None listed
Conditions
Brief summary
Breathlessness is a very distressing and difficult symptom commonly experienced towards the end of life. There are published research findings to show that the use of low dose long acting morphine can help the sensation of breathlessness, without side effects such as drowsiness and respiratory depression. There are now even lower doses of sustained release morphine available than when initial studies were done which may offer similar benefits and potentially fewer side effects. Initial studies in this area were short (one week) and long term benefits and side effects have not been well studied. This study will try to determine the optimal dose of morphine for breathlessness, which may be lower or higher than those previously reported in the literature, and if there is long term benefit. This will be done through the use of a 2 stage study. In stage 1, consenting participants will start on a small dose of morphine for one week, and then slowly increase the dose if there has been no benefit over a period of up to 3 weeks according to the participant reports of breathlessness and side effects. Participants will be asked to complete a simple twice daily diary throughout stage one, and will be monitored by visits to their home weekly and telephone calls between visits by the study nurse. When participants have been on a dose of morphine for one week which provides relief from breathlessness, without side effects, they will be entered into the second stage of the study. The second stage will ask participants to continue on the morphine dose determined in stage one long term to determine if that dose continues to provide benefit over a prolonged period. Participants will be monitored via regular telephone calls for the duration of the study or until the participant withdraws. They will also be asked to maintain a simple weekly diary for this time to provide ongoing information about their response to the morphine and any side effects.
Interventions
Stage one. Open label dose ranging.
Eligible, consenting patients will be commenced on 10mg Sustained Release (SR) morphine (Kapanol) daily.
A diary will be completed twice daily by the participant for 2 days prior to intervention and then for 7 days. On Day 7 the participant will be visited at home and assessed for;
1. Side effects. Little or no side effects will continue the assessment.
2. Benefit. The participant will then be assessed for benefit from the intervention. No benefit will lead
Stage one. Open label dose ranging. Eligible, consenting patients will be commenced on 10mg Sustained Release (SR) morphine (Kapanol) daily. A diary will be completed twice daily by the participant for 2 days prior to intervention and then for 7 days. On Day 7 the participant will be visited at home and assessed for; 1. Side effects. Little or no side effects will continue the assessment. 2. Benefit. The participant will then be assessed for benefit from the intervention. No benefit will lead to an increased dose of SR morphine by 10mg for a further 7 days. Participants will continue increasing doses of SR morphine until a dose provides benefit without side effects (to a maximum of 30mg daily). If participants continue to 30mg without side effects, but also without benefit they exit the study at that point and do not continue to stage 2. Stage two. Long term effectiveness study. Eligible participants will have reached a SR morphine dose where side effects are absent (or acceptable/minimal) and benefit has been established. Participants will remain on the dose established as part of Stage one. A diary will be completed at weekly intervals to record ongoing dyspnoea scores, ongoing acceptability, and the emergence of any complications. In addition, participants will be monitored by telephone weekly for 2 months, then monthly until exit from the study. Stage two will continue until • Participant withdraws • The participant is withdrawn, if the AKPS score falls to 30 or below • Study completion; until participant numbers have been reached,. • Or until death Follow-up will include file review for hospitalisation, cessation of opioids, and introduction of other therapies such as oxygen.
Sponsors
Repatriation General Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Specialist relevant has assessed participant to have received maximal treatment (including reversing anaemia) • On stable medications for the previous 7 days• Participant has dyspnoea score greater than or equal to 2 on the Modified Medical Research Council dyspnoea scale • In the treating clinician's estimation, the participant has a prognosis of at least one month.• On stable oxygen needs.
Exclusion criteria
Pregnancy, any chance of pregnancy, or breastfeeding• On regular opioid medications, including codeine preparations. • Confusion (MMSE<24/30)• AKPS score of <50• Uncontrolled nausea or vomiting.• True adverse reaction(s) or hypersensitivity to previous opioids.• A creatinine clearance of <15ml/min. • Gastrointestinal obstruction.• Concomitant use of Monoamine Oxidase Inhibitor(s) (MAOIs) in the last 2 weeks.• Past history of substance misuse• Unwilling or unable to complete study measures.
Outcome results
None listed