Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001371583
Ethics application status
Approved
Date submitted
11/12/2015
Date registered
16/12/2015
Date last updated
18/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Lung Ultrasound STudy - Diaphragm dysfunction after lung transplant
Scientific title
Using point-of-care ultrasound to report the incidence of diaphragm dysfunction after lung transplant: A longitudinal cohort study.
Secondary ID [1] 288054 0
Nil known
Universal Trial Number (UTN)
Trial acronym
LUST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung transplant 296923 0
Diaphragm dysfunction 296924 0
Diaphragm atrophy 296925 0
Condition category
Condition code
Respiratory 297166 297166 0 0
Other respiratory disorders / diseases
Surgery 297292 297292 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Diaphragmatic dysfunction (DD) represents an important clinical problem after lung transplant and has a considerable influence on respiratory function and recovery. It frequently results in longer duration of mechanical ventilation; ICU and hospital stay which as a result may lead to further deconditioning. The incidence of diaphragmatic dysfunction following lung transplant surgery has been estimated at greater than 40 per cent. However, to date, its incidence has only been documented retrospectively using EMG techniques (Ferdinande, Bruyninckx, Van Raemdonck, Daenen, & Verleden, 2004). There is little documentation in the literature regarding the natural history and prognosis of diaphragmatic dysfunction in these patients.
Ultrasound has been used to identify severe diaphragmatic dysfunction post cardiac surgery (Lerolle et al., 2009). Bedside ultrasound by Intensivists has been shown to be as accurate as fluoroscopy for diaphragmatic dysfunction in patients post cardiac surgery (Sanchez de Toledo et al., 2010). This assessment can be performed at the bedside and avoids the exposure to radiation.

By documenting the incidence and extent of this problem, we hope to identify risk factors for developing DD and determine if any of these are preventable with future studies.

Methods:
Ultrasonographic examinations will be performed in the semirecumbent, 45 degree head up position. Measurements will be taken to assess diaphragm excursion (descent) and diaphragm thickening.

For Excursion:
Two-dimensional mode will be used to find the best approach and to select the exploration line of each hemidiaphragm. The liver will be used as a window on the right while the spleen will be used on the left hemidiaphragm. All examinations will be recorded on a computer for subsequent blind analysis. A subcostal or low intercostal probe position will be chosen between the anterior and mid axillary lines to obtain the best imaging of the left hemidiaphragmatic dome. The motion will be recorded during the same respiratory maneuvers as for the right hemidiaphragm.
The diaphragm inspiratory amplitudes (excursions) will be measured from the M-mode sonography. For the Quiet Breathing and Deep Breathing measurements, the first caliper will be placed at the foot of the inspiration slope on the diaphragm echoic line and the second caliper will be placed at the apex of this slope. For Voluntary Sniff measurement, the amplitude of excursion will be measured on the vertical axis of the tracing from the baseline to the point of maximum height of inspiration on the graph. Several respiratory cycles will be recorded, and measurements will be averaged from at least three different cycles. Presence of ultrasonographic diaphragmatic dysfunction will be defined by diaphragmatic excursion of less than 10mm (Boussuges, Gole, & Blanc, 2009; Kim, Suh, Hong, Koh, & Lim, 2011). The treating team will be notified within 24hours if diaphragmatic dysfunction is identified.

For Thickening:
A linear transducer will be placed between the eighth and ninth intercostal space, between the anterior and medial axillary lines. Measurements of diaphragm thickness will be taken in B-mode at end-inspitation and end-expiration during normal spontaneous breathing. An average will be calculated from three independent breaths. Thickening fraction will be calculated as Thickness at End-inspiration minus Thickness at End expiration; divided by thickness at End-expiration (Matamis et al, 2013).
Diaphragmatic thickening fraction can be used as an index of diaphragmatic efficiency as a pressure generator (Vivier et al, 2012)

Each examination will be conducted by the physiotherapist or physician and will take approximately 15-20 minutes to complete at each time-point ie. pre-op, Day 1, Week 1, Month 1 and Month 3. To complete all five examinations we estimate it will require a total of 75 minutes per participant.
Intervention code [1] 293378 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296805 0
To document the incidence of diaphragmatic dysfunction (DD) in lung transplant patients post-operatively using point of care ultrasound by intensive care and respiratory physicians and physiotherapists.
Timepoint [1] 296805 0
Pre-operative assessment, and assessments one day, one week, one month and three months post-operatively.
Secondary outcome [1] 319401 0
To study the evolution of diaphragmatic function over time, up to 3 months post-operatively using point of care ultrasound by intensive care physiotherapists and/or physicians. Measures of diaphragmatic excursion and thickness will be compared at each time interval.
Timepoint [1] 319401 0
Comparison of images taken at one day, one week, one month and three months post-operatively.
Secondary outcome [2] 319402 0
To identify pre, intra and post-operative risk factors that contribute to diaphragm dysfunction such as age, gender, duration of mechanical ventilation and indication for transplant. Risk factors will be identified by reviewing the patient's ICU and hospital medical records. Each potential risk factor for DD will be evaluated in a univariate model (with appropriate tests for continuous variables depdendent upon distribution and categorical variables depdendent on size) and then a multi-variate analysis will be performed.
Timepoint [2] 319402 0
From data analysis at completion of the study. Recruitment and study period 12 months.
Secondary outcome [3] 319403 0
Demonstrate inter and intra-rater reliability of diaphragmatic ultrasound
Timepoint [3] 319403 0
Prior to commencing subject recruitment - approximately one week duration.

Eligibility
Key inclusion criteria
Living within NSW, or able to attend the St Vincent's Heart & Lung Clinic.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Currently on mandatory mode of mechanical ventilation
* Known diaphragmatic dysfunction from another aetiology
* Unable to maintain position required for optimum imaging.
* Body habitus prevents adequate imaging
* History of previous lung transplant

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is an observational cohort study with descriptive variables. A sample size of 25 has been selected based on an expected incidence of 40 per cent to enable the evaluation of approximately 10 patients with diaphragmatic dysfunction.
Patients with DD will be compared to those without DD for relevant baseline variables, intra-operative features and post-operative variables. Continuous variables will be compared using Mann Whitney U test and discrete variables using chi-square test.
Continuous parameters related to serial diaphragmatic function in the same patient will be compared using analysis of variance (ANOVA).
Inter-observer variability will be measured using kappa statistic.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/01/2016
Actual
15/02/2016
Date of last participant enrolment
Anticipated
1/12/2016
Actual
12/12/2017
Date of last data collection
Anticipated
Actual
24/04/2018
Sample size
Target
25
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4860 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 12367 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 292517 0
Hospital
Name [1] 292517 0
St Vincent's Hospital
Country [1] 292517 0
Australia
Funding source category [2] 299513 0
Charities/Societies/Foundations
Name [2] 299513 0
St Vincent's Clinic Foundation
Country [2] 299513 0
Australia
Funding source category [3] 299514 0
Charities/Societies/Foundations
Name [3] 299514 0
St Vincent's Curran Foundation
Country [3] 299514 0
Australia
Primary sponsor type
Individual
Name
Professor Allan Glanville
Address
St Vincent's Heart and Lung Clinic
St Vincent's Hospital
390 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 291283 0
None
Name [1] 291283 0
Address [1] 291283 0
Country [1] 291283 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293991 0
St Vincent's Hospital Sydney HREC
Ethics committee address [1] 293991 0
St Vincent's Hospital Research Office
Level 6 de Lacy Building
390 Victoria St
Darlinghurst NSW 2010
Ethics committee country [1] 293991 0
Australia
Date submitted for ethics approval [1] 293991 0
07/10/2014
Approval date [1] 293991 0
06/11/2014
Ethics approval number [1] 293991 0
HREC/14/SVH/203

Summary
Brief summary
Diaphragmatic dysfunction (DD) represents an important clinical problem after lung transplant and has a considerable influence on respiratory function and recovery. It frequently results in longer time on the ventilator; longer time in Intensive Care and longer time in hospital, which as a result may lead to further muscle weakness. The incidence of diaphragmatic dysfunction following lung transplant surgery has been estimated at more than 40 per cent. There is little documentation in the literature regarding the natural history and prognosis of diaphragmatic dysfunction in these patients.
Ultrasound has been used to identify severe diaphragmatic dysfunction after heart surgery (Lerolle et al., 2009). Bedside ultrasound has been shown to be accurate for the assessment of diaphragmatic dysfunction in patients after heart surgery (Sanchez de Toledo et al., 2010). This assessment can be performed at the bedside and avoids the exposure to radiation.

By documenting the incidence and extent of this problem, we hope to identify risk factors for diaphragm dysfunction and determine if any of these are preventable with future studies.

Patients will be identified from the active lung transplant waiting list and approached for enrolment when they attend their routine heart-lung clinic appointments, or scheduled assessments. Protocolised diaphragm ultrasound assessments will occur whilst on active list, in Intensive Care on day 1 after transplant, in hospital in week 1, in hospital/heart-lung clinic at one month and three months post lung transplant.

Measurements of diaphragm excursion (descent) and thickness will be taken at each assessment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61934 0
Dr Sean Scott
Address 61934 0
St Vincent's Hospital
390 Victoria St
Darlinghurst NSW 2010
Country 61934 0
Australia
Phone 61934 0
+61 2 8382 2514
Fax 61934 0
Email 61934 0
[email protected]
Contact person for public queries
Name 61935 0
Ms Elise Crothers
Address 61935 0
St Vincent's Hospital
390 Victoria St
Darlinghurst NSW 2010
Country 61935 0
Australia
Phone 61935 0
+61 2 8382 2265
Fax 61935 0
Email 61935 0
[email protected]
Contact person for scientific queries
Name 61936 0
Dr Sean Scott
Address 61936 0
St Vincent's Hospital
390 Victoria St
Darlinghurst NSW 2010
Country 61936 0
Australia
Phone 61936 0
+61 2 8382 2514
Fax 61936 0
Email 61936 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



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