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.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000177550
• Date of registration: 23/02/2015
• Prospective Registration: Yes
• Primary sponsor: Palliative Care Clinical Studies Collaborative (PaCCSC)
• 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.
• Date of first enrolment: 26/03/2015
• Target sample size: 126
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12615000177550.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 3

Countries of recruitment

Australia

Contacts

• Name: Miss Georgie Cupples

• Name: Prof Janet R Hardy

Key inclusion & exclusion criteria

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

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


Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Any cancer

Patients with cancer and nausea not related to anticancer treatment. ;
Patients with cancer and nausea not related to anticancer treatment.

Intervention(s)

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.

Primary Outcome(s)

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 [Response to treatment at 72 hours]

Secondary Outcome(s)

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. [Assessed at 24 hours, 48 hours, and 72 hours post first study drug administration and then weekly for four weeks.]

The number of rescue antiemetic doses delivered as per the inpatient medication chart or the participants diary of medications as an outpatient.[+24hr, +48hrs, +72hrs from first study drug administration.]

Toxicity, assessed by adverse event list.[+24hrs, +48hrs, +72hrs since first study drug and then weekly for 4 weeks post intervention.]

Best nausea score over the preceding 24 hours, using an 11-point (0-10) numeric rating scale[measured at 72 hours from time of first study drug administration ]

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.[Assessed at 24 hours, 48 hours post first study drug administration.]

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.[Assessed at 24 hours, 48 hours post first study drug administration.]

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.[measured at 72 hours from time of first study drug administration ]

Secondary ID(s)

NIL

Source(s) of Monetary Support

NHMRC Research Grant

Secondary Sponsor(s)

The Queensland University of Technology

Ethics review

Status: Approved
Approval date:
Contact:

The Royal Brisbane and Women's Hospital HREC