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Trial registered on ANZCTR


Registration number
ACTRN12615000177550
Ethics application status
Approved
Date submitted
2/02/2015
Date registered
23/02/2015
Date last updated
11/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study for participants with cancer who experience ongoing nausea, not related to their treatment, despite taking standard and usual medications, that studies the effectiveness of oral methotrimeprazine versus oral haloperidol.
Scientific title
A randomised, controlled, double blind study of oral methotrimeprazine versus oral haloperidol in patients with cancer and nausea not related to anticancer therapy (Nausea study 3), to compare the effectiveness of oral methotrimeprazine versus oral haloperidol in improving the management of nausea in patients with cancer and nausea not related to anticancer therapy.
Secondary ID [1] 286085 0
NIL
Universal Trial Number (UTN)
N/A
Trial acronym
Nausea study 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with cancer and nausea not related to anticancer treatment. 294084 0
Condition category
Condition code
Cancer 294392 294392 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomized to receive either blinded encapsulated oral methotrimeprazine (6.25mg ) or oral haloperidol (1.5mg ) both given once daily (od), for three intervention days. All other regular antiemetics will be discontinued. Metoclopramide 10mg every 6 hours subcutaneous or oral (max dose 30mg/24hrs taken at any time during the intervention as long as it is 4 hours apart) will be available as a rescue antiemetic as well as Domperidone 10-20mg up to four times per day, per oral as an alternative to metoclopramide (taken when needed during intervention period). In the absence of response at 24 hours or 48 hours, the dose of the study drug can be increased to twice daily (total daily dose 12.5mg methotrimeprazine or 3mg haloperidol). All study drug/bottles to be returned at completion of study or study withdrawal/exit.
Intervention code [1] 291078 0
Treatment: Drugs
Comparator / control treatment
Haloperidol is the standard treatment by which the methotrimeprazine will be compared to.
Control group
Active

Outcomes
Primary outcome [1] 294184 0
Response to treatment, at 72 hours from time of first study drug administration, defined as more than or equal to a 2 point improvement from baseline for average nausea over the preceding 24 hours on an 11 point nausea NRS
Timepoint [1] 294184 0
Response to treatment at 72 hours
Secondary outcome [1] 312718 0
Complete response defined as at least a two-point improvement from baseline and a score less than 3 for average nausea over the preceding 24 hours, using an 11-point (0-10) Numerical Rating Scale.
Timepoint [1] 312718 0
measured at 72 hours from time of first study drug administration
Secondary outcome [2] 312719 0
Response defined as equal too or more than 2 point improvement from the baseline average nausea score over the preceeding 24hours on an 11 point (0-10) Numerical Rating Scale.
Timepoint [2] 312719 0
Assessed at 24 hours, 48 hours post first study drug administration.
Secondary outcome [3] 312720 0
Best nausea score over the preceding 24 hours, using an 11-point (0-10) numeric rating scale
Timepoint [3] 312720 0
measured at 72 hours from time of first study drug administration
Secondary outcome [4] 312721 0
The number of rescue antiemetic doses delivered as per the inpatient medication chart or the participants diary of medications as an outpatient.
Timepoint [4] 312721 0
+24hr, +48hrs, +72hrs from first study drug administration.
Secondary outcome [5] 312722 0
Toxicity, assessed by adverse event list.
Timepoint [5] 312722 0
+24hrs, +48hrs, +72hrs since first study drug and then weekly for 4 weeks post intervention.
Secondary outcome [6] 312724 0
The number of episodes of vomiting experienced (episode of vomiting considered a 20 minute period - dry retching not included) documented on the Case Report forms for the 24 hour period after study drug as per the participant or nursing staff if an inpatient.
Timepoint [6] 312724 0
Assessed at 24 hours, 48 hours, and 72 hours post first study drug administration and then weekly for four weeks.
Secondary outcome [7] 312887 0
complete response defined as at least a two-point improvement from baseline and a score less than 3 for average nausea over the preceding 24 hours, using an 11-point (0-10) Numerical Rating Scale.
Timepoint [7] 312887 0
Assessed at 24 hours, 48 hours post first study drug administration.

Eligibility
Key inclusion criteria
1. are 18 years or over
2. have a clinical diagnosis of cancer
3. 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)
4. are able to tolerate oral medications
5. are able to comply with all trial requirements
6. are able to provide fully informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. have nausea related to the treatment of cancer (i.e. surgery, chemotherapy, radiotherapy) within 5 days of anticancer therapy
2. 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)
3. are to undergo a procedure or intervention with the potential to affect nausea during the 3 day study period (eg chemotherapy or radiotherapy to a site likely to cause nausea)
4. have received methotrimeprazine or haloperidol at doses equivalent to dose level 1 per day within the previous 48 hours
5. have had uncontrolled nausea despite treatment with methotrimeprazine or haloperidol at study doses within the previous 2 weeks
6. if on corticosteroids, the dose has changed within 48 hours prior to study or is likely to change during the 3 day study period
7. have a definite contraindication to methotrimeprazine (severe hepatic impairment (LFTs above 5 x upper limit of normal, symptomatic postural hypotension, phenothiazine hypersensitivity, concurrent treatment with MAOIs, severe renal disease (eGFR less than 30), severe myocardial disease (clinician assessment))
8. have a definite contraindication to haloperidol (Parkinson’s disease, movement disorders, severe hepatic impairment)
9. documented congenital or acquired (drug induced#) QTc prolongation (QTc greater than 440sec in men and greater than 0.46sec in women, calculated manually as per Bazett’s formula) or factors that exacerbate QT prolongation ie untreated hypokalaemia, hypothyroidism or bradyarrythmias
10. uncontrolled epilepsy or glaucoma
11. concurrent treatment with monoamine oxidase inhibitors
12. have had a previous adverse reaction to the study medications
13. are pregnant or breastfeeding
14. have participated in a trial of a new clinical entity within the last 28 days

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)
The clinical trials pharmacy is responsible for the allocation of treatment arms.
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. Block randomisation within centre will ensure even allocation to each code in each site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Our assumptions for sample size are based on others’ research and some of our own work. Allowing 20% for attrition, and with response rates of 85% for methotrimeprazine compared to 60% for haloperidol, it is anticipated that 126 participants (63 per treatment arm) should be randomized to achieve a sample size of 50 participants per arm, assuming 80 % power, a simple random sampling scheme and a Type 1 error of 5% (two-tailed).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 3381 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 3382 0
Mater Private Hospital - South Brisbane
Recruitment hospital [3] 3383 0
Noarlunga Private Hospital - Noarlunga Centre
Recruitment hospital [4] 3384 0
Repatriation Hospital - Daw Park
Recruitment hospital [5] 3385 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 3386 0
Barwon Health - McKellar Centre campus - North Geelong
Recruitment hospital [7] 3387 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [8] 3388 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [9] 3389 0
St Vincent's Hospital Brisbane - Kangaroo Point
Recruitment hospital [10] 3390 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [11] 4331 0
Flinders Private Hospital - Bedford Park
Recruitment hospital [12] 5324 0
Greenwich Hospital - Greenwich
Recruitment hospital [13] 5995 0
Caritas Christi Hospice - Kew
Recruitment postcode(s) [1] 9166 0
4101 - South Brisbane
Recruitment postcode(s) [2] 9168 0
4169 - Kangaroo Point
Recruitment postcode(s) [3] 9169 0
5168 - Noarlunga Centre
Recruitment postcode(s) [4] 9170 0
5041 - Daw Park
Recruitment postcode(s) [5] 9171 0
5042 - Bedford Park
Recruitment postcode(s) [6] 9173 0
3220 - Geelong
Recruitment postcode(s) [7] 9174 0
3215 - North Geelong
Recruitment postcode(s) [8] 9175 0
3065 - Fitzroy
Recruitment postcode(s) [9] 9176 0
2010 - Darlinghurst
Recruitment postcode(s) [10] 12786 0
2065 - Greenwich
Recruitment postcode(s) [11] 13420 0
3101 - Kew

Funding & Sponsors
Funding source category [1] 290673 0
Government body
Name [1] 290673 0
NHMRC Research Grant
Address [1] 290673 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 290673 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Palliative Care Clinical Studies Collaborative (PaCCSC)
Address
Flinders University
School of Medicine
Department of Palliative and Supportive Services
C/- Daw House Hospice
700 Goodwood Road
Daw Park SA 5041
AUSTRALIA

Country
Australia
Secondary sponsor category [1] 289366 0
University
Name [1] 289366 0
The Queensland University of Technology
Address [1] 289366 0
GPO Box 2434
Brisbane, QLD 4001
Country [1] 289366 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292303 0
The Royal Brisbane and Women's Hospital HREC
Ethics committee address [1] 292303 0
Royal Brisbane and Women's Hospital
Level 7 Block 7
Butterfield Street, Herston, QLD
Australia, 4029
Ethics committee country [1] 292303 0
Australia
Date submitted for ethics approval [1] 292303 0
10/11/2014
Approval date [1] 292303 0
01/12/2014
Ethics approval number [1] 292303 0
HREC/14/QRBW/466

Summary
Brief summary
This study aims to find out if a drug called Nozinan (methotrimeprazine) works better in treating nausea that is cancer related than the standard drug Haloperidol. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have cancer related nausea to a certain level of nausea that is not from cancer treatment. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive Nozinan tablets once daily (up to twice daily if necessary) for 3 days, whilst participants in the other group will receive Haloperidol tablets once daily (up to twice daily if necessary) for 3 days. Neither you nor the research team or Doctor will know which drug you will get. You will also have access to two other 'rescue' nausea medications as a back-up for your nausea. You will be required to fill out questionnaires related to your nausea/symptoms before the study drug starts, every 24 hrs after the drug is taken, when the study drug finishes, and for four weekly follow-ups. You can be an in-patient or an outpatient to complete this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54550 0
Prof Janet R Hardy
Address 54550 0
Director of Palliative Care Mater Misericordiae Ltd Raymond Terrace South Brisbane QLD 4101
Country 54550 0
Australia
Phone 54550 0
+617 3163 2775
Fax 54550 0
+617 3163 2701
Email 54550 0
janet.hardy@mater.org.au
Contact person for public queries
Name 54551 0
Miss Georgie Cupples
Address 54551 0
Mater Misericordiae Ltd Raymond Terrace South Brisbane QLD 4101
Country 54551 0
Australia
Phone 54551 0
+617 3163 3884
Fax 54551 0
+617 3163 1588
Email 54551 0
Georgie.Cupples@mater.org.au
Contact person for scientific queries
Name 54552 0
Prof Janet R Hardy
Address 54552 0
Director of Palliative Care Mater Misericordiae Ltd Raymond Terrace South Brisbane QLD 4101
Country 54552 0
Australia
Phone 54552 0
+617 3163 2775
Fax 54552 0
+617 3163 2701
Email 54552 0
janet.hardy@mater.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary