Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
R&D number RO452
Study information
Scientific title
Acronym
Study hypothesis
Opioids are currently used in the management of breathlessness in palliative patients at the end of life. There is a small but growing evidence base regarding the use of opioids to manage breathlessness in lung cancer and Chronic Obstructive Pumonary Disease (COPD). A pilot placebo controlled crossover study involving oramorph in ten heart failure patients demonstrated symptom improvement and two studies involving opioids in exercise revealed an improvement in exercise tolerance. Morphine is also used clinically to treat acute pulmonary oedema. The manner in which opioids improve breathlessness is unclear, but is likely to represent a combination of local effects in the lung and heart, effect at the respiratory centre in the brain and neurohumeral effects. Our aim is to demonstrate a symptom benefit regarding breathlessness with opioids and to determine if this is a class effect and whether opioids that interact with different opioid receptors have different outcomes.
Ethics approval
Ethics approval received from the Leeds East Ethics Committee on the 9th October 2007 (ref: 07/H1306/110).
Study design
This study is a three arm randomised double blind placebo controlled clinical crossover trial. Participants and observers will remain blinded throughout.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic heart failure
Intervention
Please note that as of 29/04/2008 the anticipated start date of this trial was changed to 01/05/2008; the previous start date was 01/07/2007.
The two active intervention arms involve low dose oral liquid morphine (oramorph 5 mg four times a day [QDS]) and oral oxycodone liquid (oxynorm 2.5 mg QDS). The sequence of interventions will be randomised for each participant and all participants will receive all three treatment arms. Participants will be invited to take the medication (oramorph, oxynorm or placebo) for four consecutive days. There will be daily assessments of breathlessness and side effects during this time. A three-day washout period will occur before commencing the next treatment in sequence.
Intervention type
Drug
Phase
Not Specified
Drug names
Morphine (oramorph), oxycodone (oxynorm)
Primary outcome measure
Severity of breathlessness as measured by the Borg validated score for breathlessness and 11 point Numerical Rating Scale (worst, average and current readings), measured daily whilst taking the trial medications.
Secondary outcome measures
1. Distress from breathlessness, measured on days one and four for each trial medication (the first and last days participants take it)
2. Satisfaction and coping, measured daily whilst taking the trial medications
3. Breathlessness descriptors, measured on days one and four for each trial medication (the first and last days participants take it)
4. Adverse effect scores, measured daily whilst taking the trial medications
5. Quality of life, measured on days one and four for each trial medication (the first and last days participants take it)
Overall trial start date
01/05/2008
Overall trial end date
01/12/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. New York Heart Association (NYHA) grade three to four chronic heart failure with systolic dysfunction on echocardiography
2. Receiving optimal medical management (diuretics and Angiotensin Converting Enzymes [ACE] inhibitors/angiotensin 2 antagonists) stable for the past month
3. Aged 18 years and over
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
48
Participant exclusion criteria
1. Inadequate renal function (Glomerular Filtration Rate [GFR] less than 30 ml/min on Cockroft/Gault formula)
2. Morphine allergy
3. Currently receiving opioid therapy
Recruitment start date
01/05/2008
Recruitment end date
01/12/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Academic Cardiology
Hull
HU16 5JQ
United Kingdom
Sponsor information
Organisation
Hull and East Yorkshire Hospitals NHS Trust (UK)
Sponsor details
Research and Development Department
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2RJ
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Hull York Medical School (HYMS) Clinical Fellowship Scheme (funded by the NHS local Strategic Health Authority) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21712288
Publication citations
-
Results
Oxberry SG, Torgerson DJ, Bland JM, Clark AL, Cleland JG, Johnson MJ, Short-term opioids for breathlessness in stable chronic heart failure: a randomized controlled trial., Eur. J. Heart Fail., 2011, 13, 9, 1006-1012, doi: 10.1093/eurjhf/hfr068.