Date registered
20/05/2019
Date last updated
20/09/2022
Date data sharing statement initially provided
20/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Management of nausea in cancer patients – Nausea study 4 pilot
Scientific title
A randomised, controlled study of oral olanzapine versus oral haloperidol in patients with cancer and nausea not related to anticancer therapy (Nausea study 4 pilot)
Secondary ID [1] 297579 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
NS4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nausea
 312054 0
Advanced Cancer 312055 0
Condition category
Condition code
Cancer 310618 310618 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a 2 arm, randomised controlled study where participants with advanced cancer experiencing nausea (not related to anticancer therapy) will be randomised to receive either oral olanzapine or haloperidol.

Arm 1: Olanzapine (also known as Zyprexa®)
Dose level 1: 2.5mg tablet orally once daily
Dose level 2: 2.5mg tablet orally twice daily
Treatment period: 3 x 24hours study period

Arm 2: Haloperidol (also known as Serenace®)
Dose level 1: 0.5mg tablet orally once daily
Dose level 2: 0.5mg tablet orally twice daily
Treatment period: 3 x 24hours study period

The dose of trial medications can be increased once, to dose level 2, at 24 or 48 hours. The decision to increase dose level is primarily a clinical decision based on degree of response and toxicity.

The pharmacy will maintain accountability records, in addition to the study allocation records.

Metoclopramide 10mg (as required) 6-hourly orally or parenterally (subcutaneous or intravenous) to a maximum dose of 60mg/24 hours. Assessments for need for rescue doses will be according to normal ward (or community) practice. Rescue doses should be freely available and given regularly in those participants not responding to the medications.
Domperidone 10-20mg 6-hourly orally is an acceptable alternative for those participants unable to tolerate metoclopramide. Domperidone cannot be given parenterally. The number of rescue doses given each 24 hours will be recorded and used to determine response status.
No other antiemetic, regular and as required, is not allowed during the 3-day trial period. Any participants given non-trial antiemetics during the trial period will be withdrawn from study.
Intervention code [1] 313976 0
Treatment: Drugs
Comparator / control treatment
Haloperidol is being used as the standard single agent treatment for this study.
Control group
Active

Outcomes
Primary outcome [1] 319480 0
The effectiveness of oral olanzapine versus oral haloperidol in improving the management of nausea in patients with cancer and nausea not related to anticancer therapy. A response would be a greater than or equal to 2 point improvement from baseline for average nausea over the preceding 24 hours on an 11 point nausea NRS.
Timepoint [1] 319480 0
Eligibility, baseline, Day 1, 2 and 3 of intervention and at follow up for week 1, 2, 3 and 4.
Secondary outcome [1] 368350 0
The effectiveness at each dose level of the medications which will be assessed using the nausea NRS at each day of the intervention.
Timepoint [1] 368350 0
Eligibility, baseline, Day 1, 2 and 3 of intervention and at follow up for week 1, 2, 3 and 4.
Secondary outcome [2] 368351 0
The complete control of nausea in each arm which will be defined as at least a two-point improvement from baseline and a score <3 for average nausea over the preceding 24 hours, measured at 72 hours from time of first study drug administration using an 11-point nausea NRS.
Timepoint [2] 368351 0
Baseline, Day 1, 2 and 3 of intervention and at follow up for week 1, 2, 3 and 4.
Secondary outcome [3] 368352 0
The amount of rescue metoclopramide therapy used in each arm which will be measured by conducting a rescue dose review. This involves a medical chart review or daily phone call to the patient.
Timepoint [3] 368352 0
Baseline, Day 1, 2 and 3 of intervention, at 72 hours (or exit) from the study and at follow up for week 1, 2, 3 and 4.
Secondary outcome [4] 368353 0
The number of episodes of vomiting within each 24 hr study period for patients on either arm. This will be assessed by way of medical record and patient recall.
Timepoint [4] 368353 0
Eligibility, baseline, Day 1, 2 and 3 of intervention and at follow up for week 1, 2, 3 and 4.
Secondary outcome [5] 368354 0
The side effect profile of olanzapine and haloperidol which will be reviewed using criteria established by the National Cancer Institute Adverse Event Criteria (V4.0). Olanzapine: Common side effects: - somnolence - weight gain - asthenia - arthralgia - hypotension - constipation - peripheral oedema - dry mouth - dizziness Less common: - increased LFTs, BGL, HbA1c, gamma glutamyl transferase, uric acid, lipids - hyperprolactinaemia - hallucinations - parkinsonian symptoms - tardive dyskinesia - body temperature regulation disruption - dysphagia - falls - abnormal gait - TIA - Stroke Rare: - NMS - SCAR (disc) - Jaundice - Pancreatitis - Hypersensitivity - VTE - Rhabdomyolysis - sudden cardiac death - QT prolongation - ventricular arrhythmia - cardiac arrest Haloperidol: Common side effects: - drowsiness - fatigue - hypotension (new onset dizziness, especially on standing) - dizziness Less common: - disorientation - confusion - constipation - dry mouth - blurred vision - hypertension - movement disorders e.g. tremor, slowness as in Parkinson’s disease (high doses only) - QT interval prolongation (if serial ECGs are taken) Rare: - bone marrow failure (bleeding or bruising) - hypersensitivity to light - allergic reactions (skin rash, swelling, itching, welts) - jaundice (yellow skin change) - abnormal heart rhythm (palpitations)urinary retention
Timepoint [5] 368354 0
Baseline, Day 1, 2 and 3 of intervention, at 72 hours (or exit) from the study and at follow up for week 1, 2, 3 and 4.
Secondary outcome [6] 368355 0
An economic analysis of the management of nausea in cancer patients. Specifically, the cost of medications, days in hospital within each arm and the cost of medical records will all be assessed.
Timepoint [6] 368355 0
Baseline, Day 1, 2 and 3 of intervention, at 72 hours (or exit) from the study and at follow up for week 1, 2, 3 and 4.

Eligibility
Key inclusion criteria
Patients who:
- are 18 years or over
- have a clinical diagnosis of cancer
- have nausea with an average score over the last 24 hours of greater than or equal to 3 on an 11 point numerical rating scale (NRS) anchored at 0 (no nausea) and 10 (worst possible nausea)
- are able to tolerate oral medications
- are able to comply with all trial requirements
- are able to provide fully informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who:
-have nausea related to the treatment of cancer (i.e. surgery, chemotherapy, radiotherapy) within 5 days of anticancer therapy
-have nausea for which a specific antiemetic is indicated and randomisation to study medications alone would not be appropriate (dexamethasone for acutely raised ICP, 5HT3 antagonists for chemotherapy induced nausea/vomiting)
-are to undergo a procedure or intervention with the potential to affect nausea during the 3 day study period (e.g. chemotherapy or radiotherapy to a site likely to cause nausea)
-have received ondansetron, olanzapine or haloperidol at doses equivalent to dose level 1 per day within the previous 48 hours
-have had uncontrolled nausea despite treatment with ondansetron, olanzapine or haloperidol at study doses within the previous 2 weeks
-if on corticosteroids, the dose has changed within 48 hours prior to study or is likely to change during the 3 day study period
-have a definite contraindication to haloperidol (Parkinson’s disease, movement disorders, severe hepatic impairment*)
-documented congenital or acquired (drug induced#) QTc prolongation (QTc>440sec in men and >0.46sec in women, calculated manually as per Bazett’s formula^) or factors that exacerbate QT prolongation i.e. untreated hypokalaemia, hypothyroidism or bradyarrythmias
-uncontrolled epilepsy or glaucoma
-concurrent treatment with monoamine oxidase inhibitors
-have had a previous adverse reaction to the study medications
-are pregnant or breastfeeding
-have participated in a trial of a new clinical entity within the last 28 days

* this applies to AST, ALT or bilirubin but not to ALP or GGT
# see appendix for drugs with the potential to prolong QT
^ QTc=QT interval/square root of the RR interval (in sec)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation schedules will be developed for each site using random number tables, generated at an independent centre (central registry). Treatment for each patient will be allocated according to a block randomisation schedule held by the central registry in a 1:1 ratio.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Allowing 20% for attrition, and with response rates of 50% for olanzapine and haloperidol, it is anticipated that 24 participants (12 per treatment arm) should be randomized to achieve a sample size of 10 participants per arm.

The efficacy of olanzapine versus haloperidol will be tested by comparing the response to each drug after 72 hours, relative to baseline. Descriptive analyses and frequency distributions will be generated from participants’ demographic and clinical characteristics. Chi-square tests and logistic regression will be used to test for differences in response rates.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/06/2019
Actual
8/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13427 0
Mater Private Hospital - South Brisbane
Recruitment postcode(s) [1] 26032 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 302127 0
University
Name [1] 302127 0
The University of Technology Sydney
Country [1] 302127 0
Australia
Primary sponsor type
University
Name
The University of Technology Sydney
Address
15 Broadway, Ultimo NSW 2007
Country
Australia
Secondary sponsor category [1] 302131 0
None
Name [1] 302131 0
Address [1] 302131 0
Country [1] 302131 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302808 0
Mater Human Research Ethics Committee and Research Governance
Ethics committee address [1] 302808 0
Ethics committee country [1] 302808 0
Australia
Date submitted for ethics approval [1] 302808 0
01/03/2019
Approval date [1] 302808 0
10/04/2019
Ethics approval number [1] 302808 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91470 0
A/Prof Philip Good
Address 91470 0
Mater Misericordiae Ltd, Raymond Tce
South Brisbane, QLD, 4101
Country 91470 0
Australia
Phone 91470 0
+61 31635689
Fax 91470 0
Email 91470 0
phillip.good@mater.org.au
Contact person for public queries
Name 91471 0
Philip Good
Address 91471 0
Mater Misericordiae Ltd, Raymond Tce
South Brisbane, QLD, 4101
Country 91471 0
Australia
Phone 91471 0
+61 31635689
Fax 91471 0
Email 91471 0
phillip.good@mater.org.au
Contact person for scientific queries
Name 91472 0
Philip Good
Address 91472 0
Mater Misericordiae Ltd, Raymond Tce
South Brisbane, QLD, 4101
Country 91472 0
Australia
Phone 91472 0
+61 31635689
Fax 91472 0
Email 91472 0
phillip.good@mater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.