Breathlessness Exertion and Morphine Sulphate

• Status: Completed
• Trial end date: 2019-12-20
• Target enrollment: 0
• Participant gender: All

Summary

Breathlessness is an overwhelming symptom affecting tens of thousands of Australians every day. For many people, it persists even when all the underlying causes have been optimally managed (chronic breathlessness). In these circumstances, it often occurs at rest or with minimal exertion.

Evidence from a number of clinical studies suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, it is not well established which patients derive more benefit and what is the net clinical effect of this treatment (weighing benefits and harms).

This is a phase III, multi-site, randomised, double-blind, placebo-controlled trial with patients with chronic obstructive pulmonary disease (COPD) and severe chronic breathlessness which will explore several important questions:

• Are regular, low doses of morphine at four possible doses over 3 weeks more effective than placebo at improving breathlessness?

• Does increasing the dose in people who already are experiencing some benefit provide even greater reduction in worst breathlessness?

• Does the medication have any effect on daily activity and quality of life?

• What are the common or serious side effects of this intervention?

• Does the benefit from the medication outweigh the side effects it produces?

• Are there specific characteristics of people who are more likely to receive benefit from extended release morphine?

Participants will receive once daily extended release morphine (plus laxative, docusate with senna), or placebo (placebo laxative) in addition to their usual medication for up to 3 weeks at increasing doses.

Participants will have a medical interview and physical examination to collect some general health information, and baseline measurements including; daily activity, symptoms, and quality of life. A small amount of blood may be required to check eligibility. Further blood samples may be taken at week 1 and 3 to enable testing on how individuals respond to opioids, further consent will be obtained for these samples.

Data on benefits, side effects, and medical care will be collected during comprehensive weekly visits. Participants will also fill out a simple diary twice daily for weeks one to three of the study, and for one day each week during an optional 6 month extension stage.

The outcome of this study may enable better management of symptoms and activity in people COPD with medicines that are shown to be effective and safe.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Flinders University
• Treatments: Cathartics; Laxatives; Morphine

Criteria

Inclusion Criteria:

• 18 years of age or older.

• Physician diagnosed COPD confirmed by spirometry with the most recent result available defined as a prior post-bronchodilator FEV1/FVC < 0.7 in accordance with the GOLD 2014 criteria.

• Respiratory physician confirmed optimisation of treatment of COPD.

• On stable medications relating to the optimal treatment of COPD or its symptomatic management over the prior week except routine "as needed" medications.

• Breathlessness of a level three (3) or four (4) on the modified Medical Research Council (mMRC) breathlessness scale.

• worst breathlessness intensity in the previous 24 hours was at least 3/10 on a 0-10 numerical rating scale (NRS).

• English speaking with sufficient reading and writing ability to complete the study questionnaires

• Assessed as competent (using St Louise University Mental Status Examination (SLUMS) score of 27/30 for people whose highest level of education was high school, and 25/30 for people who did not complete high school).

• Able and willing to give written informed consent.

Exclusion Criteria:

• On any opioid for breathlessness in the previous seven (7) days.

• On regularly prescribed opioid medications for other conditions, including codeine preparations at or above 8mg oral morphine equivalent daily dose (MEDD) in the previous seven (7) days.

• History of adverse reactions to any of the study medications or constituents in the placebo;

• Australian-modified Karnofsky performance score (AKPS) less than 50 at the beginning of the study.

• Respiratory or cardiac event in the previous one week (excluding upper respiratory tract infections). Illness must have resolved completely prior to baseline evaluation, as judged by the person's treating physician.

• Evidence of respiratory depression with resting respiratory rate <8/min.

• Documented central hypoventilation syndrome.

• Current history of abuse of alcohol, or recent history of substance misuse.

• Uncontrolled nausea, vomiting or evidence of a gastrointestinal tract obstruction.

• Renal dysfunction with creatinine clearance calculated (MDRD) less than 20 mls/minute.

• Evidence of severe hepatic impairment defined as transaminases or bilirubin >4x normal (Excluding Gilbert's syndrome)

• Pregnant or breastfeeding.