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Trial registered on ANZCTR


Registration number
ACTRN12619000889156p
Ethics application status
Submitted, not yet approved
Date submitted
14/06/2019
Date registered
26/06/2019
Date last updated
14/11/2019
Date data sharing statement initially provided
26/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Accelerating ventilator weaning in spinal cord injury with non-invasive Abdominal Stimulation
Scientific title
Accelerating ventilator weaning in spinal cord injury with non-invasive Abdominal Stimulation
Secondary ID [1] 298500 0
None
Universal Trial Number (UTN)
U1111-1235-3414
Trial acronym
Linked study record
ACTRN12618000214235 uses the same protocol but specifically excludes patients dependent on mechanical ventilation. By including mechanically ventilated patients in this sister study, we greatly improve the efficiency of both trials.

Health condition
Health condition(s) or problem(s) studied:
spinal cord injury 313286 0
tetraplegia 313352 0
paralysis 313353 0
Condition category
Condition code
Neurological 311732 311732 0 0
Other neurological disorders
Physical Medicine / Rehabilitation 311733 311733 0 0
Other physical medicine / rehabilitation
Injuries and Accidents 311734 311734 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The abdominal muscles are the primary muscle group used during forced exhalation. We have shown that surface Functional Electrical Stimulation (FES) of the abdominal muscles, termed Abdominal FES, can improve respiratory function and may assist weaning from mechanical ventilation in spinal cord injury. However, the effect of Abdominal FES on mechanical ventilation duration has yet to be studied in a fully powered trial. We hypothesise that Abdominal FES will reduce mechanical ventilation duration after spinal cord injury.

One hundred and forty eight participants will be recruited to this multi-site randomised, placebo controlled pilot trial. Participants with a new cervical spinal cord injury will be recruited 5-10 days post injury. 74 patients will be randomly allocated to receive Abdominal FES and 74 will receive a placebo. In the Abdominal FES group, Abdominal FES will be applied for 45 minutes per day, 5 days per week, for 8 weeks. Adherence will be monitored using a daily training diary.

Specifically, Abdominal FES will be delivered, via electrodes placed over the posterolateral surface of the abdomen. The stimulation amplitude will initially be set to 60 mA (50 Hz), which corresponds to 90% of the maximum amplitude that was tolerated by healthy volunteers in a previous study. If this amplitude results in discomfort to the patient (based on clinical judgement) then it will be reduced as necessary.Stimulation amplitude will be evaluated every 5 minutes to ensure that stimulation is still tolerable and causing a suitable muscle contraction. Stimulation will be applied by a local physiotherapist at each site.
Intervention code [1] 314750 0
Treatment: Devices
Intervention code [2] 314783 0
Rehabilitation
Comparator / control treatment
Participants in the placebo group will receive sham Abdominal FES for 45 minutes per day, five days per week, for 8 weeks. Placebo Abdominal FES will be similar to active FES in all respects except for the simulation intensity, which will be kept to a level which does not cause a muscle contraction.

Specifically, stimulation pulses will be delivered at a frequency of 10 Hz and at a low current amplitude (< 10 mA) that does not cause abdominal muscle contraction. These settings were chosen so that participants experience the sensation of Abdominal FES without an abdominal muscle contraction. The placebo will be applied by a local physiotherapist at each site.
Control group
Placebo

Outcomes
Primary outcome [1] 320422 0
Mechanical Ventilation Duration recorded from medical records
Timepoint [1] 320422 0
Mechanical ventilation duration after spinal cord injury (note participants will be censored if they are still ventilated 17 weeks post injury)
Secondary outcome [1] 371530 0
Forced Vital Capacity, measured using spirometry
Timepoint [1] 371530 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [2] 371531 0
Forced Expiratory Volume in one Second, measured using spirometry
Timepoint [2] 371531 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [3] 371532 0
Peak Expiratory Flow, measured using spirometry
Timepoint [3] 371532 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [4] 371533 0
Maximum Inspiratory Pressure, measured using spirometry
Timepoint [4] 371533 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [5] 371534 0
Maximum Expiratory Pressure, measured using spirometry
Timepoint [5] 371534 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [6] 371535 0
Respiratory complications recorded from medical records (e.g. pneumonia, atelectasis)
Timepoint [6] 371535 0
9 and 17 weeks post injury
Secondary outcome [7] 371537 0
Quality of life measured using SF-36 QoL questionnaire
Timepoint [7] 371537 0
When the participant is able to breathe independently, nine and 17 weeks post injury.
Secondary outcome [8] 371538 0
Mortality, recorded from patient's medical record
Timepoint [8] 371538 0
17 weeks post injury

Eligibility
Key inclusion criteria
- 5-10 days post C3-C8 cervical spinal cord injury (i.e. tetraplegia)
- over 18 years of age
- mechanical ventilation dependence
- no useful abdominal muscle movement
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- American Spinal Injuries Association Impairment Scale D (patients have near normal respiratory muscle function and low risk of respiratory complications, making the intervention redundant)
- progressive neurological disease or chronic respiratory disease
- physical obstacles that prevent Abdominal FES (e.g. pregnancy, abdominal trauma, pacemaker)
- no response to Abdominal FES (e.g. lower motor neuron impairment)
- uncontrolled hypertension (placing the patient at risk of autonomic dysreflexia)

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)
Each participant will be randomly assigned to active or placebo Abdominal FES in a 1:1 ratio using a random, secure, web-based program (REDCap) by an independent investigator
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomised computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Participant variables will be presented using means and standard deviations for continuous normally distributed variables, medians and interquartile ranges for continuous non-normally distributed variables, and proportions and absolute numbers for categorical variables.

The primary outcome in this study is mechanical ventilation duration, with death before weaning from mechanical ventilation a competing event. Given an expected mortality rate of ~10%, and to avoid introducing bias due to participants who die while ventilated being unable to either wean from mechanical ventilation, the primary outcome (ventilation duration) will be analysed using competing risk survival analysis. Specifically, ventilation duration will be analysed using a Gray’s test, with the competing risks of death or withdrawal of treatment (e.g. ventilator support) with the intention of subsequent death. Respiratory complications will be analysed using a Chi-squared test to determine the effect of Abdominal FES on respiratory complications. The mean and median number of complications by group will be reported along as a measure of the spread according to the distribution. If the distribution allows, the number of complications will be analysed using negative binomial regression to estimate the difference in the number of complications between groups. The incidence rate ratio and its 95% CI will be reported. The model output will be examined to confirm that negative binomial regression is more appropriate than Poisson regression. If not, Poisson regression will be used. Days of follow-up will be included as an exposure term in these models. In the event of low variability in the number of respiratory complications the outcome may be categorised and multinomial logistic regression used. Generalized linear models will be used to compare respiratory function (as % predicted) and mortality between the intervention and sham groups. Health economic modelling from a health care provider perspective will be performed and involve cost utility analysis (using the SF-6D utility score), to estimate the cost-effectiveness of Abdominal FES.

Recruitment
Recruitment status
Not yet recruiting
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)
NSW,WA,VIC
Recruitment hospital [1] 14000 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 14001 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 15162 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 15163 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 26779 0
2031 - Randwick
Recruitment postcode(s) [2] 26780 0
2065 - St Leonards
Recruitment postcode(s) [3] 28463 0
3084 - Heidelberg
Recruitment postcode(s) [4] 28464 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 21605 0
United Kingdom
State/province [1] 21605 0
Glasgow, Scotland
Country [2] 21606 0
Thailand
State/province [2] 21606 0
Chaing Mai
Country [3] 21607 0
India
State/province [3] 21607 0
Delhi, Vellore
Country [4] 22114 0
New Zealand
State/province [4] 22114 0
Auckland
Country [5] 22115 0
Canada
State/province [5] 22115 0
Alberta, Hamilton

Funding & Sponsors
Funding source category [1] 303043 0
Government body
Name [1] 303043 0
National Health and Medical Research Council
Address [1] 303043 0
National Health and Medical Research Council GPO Box 1421 Canberra ACT 2601
Country [1] 303043 0
Australia
Funding source category [2] 303044 0
Charities/Societies/Foundations
Name [2] 303044 0
Wings for Life
Address [2] 303044 0
Fürstenallee 4 5020 Salzburg Austria
Country [2] 303044 0
Austria
Primary sponsor type
Other
Name
Neuroscience Research Australia
Address
139 Barker Street
Randwick
NSW 2031
Country
Australia
Secondary sponsor category [1] 303026 0
None
Name [1] 303026 0
Address [1] 303026 0
Country [1] 303026 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303595 0
South Eastern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 303595 0
Prince of Wales Hospital Barker Street Randwick NSW 2031
Ethics committee country [1] 303595 0
Australia
Date submitted for ethics approval [1] 303595 0
21/06/2019
Approval date [1] 303595 0
Ethics approval number [1] 303595 0

Summary
Brief summary
A spinal cord injury is a devastating event, with approximately 350 new cases in Australia every year. Each injury has a lifetime cost of >$5m. More than half of these injuries will be caused by an injury to the cervical (neck) area of the spinal cord, termed tetraplegia. While tetraplegia is commonly associated with paralysis of all four limbs, paralysis also affects the major respiratory muscles, namely the diaphragm, abdominal and intercostal muscles. This reduces respiratory function, with associated complications a leading cause of illness and death for people with tetraplegia. Poor respiratory function leads to approximately 40% of people with tetraplegia requiring mechanical ventilation in the early stage of injury. This increases the likelihood of illness and death, delays rehabilitation and hospital discharge and costs an additional $2,000 per patient per day. The application of electrical pulses to the abdominal muscles, called Abdominal Functional Electrical Stimulation (Abdominal FES) improves respiratory function in tetraplegia. We have shown that Abdominal FES is a feasible technique to assist ventilator weaning for this group. Despite these positive results, a lack of data from large trials has prevented Abdominal FES being adopted as a standard treatment. We propose an international randomised controlled trial to assess whether Abdominal FES reduces mechanical ventilation duration in people with tetraplegia. Such a reduction has the potential to improve the health and rehabilitation prospects of people with tetraplegia globally, and result in a significant cost saving for health care providers. The final outcome of this project will be the development of an Abdominal FES treatment
program, facilitating the successful translation of this research into worldwide clinical practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94198 0
Dr Euan McCaughey
Address 94198 0
Neuroscience Research Australia
139 Barker St
Randwick
NSW 2031
Country 94198 0
Australia
Phone 94198 0
+61293991827
Fax 94198 0
Email 94198 0
e.mccaughey@neura.edu.au
Contact person for public queries
Name 94199 0
Dr Euan McCaughey
Address 94199 0
Neuroscience Research Australia
139 Barker St
Randwick
NSW 2031
Country 94199 0
Australia
Phone 94199 0
+61293991827
Fax 94199 0
Email 94199 0
e.mccaughey@neura.edu.au
Contact person for scientific queries
Name 94200 0
Dr Euan McCaughey
Address 94200 0
Neuroscience Research Australia
139 Barker St
Randwick
NSW 2031
Country 94200 0
Australia
Phone 94200 0
+61293991827
Fax 94200 0
Email 94200 0
e.mccaughey@neura.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
all of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Upon publication, with no end limit
Available to whom?
anyone who wishes to access it
Available for what types of analyses?
any purpose
How or where can data be obtained?
Through supplementary information in open access publication
What supporting documents are/will be available?
No other documents available
Summary results
No Results