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Trial registered on ANZCTR
Registration number
ACTRN12624001130550
Ethics application status
Approved
Date submitted
28/08/2024
Date registered
18/09/2024
Date last updated
29/09/2024
Date data sharing statement initially provided
18/09/2024
Type of registration
Prospectively registered
Titles & IDs
Public title
An implementation-effectiveness trial to evaluate physiotherapy guideline care in practice and determine whether a course of protocolised physiotherapy ventilator lung hyperinflation treatment, added to guideline care, is feasible, safe, cost-effective and improves patient-important outcomes for ICU patients with severe pneumonia requiring invasive mechanical ventilation.
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Scientific title
An implementation-effectiveness trial investigating feasibility, safety and efficacy of Best pRacticE guideline cAre physioTHErapy with addition of protocolised ventilator hyperinflation on patient-important outcomes for critically ill adults intUbated and ventilated with Pneumonia. (BREATHE UP)
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Secondary ID [1]
311508
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None
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Universal Trial Number (UTN)
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Trial acronym
Breathe Up
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
pneumonia
332845
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Condition category
Condition code
Respiratory
329560
329560
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0
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Other respiratory disorders / diseases
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Physical Medicine / Rehabilitation
329561
329561
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0
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Physiotherapy
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Guideline physiotherapy care according to van der Lee et al (2024) incorporating a modified ventilator hyperinflation (VHI) treatment by Jacob et al 2021, performed by ICU physiotherapists, at a set daily dosage and frequency of 3 times per day. The VHI technique described by Jacob et al (2021) is based on the individual patient’s estimated inspiratory reserve volume (IRV), to determine the target increase in tidal volume above resting tidal volume which would be safe to deliver to the patient via the ventilator to simulate a deep breath, for the purpose of recruiting atelectatic alveoli via collateral channels to mobilise sputum which can then be cleared via airway suctioning. The following formulae will be used to calculate the estimated IRV as per Jacob et al (2021), using Microsoft Excel, based on each patient’s age, height and weight up to a Body Mass Index (BMI) of 25. Predicted body weight (BMI 25) was used for patients who were overweight or obese.
Estimated IRV (male) =2.89 x height + 0.016 x age - 0.032 x weight - 12.69
Estimated IRV (female) = 1.72 × height - 0.016 x age - 0.022 x weight - 4.91
Patients who are randomised to receive the new VHI treatment will receive four sets of eight to ten breaths, three times per day until extubation or Day 28 in ICU, whichever occurs first. The patient will receive eight to ten breaths per cycle to minimise hyperventilation. An inspiratory time of 3-5 seconds will be used.
In this study, the determined target hyperinflation volume will be limited at a peak pressure of 40cmH2O, which multiple studies have shown to be both effective and safe. Peak pressure is monitored continuously on the ventilator display and reviewed by treating clinicians.
The VHI treatment will be delivered via the patient’s mechanical ventilator using a volume-controlled mode with a decelerating flow pattern, which is pressure limited, with alarms set accordingly to allow the delivery of the treatment VHI breath set to a maximum inspiratory pressure of 40 cmH2O. For patients who have progressed to breathing spontaneously on the ventilator without the need for mandatory ventilator breaths, or who have difficulty with ventilator synchrony, the VHI treatment may be performed using a pressure-support mode of ventilation, where all breaths are triggered by the patient and pressure support is provided to deliver the target volume by the ventilator above the patient’s own breathing effort, up to a pressure limit of 40cmH2O. Research has shown this to be an effective and safe method of delivering VHI treatment in this context and improves patient-ventilator synchrony in patients who are weaning.
Data will be collected at the bedside by the treating clinician regarding each episode of treatment delivered, including the time of treatments, dosage delivered (number of sets and repetitions of breaths), ventilator parameters during treatment, and target and achieved tidal volumes and inspiratory pressures in order to evaluate treatment adherence and fidelity.
Active respiratory physiotherapy treatment, comprising deep breathing exercises and coughing, will be performed daily at a minimum, between extubation and ICU discharge as per guideline care. Once awake and able to participate actively in rehabilitation, muscle strengthening and early mobilisation will be standardised to 20 minutes per day between groups and based on patient’s highest level of function according to the ICU Mobility Scale (IMS).
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Intervention code [1]
327963
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Treatment: Other
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Intervention code [2]
327964
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Rehabilitation
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Comparator / control treatment
Guideline physiotherapy care according to van der Lee et al (2024) incorporating varied treatment modes which may include manual hyperinflation using a manual resuscitation bag or conservative VHI using the ventilator, delivered at a variable daily dosage according to the discretion of the treating physiotherapist until extubation.
Active respiratory physiotherapy treatment, comprising deep breathing exercises and coughing, will be performed daily at a minimum, between extubation and ICU discharge as per guideline care. Once awake and able to participate actively in rehabilitation, muscle strengthening and early mobilisation will be standardised to 20 minutes per day between groups, and based on patient’s highest level of function according to the ICU Mobility Scale (IMS).
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Control group
Active
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Outcomes
Primary outcome [1]
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- Disability
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Assessment method [1]
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WHODAS 2.0
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Timepoint [1]
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Day 90 post randomisation.
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Secondary outcome [1]
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Feasibility
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Assessment method [1]
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These will be assessed as composite outcomes:
- Patient recruitability, determined from study logs
- Patient treatability (treatable traits), determined from daily data collection
- Treatment fidelity of new VHI (Rx arm), determined from physiotherapy data collection
- Group separation, determined by statistical anlaysis at 50% data collection
- Physiotherapy compliance with guideline care, determined by daily data collection
- Barriers to guideline care, determined by daily data collection
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Timepoint [1]
439133
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3 years post study commencement.
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Secondary outcome [2]
439134
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Safety
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Assessment method [2]
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These will be assessed as a composite outcome.
- Inflammatory biomarkers (CRP and WBC count)
- Occurrence of predefined adverse events (AE) & serious adverse events (SAE)s
The following are examples of possible adverse events, which will be assessed at the point of care by clinical examination:
Hypotension with MAP < 60, or 5mmHg below the physiological target set by the treating intensivist, for greater than 2 minutes or requiring remedial correction with vasopressors during or within 30 minutes of respiratory physiotherapy
- Hypertension with SBP > 180mmHg for greater than 2 minutes or requiring medical attention during or within 30 minutes of respiratory physiotherapy
- SpO2 < 85% for greater than 2 minutes, during or within 30 minutes of respiratory physiotherapy
- Haemodynamically significant change in heart rhythm (e.g. bradycardia, ventricular ectopy or rapid atrial fibrillation with blood pressure compromise) during or within 30 minutes of respiratory physiotherapy.
The following are examples of possible (although unlikely) serious adverse events, which will be assessed at the point of care by clinical examination:
- Unplanned extubation during or immediately after respiratory physiotherapy treatment
- Pneumothorax during or 30 minutes following intervention requiring drainage, confirmed by radiologist’s report
- Serious cardiac arrythmia during or within 30 minutes or respiratory physiotherapy e.g. sustained SVT, VT or VF.
- Cardiac arrest during or within 30 minutes of respiratory physiotherapy
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Timepoint [2]
439134
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- Safety will be assessed by a data safety monitoring board (DSMB) at 50% recruitment regarding occurrence of AEs and SAEs
- Inflammatory biomarkers will be assessed at baseline, and Day 7 or ICU discharge.
All AEs and SAEs will be assessed up to 28 days post randomisation.
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Secondary outcome [3]
439135
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- Ventilator free days
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Assessment method [3]
439135
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Counting number of days that patient is free from requiring mechanical ventilation up to Day 28. This will be determined from review of medical records.
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Timepoint [3]
439135
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Day 28 post randomisation.
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Secondary outcome [4]
439136
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Antibiotic free days
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Assessment method [4]
439136
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Counting number of days that patient is free from antibiotic therapy at Day 28 post randomisation from review of medical records.
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Timepoint [4]
439136
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At day 28 post randomisation
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Secondary outcome [5]
439137
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Vasopressor free days.
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Assessment method [5]
439137
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Counting number of days that patient is free from requiring vasopressor support at Day 28 post randomisation by review of medical records.
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Timepoint [5]
439137
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At day 28 post randomisation.
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Secondary outcome [6]
439138
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Discharge destination.
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Assessment method [6]
439138
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From medical record
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Timepoint [6]
439138
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at hospital discharge.
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Secondary outcome [7]
439139
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Mortality
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Assessment method [7]
439139
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From hospital records
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Timepoint [7]
439139
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At day 28 post randomisation and day 90 post randomisation.
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Secondary outcome [8]
439140
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Days alive and out of hospital
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Assessment method [8]
439140
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Counting number of days that patient is alive and out of hospital at day 90 post randomisation.
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Timepoint [8]
439140
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Day 90 post randomisation.
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Secondary outcome [9]
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Health-related quality of life
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Assessment method [9]
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EQ-5D-5L Australian version by phone follow-up.
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Timepoint [9]
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Day 90 post randomisation.
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Secondary outcome [10]
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Multidisciplinary staff satisfaction with physiotherapy guideline care.
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Assessment method [10]
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May be explored as a sub study using focus groups or questionnaire which will be specifically designed for this study.
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Timepoint [10]
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By end of study.
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Eligibility
Key inclusion criteria
• ICU admission with diagnosis of pneumonia made by a medical practitioner.
• Aged equal to or greater than 18 years
• Intubated and mechanically ventilated, expected to remain so for equal to or greater than 24 hours, not planned for extubation this calendar day.
• Evidence of consolidation or volume loss on CXR, CT scan or lung ultrasound.
• Evidence of sputum on clinical assessment by a physiotherapist, e.g. auscultation, palpation, endotracheal suction, waveform analysis.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
• Death imminent or the treating clinician believes that death during this hospital admission is inevitable.
• Treating clinician believes that trial participation is not in the best interests of the patient.
• Receiving invasive mechanical ventilation for greater than 5 days
• Peak airway pressure greater than 35cmH20 consistently for greater than 2 hours
• Progression to severe ARDS according to Berlin Criteria [32]
• Requirement for extracorporeal membrane oxygenation
• Severe bronchospasm
• Undrained pneumothorax or bronchopleural fistula
• Pulmonary haemorrhage
• Lung transplantation or recent lung surgery with bronchial resection
• Unable to communicate in English
• Pregnancy
• Underlying neurological or myopathic condition
• Documented cognitive impairment
• BMI greater than 35
• Hospitalisation for greater than 7 days prior to ICU
• Presence of active cancer or active use of chemotherapeutic agents or neutropenia
• Unlikely to be available for 3-month follow-up (resides overseas)
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Computerised randomisation using REDCap with allocation concealment.
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1:1 block randomisation with stratification according to site.
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Not Applicable
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Type of endpoint/s
Safety/efficacy
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Statistical methods / analysis
Descriptive statistics will consist of means and standard deviations, or medians and interquartile ranges for continuous data, and frequency distributions for categorical data. Univariate group comparisons will be done using independent t-tests or non-parametric Mann-Whitney U tests for continuous data & Chi-squared or Fisher’s Exact tests for categorical data. Mixed effects generalised linear models, including random effects for patients and site, will be used to examine longitudinal (discharge and 3-months) primary outcome WHODAS 2.0 and secondary outcomes EQ5D-5L and Borg Dyspnoea score. Results will be summarised using estimated mean differences and 95% confidence intervals (CI). Mixed effects logistic regression models will be used to examine longitudinal mortality outcomes, with results summarised using odds ratios (OR) and 95%CI. Ventilator free days will be described using negative binomial models and summarised using estimated means and 95%CIs. Length of stay outcomes will be examined using Kaplan-Meier survival probabilities and described using median (95%CI) days duration, with Log Rank tests used for group comparisons. Cox regression models may be used to derive hazard ratios (HR). Quality-adjusted life years (QALYS) will be calculated using utility scores from the EQ-5D-5L collected at 3-months post randomisation. An a priori subgroup analysis according to site is planned to investigate any between group difference that is site specific. An interim analysis is planned at 50% recruitment to investigate safety and treatment effect on the primary outcome. Data will be analysed using Stata 18.0 (StataCorp LLC, College Station, TX).
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
1/10/2024
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Actual
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
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Sample size
Target
225
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
27034
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Fiona Stanley Hospital - Murdoch
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Recruitment hospital [2]
27035
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Sir Charles Gairdner Hospital - Nedlands
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Recruitment postcode(s) [1]
43103
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6150 - Murdoch
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Recruitment postcode(s) [2]
43104
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6009 - Nedlands
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Funding & Sponsors
Funding source category [1]
315799
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Charities/Societies/Foundations
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Name [1]
315799
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Raine Medical Research Foundation
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Address [1]
315799
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Country [1]
315799
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Australia
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Funding source category [2]
317280
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Government body
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Name [2]
317280
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Future Health Research and Innovation Fund
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Address [2]
317280
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Country [2]
317280
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Australia
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Primary sponsor type
Hospital
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Name
South Metropolitan Health Service
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Address
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Country
Australia
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Secondary sponsor category [1]
319558
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Hospital
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Name [1]
319558
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North Metropolitan Health Service
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Address [1]
319558
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Country [1]
319558
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Australia
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Other collaborator category [1]
283162
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University
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Name [1]
283162
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The University of Western Australia
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Address [1]
283162
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Country [1]
283162
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Australia
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Other collaborator category [2]
283163
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University
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Name [2]
283163
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The University of Melbourne
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Address [2]
283163
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Country [2]
283163
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Australia
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Other collaborator category [3]
283164
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University
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Name [3]
283164
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The Chinese University of Hong Kong
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Address [3]
283164
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Country [3]
283164
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Hong Kong
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
314656
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South Metropolitan Health Service Human Research Ethics Committee
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Ethics committee address [1]
314656
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https://smhs.health.wa.gov.au/Our-research/For-researchers
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Ethics committee country [1]
314656
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Australia
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Date submitted for ethics approval [1]
314656
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26/04/2024
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Approval date [1]
314656
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24/07/2024
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Ethics approval number [1]
314656
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Summary
Brief summary
The aims of this study are: 1. To determine the feasibility (acceptability and fidelity) of implementing the physiotherapy guideline in patients with pneumonia, incorporating a set dosage of ventilator hyperinflation (VHI) treatment, with target volume determined for each patient according to their estimated inspiratory reserve volume, based on height as per Jacob et al (2021). 2. To explore pneumonia phenotypes which demonstrate treatable traits that are amenable to respiratory physiotherapy intervention commenced during the acute period of invasive mechanical ventilation. 3. To determine the effect of a course of VHI treatment method], at a set dosage and frequency of three times daily for the duration of the period that patients are on the mechanical ventilator on symptomatology and patient-centred outcomes. 4. To determine the cost-effectiveness of physiotherapy guideline care incorporating a course of new VHI treatment for pneumonia requiring invasive ventilation in ICU. It is hypothesised that best practice physiotherapy guideline care, with incorporation of protocolised VHI treatment is safe, feasible and effective in improving patient-important outcomes for critically ill adults requiring invasive mechanical ventilation for pneumonia.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Dr Lisa van der Lee
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Address
132306
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Fiona Stanley Hospital, Robin Warren Drive Murdoch, 6150, Western Australlia
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Country
132306
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Australia
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Phone
132306
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+61 08 6152 6547
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Fax
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Email
132306
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[email protected]
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Contact person for public queries
Name
132307
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Lisa van der Lee
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Address
132307
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Fiona Stanley Hospital, Robin Warren Drive Murdoch, 6150, Western Australlia
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Country
132307
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Australia
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Phone
132307
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+61 08 6152 6547
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Fax
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Email
132307
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[email protected]
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Contact person for scientific queries
Name
132308
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Lisa van der Lee
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Address
132308
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Fiona Stanley Hospital, Robin Warren Drive Murdoch, 6150, Western Australlia
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Country
132308
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Australia
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Phone
132308
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+61 08 6152 6547
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Fax
132308
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Email
132308
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
de-identified participant data may be shared with a data transfer agreement.
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When will data be available (start and end dates)?
Available following publication with no end date.
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Available to whom?
Only researchers who provide a methodologically sound proposal.
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Available for what types of analyses?
IDP meta-analyses
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How or where can data be obtained?
Subject to approvals by the chief principal investigator.
Email contact:
[email protected]
.
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
No additional documents have been identified.
Download to PDF