Please select the outcome measures that correspond to the clinical trial below.
Title: A Pragmatic, Phase III, Multi-site, Double-blind, Placebo Controlled, Parallel Arm, Dose Increment Randomised Trial of Regular, Low Dose Extended Release Morphine for Chronic Refractory Breathlessness
Brief 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.


Options:
A: Change from baseline worst breathlessness intensity over the previous 24 hours (Week 1); Change from the baseline in the number of steps per day (Week 3)
B: To determine the impact of the intervention initiated after hospital discharge from a COPD exacerbation on the rate of COPD related re-hospitalizations in the intervention versus the control group . (12 months); To determine the impact of the intervention initiated after hospital discharge from a COPD exacerbation on the rate of the composite outcome, COPD related hospitalizations or death in the intervention versus the control group. (12 months)
C: Changes from baseline in the St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) total score at week 6 and 12 (Week 0, 6 and 12)
D: walked in meters in the six minute walking test (6MWT) (Unlike walking meters of baseline and one year)

Answer: A