Diamorphine or Alfentanil for Subcutaneous Use in Hospice In-patients? (DASH)

• The change in MDAS will be calculated from day 0 to day 3 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise. [ Time Frame: day 3 ] [ Designated as safety issue: Yes ]
  

• Change in MDAS between Days 0 and 7 [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  The change in MDAS will be calculated from day 0 to day 7 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• The change in the BPI-SF [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]
  The change in BPI-SF will be calculated from day 0 to day 3 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• The change in BPI-SF [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  The change in BPI-SF will be calculated from day 0 to day 7 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• The difference in proportion of patients taking laxatives [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
  The difference in proportion of patients taking laxatives will be compared between the two groups using the confidence interval on the difference of two proportions.
  
  
• The change in nausea visual analogue scale [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]
  The change in nausea visual analogue scale will be calculated from day 0 to day 3 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• Change in the number of vomits [ Time Frame: Day3 ] [ Designated as safety issue: Yes ]
  The change in number of vomits will be calculated from day 0 to day 3 and compared between the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• Change in nausea visual analogue scale [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  The change in nausea visual analogue scale will be calculated from day 0 to day 7 and compared betwen the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-WhitneyU test otherwise
  
  
• Change in the number of vomits [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  The change in number of vomits will be calculated from day 0 to day 7 and compared betwen the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-Whitney U test otherwise.
  
  
• Change in the total dosage of breakthrough medication (number of doses x dosage) [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]
  The change in the total dosage of breakthrough medication will be calculated from day 0 to day 3 and compared betwen the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-WhitneyU test otherwise
  
  
• Change in the total dosage of breakthrough medication (number of doses x dosage) [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
  The change in the total dosage of breakthrough medication will be calculated from day 0 to day 7 and compared betwen the two groups using a t-test if the data are sufficiently normally distributed, or the Mann-WhitneyU test otherwise
  
  

STUDY DESIGN

Study 1 - Open Label Pilot Day - 1 Hospice in-patients who are thought by a clinician to need subcutaneous strong opioids will be asked if they wish to take part in the study.

They will be given a patient information leaflet and a 'cooling off period' (a minimum of 1 day) to think about it. If the clinician feels that strong parenteral opioids are needed diamorphine will be commenced immediately (as standard practice).

Day 0 If the patient agrees to take part in the trial they will be asked to complete a consent form and this will be stored with the patient's notes.

The following assessments will be performed:

1. McGill Pain Questionnaire Short Form(MPQ-SF)
2. Brief Pain Inventory Short Form (BPI-SF)These measures were recommended by an EAPC Expert Working Group for pain syndrome characterization
3. Memorial Delirium Assessment Scale (MDAS). This has been validated in an advanced cancer population and used recently with hospice in-patients.
4. Nausea Visual Analogue Scale (VAS)
5. Nausea Duration over last 24 hours
6. Number of vomits in previous 24 hours

Randomisation Once baseline measures are completed the participant will be randomised using the next available of a series of numbered, opaque, sealed envelopes. These will be prepared remotely. Blocking will be used to prevent an imbalance in terms of the number allocated to each group. Block size will be appropriate to the size of the study and not be divulged to the investigators responsible for consent and revealing the allocation. This will reduce the risk of investigators anticipating the allocation for particular patients. A study log will be kept on site where participant details will be completed before the envelope is opened.

Subsequent Days

On each subsequent day the following assessments will be performed:

1. BPI-SF
2. MDAS
3. Nausea VAS

4. Number of vomits in previous 24 hours

   In addition the following measurements will be taken:

5. Stool chart for previous 24 hours
6. Breakthrough medication (number of doses and dosage) used
7. Laxatives taken
8. Other changes to medication

Patients will cease participation after assessment on day 7.