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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
8/08/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/12/2019
Sample size
Target
171
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.

Results not provided in https://clinicaltrials.gov/study/NCT02720822