None listed
Conditions
Brief summary
In some cases, nausea remains refractory to treatment despite multiple lines of treatment, often in combination. This is a randomised controlled double-blind trial evaluating the effectiveness of one drug (levomepromazine) against placebo with rescue antiemetics (BSC) in both arms in patients with nausea that has been demonstrated to be refractory to standard guideline driven targeted antiemetic therapy or single agent therapy with haloperidol. This test drug has not yet been rigorously evaluated in this setting and does not yet have a registered indication for use in palliative care. The hypothesis to be tested is that for cancer patients with nausea not related to anticancer treatment, there is no difference in response at 72 hours to levomepromazine versus a placebo with rescue antiemetics. Response to treatment is defined as a minimum two point improvement from baseline and end score <3 on an 11 point (0-10) numeric rating scale for average nausea in the previous 24 hours, measured 72 hours after treatment.
Interventions
This is a multi-centre randomised controlled double-blind trial evaluating the effectiveness of one agent unlicensed for this indication versus placebo with best supportive care (BSC) rescue in both arms, in improving the management of refractory nausea in patients with advanced cancer.
The interventions will be administered in a 3-step escalated dosing schedule over 72 hours. Treatment period is 3x24 hour periods. The daily dosing schedule is fixed. All syringes will be identical and prepared
This is a multi-centre randomised controlled double-blind trial evaluating the effectiveness of one agent unlicensed for this indication versus placebo with best supportive care (BSC) rescue in both arms, in improving the management of refractory nausea in patients with advanced cancer. The interventions will be administered in a 3-step escalated dosing schedule over 72 hours. Treatment period is 3x24 hour periods. The daily dosing schedule is fixed. All syringes will be identical and prepared by the pharmacists according to the randomisation schedule. Treatment allocation will not be disclosed to study staff, treating clinicians or investigators. The last dose must be given at least 6 hours prior to each response assessment. All doses will be administered subcutaneously or intravenously. The mode of administration will be determined by the clinician based on patient characteristics. BSC rescue therapy will be available in both arms over the 72 hours. BSC is defined as any Pharmaceutical Benefits Scheme (PBS) approved antiemetic or combination of PBS approved antiemetics at any dose or route thought appropriate by the investigator, given “as required” (prn) for nausea control. Each patient will have access to laxatives according to the practice of the treating clinician. Arm1 Levomepromazine (methotrimeprazine, Nozinan Registered Trademark (R)). 3.125mg-9.375mg per 24 hours delivered subcutaneously or intravenously in multiples of 3.125mg/2ml. Treatment period: 3 X 24 hours. Day 1= single dose at 0 hours (3.125mg) Day 2 (after 24 hours) = twice daily (6.25mg/24hours) Day 3 (after 48 hours) = 3 times per day (9.375mg/24 hours). Patients will be followed up for a maximum of 4 weeks after the primary endpoint for ongoing nausea control and safety.
Sponsors
Professor Patsy Yates
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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); have refractory nausea despite adequate treatment (as defined below); are able to comply with all trial requirements; are able to provide fully informed consent. Refractory nausea is defined as: 1. nausea rated as greater than or equal to 3/10 on a NRS for average nausea after completion of study 1; or 2. nausea rated as greater than or equal to 3/10 at baseline despite the use of: appropriate antiemetics at sufficient dose (step 3) as specified in the study 1 targeted guideline category or haloperidol 3mg/24hrs or promethazine 25mg po tds (25mg sc 24 hrly) or metoclopramide 60mg/24hrs or domperidone 20mg qid or cyclizine 100mg/24hrs (75mg/24hrs in the elderly) or ondansetron 8mg/day or 3. nausea rated as greater than or equal to 3/10 at baseline if appropriate antiemetics, or any of those listed above, have not been tolerated because of side-effects. If patients have been on antiemetic combinations, at least one of the agents must have been given at doses as specified above.
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 or placebo would not be appropriate (e.g. dexamethasone for acutely raised ICP); have undergone a procedure or intervention with the potential to affect nausea within 2 days prior to the study or are likely to undergo a procedure or intervention with the potential to affect nausea during the 3 day study period; have received levomepromazine within the last 3 days; if on corticosteroids, the dose has changed within 48 hours prior to study; have a definite contraindication to levomepromazine (e.g. severe hepatic impairment (LFTs > 5 x upper limit of normal (this applies to AST, ALT or bilirubin but not to ALP or GGT measurements)), symptomatic postural hypotension); have had a previous adverse reaction to the study medication; are pregnant or breastfeeding; have participated in a trial of a new clinical entity within the last 28 days
Outcome results
None listed