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Trial registered on ANZCTR


Registration number
ACTRN12615000841572
Ethics application status
Approved
Date submitted
24/07/2015
Date registered
13/08/2015
Date last updated
13/08/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized controlled trial of respiratory muscle training after a pleurodesis for malignant pleural effusion
Scientific title
The effect of respiratory muscle training to strengthen the inspiratory muscles after a pleurodesis for malignant pleural effusion
Secondary ID [1] 287145 0
nil
Universal Trial Number (UTN)
U1111-1172-5337
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Effusion 295697 0
Condition category
Condition code
Respiratory 295980 295980 0 0
Other respiratory disorders / diseases
Cancer 295981 295981 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
3 weeks after a pleurodesis to control MPE, patients will undergo a single blinded randomized controlled trial.
The intervention arm will receive inspiratory muscle strength training (IMT), requiring patients to take 30 deep forceful breaths (in 5-7 minutes) twice daily for 6 weeks through a Powerbreathe Medic device with an inspiratory threshold load initially set at approximately 40% of Maximum Inspiratory Pressure (MIP) and increased as tolerated.
The Powerbreathe device is a small handheld device held up to the mouth which provides resistance during inhalation. The initial 5-7 minute training session will be supervised by the principal investigator who is a Thoracic Physician, after baseline assessment. 30 minutes instruction on how to use the Powerbreathe Medic will be provided at this time. A 5-7 minute session of training supervised by a Thoracic Physician will be repeated after 2 and 4 weeks of home training. The principal investigator will prescribe increased threshold load each week, by approximately 10% of baseline MIP, after weekly 10 minute phone call. Adherence will be monitored with diaries.
Intervention code [1] 292411 0
Treatment: Devices
Comparator / control treatment
The comparator arm will perform deep breathing exercises through a Powerbreathe Medic device with complete lung inflation, using the same number of breaths twice daily for 6 weeks. This arm will not perform strength training as the inspiratory threshold load will be set at less than 5 cms H2O, and less than 15% of MIP.
Control group
Active

Outcomes
Primary outcome [1] 295655 0
Change from baseline of Maximum Inspiratory Pressure (pressure generated by the inspiratory muscles, a measure of inspiratory muscle strength). This is assessed with Powerbreathe KH2 device, and custom pressure tranducers.
Timepoint [1] 295655 0
Change of Maximum Inspiratory Pressure from baseline (before intervention) to 6 weeks (end of intervention).
Secondary outcome [1] 316116 0
Maximum Inspiratory Pressure assessed with Powerbreathe KH2 device
Timepoint [1] 316116 0
Baseline, 2 weeks, 4 weeks, 6 weeks
Secondary outcome [2] 316117 0
Oxygen cost of hyperpnea (mls of oxygen used for each L increase in ventilation) assessed with a metabolic cart sampling mixed expired gases, and a pneumotachograph sampling inspired flow.
Timepoint [2] 316117 0
Baseline (before start of intervention) and 6 weeks (end of intervention).
Secondary outcome [3] 316118 0
Forced Vital Capacity assessed with pneumotachograph.
Timepoint [3] 316118 0
Baseline (before start of intervention) and 6 weeks (end of intervention).
Secondary outcome [4] 316119 0
Inspiratory Capacity assessed with pneumotachograph.
Timepoint [4] 316119 0
Baseline (before start of intervention) and 6 weeks (end of intervention).
Secondary outcome [5] 316120 0
Diaphragm thickness assessed with linear high frequency ultrasound at end-expiration in zone of apposition contralateral to Malignant Pleural Effusion.
Timepoint [5] 316120 0
Baseline (before start of intervention) and 6 weeks (end of intervention).
Secondary outcome [6] 316121 0
Dyspnea-12, a questionnaire to measure shortness of breath experienced in daily life
Timepoint [6] 316121 0
Baseline (before start of intervention), and 2, 4, 6, 7, 8, 12 ,18, 26 weeks after baseline visit.
Secondary outcome [7] 316122 0
EQ-5D-5L, a questionnaire with Visual Analogue Scale to measure quality of life in cancer patients.
Timepoint [7] 316122 0
Baseline (before start of intervention), and 2, 4, 6, 7, 8, 12 ,18, 26 weeks after baseline visit.
Secondary outcome [8] 316123 0
Proportion of patients requiring further pleural drainage procedure, assessed by telephone interview.
Timepoint [8] 316123 0
Reported at 2, 4, 6, 7, 8, 12 ,18, 26 weeks after baseline visit.
Secondary outcome [9] 316124 0
Pneumonia, defined as new radiologic infiltrate requiring antibiotic therapy, assessed by phone interview and if required review of hospital records.
Timepoint [9] 316124 0
Reported at 2, 4, 6, 7, 8, 12 ,18, 26 weeks after baseline visit.

Eligibility
Key inclusion criteria
1. Malignant Pleural Effusion (defined as fluid around lung caused by cancer infiltrating the pleura): diagnosed on basis of (a) pleural fluid cytology or biopsy, or (b) a large exudative pleural effusion with no other cause identified and disseminated extra-thoracic malignancy.
2. Participants have undergone a pleurodesis 3 weeks prior to study entry. Pleurodesis may be either surgical (VATS or thoracoscopy) or closed chest tube pleurodesis.
3. No significant fluid re-accumulation on clinical assessment 3 weeks after a pleurodesis.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Expected survival < 3 months
WHO performance status 3 or 4
Body mass index less than 19 or greater than 40
Hypoxia requiring long term oxygen therapy
Severe cardiac or pulmonary disease causing dyspnea
Neurologic disease which may affect respiratory muscle strength, or co-operation with testing
Long term steroid therapy
Significant chest pain which might interfere with breathing tests and training
Pleural tumour greater than 20 mm thickness on CT chest
Recent pneumothorax
Severe osteoporosis (t score <-3.5), or history of spontaneous rib fractures
Rib metastasis
Chest wall deformity (kyphoscoliosis)
Perforated ear drum or symptoms of eustachian tube insufficiency
Language barrier or other significant communication difficulty
Women who are pregnant

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)
Randomization will be concealed from the primary investigator and stratified according to MIP > or < 70% predicted, as there is wide variability of MIP in patients with MPE. In other clinical populations such as COPD, IMT has greater effect in patients with lower baseline MIP. Randomization will use a 1:1 allocation which is restricted using random block sizes. The allocation sequence and block size will be concealed from the principal investigator who enrols, trains and assesses patients. The allocation sequence will be concealed in sequentially numbered, opaque, sealed and stapled envelopes. Aluminium foil inside the envelope will render the envelope impermeable to intense light. Envelopes will only be opened to allocate the respiratory muscle training intervention after participants complete all baseline (visit 1) assessments. There will be a witnessed signature that each envelope was sealed just prior to randomization.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random number generator will determine the order of the random block sizes. A random number generator will determine the order of allocation within each block, until allocation is required to be non-random to achieve balanced allocation within the block.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Blinding: Patients will be blinded to the nature of the intervention although they will receive coaching to ensure they are aware how to correctly complete the assigned breathing exercise. The principal investigator will not be blinded as this is not feasible while controlling the threshold load intervention. Symptom and quality of life instruments are completed by patients with no influence by the investigator, and oxygen cost of hyperpnea is an effort independent physiologic outcome.The principal investigator will perform the effort dependent MIP test with a standard protocol (5 MIP replicates per test, with scripted instructions and ATS criteria for performing additional replicates).
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size is based on change in Maximum Inspiratory Pressure (MIP) as the primary outcome:
Based on SD of 10.8 cms H2O for change in MIP, when 15 patients complete each arm, this study will have 80% power to demonstrate a =11 cms H2O increase in MIP due to respiratory muscle training, with a two-sided significance level of 0.05. Allowing for a drop-out rate of 20%, the recruitment target is 36 patients over 6 months, in order that 30 participants complete the intervention.
Unpaired t test will compare the change from baseline over 6 weeks between the two interventions:
MIP (primary outcome)
Forced Vital Capacity
Inspiratory Capacity
Oxygen Cost of Hyperpnea (slope = mls of O2 used for each L of ventilation)
Resting end-expiratory diaphragm thickness (contralateral to the Malignant Pleural Effusion)

Linear mixed model will compare repeated measures between the two interventions:
MIP
Dyspnea-12
EQ-5D-5L

Cox proportional hazard modelling will compare the proportion of patients (a) requiring further invasive drainage of effusion, or (b) with pneumonia, over the 6 month period from randomization

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/08/2015
Actual
Date of last participant enrolment
Anticipated
26/02/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4093 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 4094 0
The Wesley Hospital - Auchenflower
Recruitment hospital [3] 4095 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 4096 0
St Andrew's War Memorial Hospital - Brisbane
Recruitment postcode(s) [1] 10023 0
4032 - Chermside
Recruitment postcode(s) [2] 10024 0
4066 - Auchenflower
Recruitment postcode(s) [3] 10025 0
4006 - Herston
Recruitment postcode(s) [4] 10026 0
4001 - Brisbane

Funding & Sponsors
Funding source category [1] 291712 0
University
Name [1] 291712 0
Queensland University of Technology
Country [1] 291712 0
Australia
Primary sponsor type
Individual
Name
Dr Luke Garske
Address
Institute of Health and Biomedical Innovation
Queensland University of Technology
60 Musk Ave
Kelvin Grove QLD 4059, Australia
Country
Australia
Secondary sponsor category [1] 290387 0
Individual
Name [1] 290387 0
Associate Professor Ian Stewart
Address [1] 290387 0
Program Leader – Environmental Health, Institute of Health and Biomedical Innovation
Queensland University of Technology
60 Musk Ave
Kelvin Grove QLD 4059 Australia
Country [1] 290387 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293234 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 293234 0
Ethics committee country [1] 293234 0
Australia
Date submitted for ethics approval [1] 293234 0
Approval date [1] 293234 0
09/07/2015
Ethics approval number [1] 293234 0
HREC/15/QPCH/159
Ethics committee name [2] 293235 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [2] 293235 0
Ethics committee country [2] 293235 0
Australia
Date submitted for ethics approval [2] 293235 0
Approval date [2] 293235 0
07/07/2015
Ethics approval number [2] 293235 0
1517

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

Contacts
Principal investigator
Name 58998 0
Dr Luke Garske
Address 58998 0
PhD Candidate, Thoracic and Sleep Physician
Institute of Health and Biomedical Innovation, Queensland University of Technology
60 Musk Ave
Kelvin Grove QLD 4059, Australia
Country 58998 0
Australia
Phone 58998 0
+61, 7, 3138 6089
Fax 58998 0
Email 58998 0
luke.garske@connect.qut.edu.au
Contact person for public queries
Name 58999 0
Luke Garske
Address 58999 0
PhD Candidate, Thoracic and Sleep Physician
Institute of Health and Biomedical Innovation, Queensland University of Technology
60 Musk Ave
Kelvin Grove QLD 4059, Australia
Country 58999 0
Australia
Phone 58999 0
+61, 7, 3138 6089
Fax 58999 0
Email 58999 0
luke.garske@connect.qut.edu.au
Contact person for scientific queries
Name 59000 0
Luke Garske
Address 59000 0
PhD Candidate, Thoracic and Sleep Physician
Institute of Health and Biomedical Innovation, Queensland University of Technology
60 Musk Ave
Kelvin Grove QLD 4059, Australia
Country 59000 0
Australia
Phone 59000 0
+61, 7, 3138 6089
Fax 59000 0
Email 59000 0
luke.garske@connect.qut.edu.au

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

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