Opioids in the management of breathlessness in advanced heart failure

ISRCTN	ISRCTN85268059
DOI	https://doi.org/10.1186/ISRCTN85268059
Secondary identifying numbers	R&D number RO452

Submission date: 03/05/2007
Registration date: 04/09/2007
Last edited: 04/07/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Stephen Oxberry
Scientific

Academic Cardiology
Xray 3 Building
Castle Hill Hospital
Castle Road
Cottingham
Hull
HU16 5JQ
United Kingdom

Study information

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
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study objectives	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(s)	Ethics approval received from the Leeds East Ethics Committee on the 9th October 2007 (ref: 07/H1306/110).
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	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 study start date	01/05/2008
Completion date	01/12/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	48
Key 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
Key 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
Date of first enrolment	01/05/2008
Date of final enrolment	01/12/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Academic Cardiology

Hull
HU16 5JQ
United Kingdom

Sponsor information

Hull and East Yorkshire Hospitals NHS Trust (UK)
Hospital/treatment centre

Research and Development Department
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2RJ
England
United Kingdom

Website	http://www.hey.nhs.uk/
"ROR"	https://ror.org/01b11x021

Funders

Funder type

Government

Hull York Medical School (HYMS) Clinical Fellowship Scheme (funded by the NHS local Strategic Health Authority) (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2011		Yes	No