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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02720822




Registration number
NCT02720822
Ethics application status
Date submitted
10/03/2016
Date registered
28/03/2016
Date last updated
11/02/2020

Titles & IDs
Public title
Breathlessness Exertion and Morphine Sulphate
Scientific 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
Secondary ID [1] 0 0
030/15
Universal Trial Number (UTN)
Trial acronym
BEAMS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 0 0
Dyspnea 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Morphine Sulfate
Treatment: Drugs - Plus laxative (Docusate with senna)
Treatment: Drugs - Plus placebo laxative
Treatment: Devices - FitBit charge HR (Accelerometer)

Placebo comparator: Placebo - Double-blind placebo capsule, looking identical to capsules with active treatment, during all three treatment weeks.

Experimental: Morphine Sulfate (0, 0, 8 mg) - Placebo on weeks one and two. Morphine 8 mg/day on week three.

Experimental: Morphine sulfate (0, 8, 8 mg) - Placebo on week one. Morphine 8 mg/day on weeks two and three.

Experimental: Morphine sulfate (0, 8, 16 mg) - Placebo on week one. Morphine 8 mg/day on week two. Morphine 16 mg/day on week three.

Experimental: Morphine sulfate (8, 8, 8 mg) - Morphine 8 mg/day on weeks one, two and three.

Experimental: Morphine sulfate (8, 8, 16 mg) - Morphine 8 mg/day on weeks one and two. Morphine 16 mg/day on week three.

Experimental: Morphine sulfate (8, 16, 16 mg) - Morphine 8 mg/day on week one. Morphine 16 mg/day on weeks two and three.

Experimental: Morphine sulfate (8, 16, 24 mg) - Morphine 8 mg/day on week one. Morphine 16 mg/day on week two. Morphine 24 mg/day on week three.

Experimental: Morphine sulfate (16, 16, 16 mg) - Morphine 16 mg/day on weeks one, two and three.

Experimental: Morphine sulfate (16, 16, 24 mg) - Morphine 16 mg/day on weeks one and two. Morphine 24 mg/day on week three.

Experimental: Morphine sulfate (16, 24, 24 mg) - Morphine 16 mg/day on week one. Morphine 24 mg/day on weeks two and three.

Experimental: Morphine sulfate (16, 24, 32 mg) - Morphine 16 mg/day on week one. Morphine 24 mg/day on week two. Morphine 32 mg/day on week three.


Treatment: Drugs: Placebo
Treatment with placebo is given as one double-blind capsule in the morning.

Treatment: Drugs: Morphine Sulfate
Treatment with sustained-release morphine sulfate is given as one double-blind capsule in the morning.

Treatment: Drugs: Plus laxative (Docusate with senna)
If patients are taking morphine, a laxative will be offered. This applies whatever the dose of morphine being taken (8mg, 16mg, 24mg or 32 mg).

Treatment: Drugs: Plus placebo laxative
If the patients are taking placebo, a placebo laxative will be offered.

Treatment: Devices: FitBit charge HR (Accelerometer)
A Fitbit will be worn by patients during week 1 and week 3.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline worst breathlessness intensity over the previous 24 hours
Timepoint [1] 0 0
Week 1
Primary outcome [2] 0 0
Change from the baseline in the number of steps per day
Timepoint [2] 0 0
Week 3
Secondary outcome [1] 0 0
Change from baseline end-tidal carbon dioxide
Timepoint [1] 0 0
Up to week 15
Secondary outcome [2] 0 0
Change from baseline pulse oximetry
Timepoint [2] 0 0
Up to week 15
Secondary outcome [3] 0 0
Change from baseline intensity of breathlessness "average"
Timepoint [3] 0 0
Up to week 15
Secondary outcome [4] 0 0
Change from baseline distress from breathlessness over the previous 24 hours
Timepoint [4] 0 0
Up to week 15
Secondary outcome [5] 0 0
Change from baseline perceived-impact of breathlessness
Timepoint [5] 0 0
Up to week 3
Secondary outcome [6] 0 0
Change from baseline functional impact of breathlessness
Timepoint [6] 0 0
Up to week 15
Secondary outcome [7] 0 0
Change from baseline sleep minutes
Timepoint [7] 0 0
Week 3
Secondary outcome [8] 0 0
Change from baseline sleep activity
Timepoint [8] 0 0
Week 3
Secondary outcome [9] 0 0
Change from baseline in activity levels
Timepoint [9] 0 0
Week 3
Secondary outcome [10] 0 0
Change from baseline total energy expenditure
Timepoint [10] 0 0
Week 3
Secondary outcome [11] 0 0
Change from baseline performance status
Timepoint [11] 0 0
Up to week 15
Secondary outcome [12] 0 0
Change from baseline activities of daily living
Timepoint [12] 0 0
Up to week 15
Secondary outcome [13] 0 0
Change from baseline in sleep quality
Timepoint [13] 0 0
Up to week 15
Secondary outcome [14] 0 0
Change from baseline in objective sleep testing
Timepoint [14] 0 0
Week 3
Secondary outcome [15] 0 0
Change from baseline Polysomnography
Timepoint [15] 0 0
Week 3
Secondary outcome [16] 0 0
Change from baseline Driving ability
Timepoint [16] 0 0
Week 3 + 2 days
Secondary outcome [17] 0 0
Pharmacogenetic opioid profile - Number of participants with UGT2B7*2 and *28 polymorphisms
Timepoint [17] 0 0
Baseline (1 day)
Secondary outcome [18] 0 0
Pharmacogenetic opioid profile - Number of participants with P-glycoprotein polymorphism (ABCB1 5SNPs in a haplotype block)
Timepoint [18] 0 0
Baseline (1 day)
Secondary outcome [19] 0 0
Pharmacogenetic opioid profile - Number of participants with 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572 polymorphism
Timepoint [19] 0 0
Baseline (1 day)
Secondary outcome [20] 0 0
Pharmacogenetic opioid profile - Mu receptor (A118G) polymorphism
Timepoint [20] 0 0
Baseline (1 day)
Secondary outcome [21] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine Peak Plasma Concentration [Cmax]
Timepoint [21] 0 0
Week 1
Secondary outcome [22] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine Area Under the Curve (AUC)
Timepoint [22] 0 0
Week 1
Secondary outcome [23] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-6-glucuronide (M6G) Peak Plasma Concentration [Cmax]
Timepoint [23] 0 0
Week 1
Secondary outcome [24] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-6-glucuronide (M6G) Area Under the Curve (AUC)
Timepoint [24] 0 0
Week 1
Secondary outcome [25] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-3-glucuronide (M3G) Peak Plasma Concentration [Cmax]
Timepoint [25] 0 0
Week 1
Secondary outcome [26] 0 0
Pharmacokinetic (PK)/ Pharmacodynamic (PD) opioid profile: Morphine-3-glucuronide (M3G) Area Under the Curve (AUC)
Timepoint [26] 0 0
Week 1
Secondary outcome [27] 0 0
Change from baseline serum testosterone level
Timepoint [27] 0 0
Week 15
Secondary outcome [28] 0 0
Adverse Effects
Timepoint [28] 0 0
Up to 15 weeks
Secondary outcome [29] 0 0
Change from baseline in concurrent symptoms
Timepoint [29] 0 0
Up to 15 weeks
Secondary outcome [30] 0 0
Change from the baseline anxiety and depression
Timepoint [30] 0 0
Up to Week 15
Secondary outcome [31] 0 0
Change in baseline global impression of change
Timepoint [31] 0 0
Up to 15 weeks
Secondary outcome [32] 0 0
Change from baseline health-related quality of life
Timepoint [32] 0 0
Up to 15 weeks
Secondary outcome [33] 0 0
Change from baseline health-status in COPD
Timepoint [33] 0 0
Week 3
Secondary outcome [34] 0 0
Blinded-patient preference to continue the treatment [3-point Likert Scale]
Timepoint [34] 0 0
Up to week 15
Secondary outcome [35] 0 0
Change from baseline caregiver Impact
Timepoint [35] 0 0
Up to week 15
Secondary outcome [36] 0 0
Economic Evaluation - Cost per responder
Timepoint [36] 0 0
Up to week 4
Secondary outcome [37] 0 0
Opioid Withdrawal
Timepoint [37] 0 0
Up to week 15 + 3 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Clare Holland House - Canberra
Recruitment hospital [2] 0 0
Concord Hospital - Concord
Recruitment hospital [3] 0 0
St Vincent's Hospital Sydney - Sacred Heart Hospice - Darlinghurst
Recruitment hospital [4] 0 0
Calvary Health Care Kogarah - Kogarah
Recruitment hospital [5] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 0 0
Westmead Hospital - Westmead
Recruitment hospital [7] 0 0
Prince Charles Hospital - Brisbane
Recruitment hospital [8] 0 0
Nambour Hospital - Sunshine Coast
Recruitment hospital [9] 0 0
Southern Adelaide Palliative Services - Adelaide
Recruitment hospital [10] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [11] 0 0
Barwon Health McKellar Centre - Geelong
Recruitment hospital [12] 0 0
The Austin Hospital - Heidelberg
Recruitment hospital [13] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [14] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2600 - Canberra
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
3590 - Kogarah
Recruitment postcode(s) [5] 0 0
2170 - Liverpool
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment postcode(s) [7] 0 0
4032 - Brisbane
Recruitment postcode(s) [8] 0 0
4560 - Sunshine Coast
Recruitment postcode(s) [9] 0 0
5041 - Adelaide
Recruitment postcode(s) [10] 0 0
3065 - Fitzroy
Recruitment postcode(s) [11] 0 0
3215 - Geelong
Recruitment postcode(s) [12] 0 0
3084 - Heidelberg
Recruitment postcode(s) [13] 0 0
3050 - Melbourne
Recruitment postcode(s) [14] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Flinders University
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David C Currow, MD, PhD
Address 0 0
Study Principal Investigator; Flinders University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.