Opioids for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease

• Status: Withdrawn
• Trial end date: 2018-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Breathlessness, the sensation of breathing discomfort, is a major problem in people with chronic obstructive pulmonary disease (COPD). Breathlessness that persists despite optimal management of the underlying disease(s) is said to be refractory.

Preliminary evidence suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, this research on morphine for breathlessness has not defined the best way to adjust the dose of the medication, or refined which people are most likely to have benefit, no response or side effects.

This is a randomized, double-blind phase III trial in people with COPD and significant refractory breathlessness, which will explore several important questions:

• Are regular, low dose opioids (morphine) at four possible doses over 3 weeks more effective than placebo medication (containing no active ingredient) at improving breathlessness?

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

• What are the common side effects of this intervention?

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

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

Participants will be allocated to receive three weeks of morphine sulfate (and laxative, docusate with senna), or placebo (and placebo laxative). The dose of morphine may be increased each week for weeks two and three. All medicines will appear the same (blinded) and neither the doctor nor the participant will know which medication the participant is receiving.

Participants will have a medical interview, 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 3 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: Morphine

Criteria

Inclusion Criteria:

• 18 years of age or older.

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

• 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 two (2) or higher on the modified Medical Research Council (mMRC) dyspnoea scale

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

• Assessed as competent (using SLUMS score of 27 for high school, and 25 for less than high school)

• Able and willing to give written informed consent

Exclusion Criteria:

• On regularly prescribed opioid medications, including codeine preparations at or above 8mg oral morphine equivalent daily 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.

• Chronic alcoholism, or previous 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.