Haloperidol is a dopamine receptor blocker commonly used for the treatment of nausea in palliative care patients. Our previous research has shown haloperidol to be an effective antiemetic for nausea not related to anticancer treatment with a response rate at 3 days of 62%. Methotrimeprazine is a broad spectrum phenothiazine that acts at multiple receptor sites to cover a number of possible causes of nausea. Despite the wide use of this drug in palliative care, most of the evidence supporting its use is largely anecdotal. The aim of this study was to compare the antiemetic efficacy of methotrimeprazine with the standard haloperidol in a controlled trial.
Patients were randomized to receive either blinded encapsulated oral methotrimeprazine (6.25mg) or oral haloperidol (1.5mg) both given once daily. All other regular antiemetics were discontinued with metoclopramide 10mg q4hourly available as rescue. In the absence of response at 24 hours or 48 hours, the dose could be increased to twice daily (total daily dose 12.5mg methotrimeprazine or 3mg haloperidol). Assessments were undertaken every 24 hours. Response was defined as a ≥ 2 point improvement from baseline on an 11 point NRS for average nausea over the previous 24 hours. The primary endpoint was response at 72 hours. The use of rescue antiemetics, adverse effects and the complete control of nausea (response with an average nausea score of
121 patients were randomised to achieve the sample size of 50 participants per arm at Day 3 in March 2017. The trial remains unblinded subject to data cleansing. Preliminary analysis of Arm A vs Arm B reveals response rates of 86% and 71% respectively at 72 hours with complete response rates of 70% and 60%. Secondary analysis of response over time (days 1 to 3) shows no differences between arms.
Both methotrimeprazine and haloperidol are effective in the control of nausea in patients receiving palliative care with response rates of over 70% at 72 hours and no significant difference between arms. The choice of agent may depend on availability, cost and side-effect profile (yet to be analysed).
Clinical trial identification
Legal entity responsible for the study
Palliative Care Clinical Studies Collaborative
Australian Government National Health and Medical Research Council
All authors have declared no conflicts of interest.