Please select the arm or intervention descriptions that belong 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: Arm Label: Placebo; Type: PLACEBO_COMPARATOR; Interventions: Drug: Placebo, Drug: Plus placebo laxative, Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine Sulfate (0, 0, 8 mg); Type: EXPERIMENTAL; Interventions: Drug: Placebo, Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Drug: Plus placebo laxative, Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (0, 8, 8 mg); Type: EXPERIMENTAL; Interventions: Drug: Placebo, Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Drug: Plus placebo laxative, Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (0, 8, 16 mg); Type: EXPERIMENTAL; Interventions: Drug: Placebo, Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Drug: Plus placebo laxative, Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (8, 8, 8 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (8, 8, 16 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (8, 16, 16 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (8, 16, 24 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (16, 16, 16 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (16, 16, 24 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (16, 24, 24 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Arm Label: Morphine sulfate (16, 24, 32 mg); Type: EXPERIMENTAL; Interventions: Drug: Morphine Sulfate, Drug: Plus laxative (Docusate with senna), Device: FitBit charge HR (Accelerometer) | Intervention Type: DRUG; Name: Placebo; Assigned to Arm(s): Morphine Sulfate (0, 0, 8 mg), Morphine sulfate (0, 8, 16 mg), Morphine sulfate (0, 8, 8 mg), Placebo | Intervention Type: DRUG; Name: Morphine Sulfate; Assigned to Arm(s): Morphine Sulfate (0, 0, 8 mg), Morphine sulfate (0, 8, 16 mg), Morphine sulfate (0, 8, 8 mg), Morphine sulfate (16, 16, 16 mg), Morphine sulfate (16, 16, 24 mg), Morphine sulfate (16, 24, 24 mg), Morphine sulfate (16, 24, 32 mg), Morphine sulfate (8, 16, 16 mg), Morphine sulfate (8, 16, 24 mg), Morphine sulfate (8, 8, 16 mg), Morphine sulfate (8, 8, 8 mg) | Intervention Type: DRUG; Name: Plus laxative (Docusate with senna); Assigned to Arm(s): Morphine Sulfate (0, 0, 8 mg), Morphine sulfate (0, 8, 16 mg), Morphine sulfate (0, 8, 8 mg), Morphine sulfate (16, 16, 16 mg), Morphine sulfate (16, 16, 24 mg), Morphine sulfate (16, 24, 24 mg), Morphine sulfate (16, 24, 32 mg), Morphine sulfate (8, 16, 16 mg), Morphine sulfate (8, 16, 24 mg), Morphine sulfate (8, 8, 16 mg), Morphine sulfate (8, 8, 8 mg) | Intervention Type: DRUG; Name: Plus placebo laxative; Assigned to Arm(s): Morphine Sulfate (0, 0, 8 mg), Morphine sulfate (0, 8, 16 mg), Morphine sulfate (0, 8, 8 mg), Placebo | Intervention Type: DEVICE; Name: FitBit charge HR (Accelerometer); Assigned to Arm(s): Morphine Sulfate (0, 0, 8 mg), Morphine sulfate (0, 8, 16 mg), Morphine sulfate (0, 8, 8 mg), Morphine sulfate (16, 16, 16 mg), Morphine sulfate (16, 16, 24 mg), Morphine sulfate (16, 24, 24 mg), Morphine sulfate (16, 24, 32 mg), Morphine sulfate (8, 16, 16 mg), Morphine sulfate (8, 16, 24 mg), Morphine sulfate (8, 8, 16 mg), Morphine sulfate (8, 8, 8 mg), Placebo
B: Arm Label: Activity-Self Management; Type: EXPERIMENTAL; Interventions: Behavioral: Self-Management and Motivational Interviewing | Arm Label: Usual Care; Type: NO_INTERVENTION; Interventions: N/A | Intervention Type: BEHAVIORAL; Name: Self-Management and Motivational Interviewing; Assigned to Arm(s): Activity-Self Management
C: Arm Label: Arm A (myAIRVO2® + HOT, HOT); Type: EXPERIMENTAL; Interventions: Device: High-flow nasal cannula therapy, Device: Home oxygen therapy (HOT) | Arm Label: Arm B (HOT, myAIRVO2® + HOT); Type: EXPERIMENTAL; Interventions: Device: High-flow nasal cannula therapy, Device: Home oxygen therapy (HOT) | Intervention Type: DEVICE; Name: High-flow nasal cannula therapy; Assigned to Arm(s): Arm A (myAIRVO2® + HOT, HOT), Arm B (HOT, myAIRVO2® + HOT) | Intervention Type: DEVICE; Name: Home oxygen therapy (HOT); Assigned to Arm(s): Arm A (myAIRVO2® + HOT, HOT), Arm B (HOT, myAIRVO2® + HOT)
D: Arm Label: rehabilitation program more the urban circuit; Type: EXPERIMENTAL; Interventions: Other: rehabilitation more the urban circuit | Arm Label: rehabilitation program non circuit group .; Type: EXPERIMENTAL; Interventions: Other: rehabilitation program but not given urbane circuits | Intervention Type: OTHER; Name: rehabilitation more the urban circuit; Assigned to Arm(s): rehabilitation program more the urban circuit | Intervention Type: OTHER; Name: rehabilitation program but not given urbane circuits; Assigned to Arm(s): rehabilitation program non circuit group .

Answer: A