Extract

Background and study aims Breathlessness is distressing for people with heart failure, and, as the condition worsens, may persist despite the best treatment. Low-dose morphine safely improves breathlessness in other conditions such as cancer and chronic obstructive pulmonary disease (COPD), but we do not know if it helps in heart failure as the two existing studies (of morphine use for 4 days) found different results. There is, however, observed breathing benefit in people with heart failure who have taken morphine for 3 months, but we cannot be confident about this finding as it may have occurred due to chance. Our main aim is to find out whether low-dose morphine therapy taken daily for at least one month is better than a 'dummy' medicine (placebo) for the relief of breathlessness in people with chronic heart failure who are still breathless despite being on the best treatment for their heart condition. We also aim to see whether morphine helps any distress due to breathlessness, enables coping with breathlessness, increases exercise and activity, quality of sleep, quality of life, use of health care services and the severity of the heart failure itself. By comparing morphine with the placebo medicine over 3 months, we aim to find out the unwanted effects due to the morphine itself especially on daytime drowsiness, nausea, constipation and confusion. Who can participate? Men and women with heart failure and persistent symptoms despite standard heart failure care. What does the study involve? Participants will be randomly allocated (by chance) to receive either low-dose morphine as a capsule taken twice a day or an identical placebo capsule. As constipation is a common side-effect of morphine, all participants taking active morphine will have laxative capsules, and all those taking placebo morphine will have identical 'dummy laxative' capsules. Other than this, all participants will receive the same care and follow up. Benefit from morphine will be calculated at 1 month, but the whole study per participant will last for 3 months so we can gain the best understanding of unwanted effects and any further improvement over that time. Participants will be required to attend the research clinic two times over 3 months. Other assessments can be done by phone or the research nurse can visit at home. Participants will complete the study questionnaires and measures when needed (the research nurse will help) and continue with any treatment the usual medical team advises. The study will measure quality of life, severity of breathlessness and other symptoms (pain, sleepiness, cognition) using questionnaires. The level of exercise that participants are able to do comfortably will be measured in the clinic with a 6-minute walk test. Activity will also be measured using an activity monitor (like a small matchbox) on the thigh under the clothes, attached with double-sided sticky tape. It can be taken off and repositioned if needed. This measures the number of steps taken and the time spent sitting or lying down. It will be worn for 7 days before the study starts and again during the last 7 days of the first month. What are the possible benefits and risks of participating? Although this study may not directly benefit participants, it may improve future treatment of breathlessness. Morphine has been used in medical practice for many years. We therefore know what side-effects might occur. Most patients cope very well with the low doses of morphine that we intend to use. We will check regularly about the known side effects that people can get. These include nausea or feeling sick, constipation or sleepiness. In some people concentration may be affected until they get used to the steady dose after a few days. Therefore participants will be advised not to drive during the first week of taking the medicine. After this time they should carefully consider whether concentration is affected before driving - if in doubt, they should not drive. If side effects persist which may affect driving, participants would need to inform the DVLA. As with any other change in medication, participants should inform their motor insurance company to ensure cover is valid. Although people may worry about becoming addicted to morphine, we rarely see this in people who take it for health reasons. However, if the body has become accustomed to morphine over time, then it may take a few days to readjust when morphine is stopped. This is not expected to be an issue with this study but all participants will receive a phone call in the few days after the end of the study to check all is well. Where is the study run from? The study is run from the Castle Hill Hospital in Hull, UK as the lead centre. About 12 centres in England and Scotland will be involved with each centre recruiting 1-2 participants per month. When is the study starting and how long is it expected to run for? The study started recruitment in September 2015. Recruitment will be open for up to two years. Who is funding the study? The British Heart Foundation, UK. Who is the main contact? Professor Miriam Johnson [email protected]

Inclusion criteria

• Heart Failure, including failure due to left ventricular dysfunction and failure with preserved ejection fraction

Links

• isrctn
• ictrp