Morphine for palliative treatment of refractory dyspnea in patients with advanced COPD: benefits and respiratory adverse effects

Dyspnea is the most reported symptom of patients with advanced Chronic
Obstructive Pulmonary Disease (COPD) and is undertreated. Morphine is an
effective treatment for dyspnea and is recommended in current guidelines, but
questions about use of morphine in patients with COPD remain. For example, the
effect on health-related quality of life and functional capacity remains
unknown. Moreover, in one-third of the patients oral sustained release morphine
(morphine SR) does not relieve dyspnea and to date it remains unknown whether
severity of dyspnea and descriptors of breathlessness may predict a response to
morphine. Finally, cost-effectiveness is unknown. Therefore, prescription of
morphine to patients with advanced COPD and severe dyspnea is limited.

Primary objectives are:
1.1) to study the effect of oral administration of morphine SR on
health-related quality of life;
1.2) to explore whether morphine SR leads to respiratory adverse effects in
patients with advanced COPD.

Secondary objectives are:
2.1) to study the effect on functional capacity;
2.2) to explore whether description and severity of breathlessness are related
with a clinically relevant response to morphine;
2.3) to analyse the cost-effectives of morphine SR in patients with advanced
COPD.

double-blind placebo controlled intervention study, followed by a cohortstudy.

Patients will be randomized in an intervention group receiving morphine SR and
a control group receiving placebo. At the end of the intervention period, the
patients can choose to continue the morphine treatment.

Participants will be asked to complete a baseline and outcome-assessment (two
site visits between 2 and 3 hours); diary cards (four weeks); two home visits
(1 hour each) and two phone calls (0.5 hour each) within four weeks. They will
be asked to complete questionnaires and perform 4 times a Timed *Up & Go* test.
Two arterial blood gases will be drawn. Lung function will be measured.
Furthermore, overnight oximetry will be performed twice at their own homes.
Finally, a package of several questionnaires will be sent to their home address
4, 8 and 12 weeks after completion of the intervention period. They will be
asked to complete these questionnaires.
Patients may experience adverse affects of morphine like nausea, constipation,
and drowsiness. Adverse affects will be monitored closely and will be minimized
because the maximum dosage of morphine will be 30mg per day. Patients will
receive laxatives to prevent constipation and anti-emetics to prevent nausea.