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Trial registered on ANZCTR


Registration number
ACTRN12617001180303
Ethics application status
Approved
Date submitted
9/08/2017
Date registered
11/08/2017
Date last updated
6/11/2019
Date data sharing statement initially provided
6/11/2019
Date results information initially provided
6/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Abdominal Functional Electrical Stimulation To Assist Ventilator Weaning In Critically Ill Patients
Scientific title
Abdominal Functional Electrical Stimulation To Assist Ventilator Weaning In Critically Ill Patients
Secondary ID [1] 292626 0
None
Universal Trial Number (UTN)
U1111-1200-4986
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 304320 0
Sepsis 304321 0
Traumatic Brain Injury 304322 0
Stroke 304323 0
Condition category
Condition code
Respiratory 303671 303671 0 0
Other respiratory disorders / diseases
Stroke 303672 303672 0 0
Haemorrhagic
Stroke 303673 303673 0 0
Ischaemic
Anaesthesiology 303674 303674 0 0
Anaesthetics
Physical Medicine / Rehabilitation 303675 303675 0 0
Other physical medicine / rehabilitation

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 assist weaning from mechanical ventilation in spinal cord injury. A pilot study of 11 ventilated critically ill patients found Abdominal FES maintained abdominal muscle thickness and decreased ventilation duration, however the sample size was too small to achieve statistical significance. We hypothesise that Abdominal FES in critically ill patients will reduce diaphragm and abdominal muscle atrophy, with the long term goal of this project to demonstrate reduced mechanical ventilation duration.

Twenty critically ill patients being treated in the Intensive Care Unit (ICU) of the Prince of Wales Hospital, Sydney, will be recruited to this randomised, placebo controlled pilot trial. Participants will be recruited who are mechanically ventilated and are expected to remain that way for at least 48 hours. Ten patients will be randomly allocated to receive Abdominal FES and 10 will receive a placebo. In the Abdominal FES group, Abdominal FES will be applied for 30 minutes, twice per day, 5 days per week, until the patient is discharged from the ICU.

Specifically, Abdominal FES will be delivered, via electrodes placed over the surface of the abdomen, at a frequency of 30 Hz and a pulse width of 350 µs. These settings are based on previous trials. The stimulation amplitude will initially be set to 60 mA, 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. In addition, the stimulation amplitude will be evaluated five and 20 minutes after the start of each session to ensure that stimulation is still tolerable and causing a suitable muscle contraction. Ultrasound will be used to verify whether stimulation results in a contraction of the abdominal muscles during the first Abdominal FES session.
Intervention code [1] 298849 0
Treatment: Devices
Comparator / control treatment
Participants in the placebo group will receive sham Abdominal FES for 30 minutes, twice per day, five days per week, until discharge from the intensive care unit. 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, a pulsewidth of 50 µs and at a low current amplitude that does not cause abdominal muscle contraction, verified with ultrasound. These settings were chosen so that participants experience the sensation of Abdominal FES without an abdominal muscle contraction. Initially, 10 mA of current will be applied and, if necessary, will be lowered in steps of 2 mA until no muscle contraction is seen with ultrasound.
Control group
Placebo

Outcomes
Primary outcome [1] 303036 0
Thickness of the abdominal muscles as measured by ultrasound
Timepoint [1] 303036 0
48 hours after initiation of mechanical ventilation compared to when breathing independently of mechanical ventilation for 24 hours
Primary outcome [2] 303051 0
Feasibility as measured by patient compliance, time needed to recruit patients, time needed to collect data, proportion of eligible patients of total ICU population, withdrawal rate and effectiveness of blinding
Timepoint [2] 303051 0
Final day of patient enrolment
Secondary outcome [1] 337731 0
Thickness of the diaphragm as measured by ultrasound
Timepoint [1] 337731 0
48 hours after initiation of mechanical ventilation compared to when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [2] 337732 0
Echogenicity of the abdominal wall muscles as measured by ultrasound
Timepoint [2] 337732 0
48 hours after initiation of mechanical ventilation compared to when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [3] 337733 0
Maximum expiratory pressure (MEP) measured using spirometry
Timepoint [3] 337733 0
when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [4] 337734 0
Maximum inspiratory pressure measured using spirometry
Timepoint [4] 337734 0
when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [5] 337735 0
Peak expiratory flow measured using spirometry
Timepoint [5] 337735 0
when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [6] 337736 0
Vital capacity measured using spirometry
Timepoint [6] 337736 0
when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [7] 337737 0
Time spent dependent on mechanical ventilation
Timepoint [7] 337737 0
when breathing independently of mechanical ventilation for 24 hours
Secondary outcome [8] 337738 0
Systemic inflammatory markers (IL-6, IL-1, IL-8) as measured by blood test
Timepoint [8] 337738 0
48 hours after initiation of mechanical ventilation compared to after 3 days of Abdominal FES
Secondary outcome [9] 337739 0
Time in Intensive Care Unit (ICU)
Timepoint [9] 337739 0
At ICU discharge
Secondary outcome [10] 337740 0
Number of Re-intubations in intensive care
Timepoint [10] 337740 0
Discharge from Intensive Care Unit
Secondary outcome [11] 337741 0
Quality of Life during and after mechanical ventilation as measured by SF-36 questionnaire
Timepoint [11] 337741 0
24 hours after extubation and at ICU discharge

Eligibility
Key inclusion criteria
mechanical ventilation dependence due to critical illness
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
pregnancy
expected to be ventilated for < 24 hours (based on clinical judgement)
ventilated for > 72 hours (to avoid excessive muscle atrophy)
non-pharmacological paralysis (e.g. spinal cord injury or Guillain-Barré syndrome)
physical obstacles that prevent Abdominal FES (e.g. severe abdominal trauma, pacemaker)
terminal illness
no response to Abdominal FES (e.g. lower motor neuron impairment)
recent abdominal surgery within four weeks prior to study inclusion
no clearly visible separate layers of the abdominal muscles (external oblique, internal oblique and transverse abdominal muscles), assessed with ultrasound during routine care

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 (SecureTrial) 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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Study results will first undergo descriptive level statistical analyses. For continuous variables, Two-way, Student’s t-tests will then be carried out using unequal variances where the variables are normally distributed. Tests for normality will be carried out using the Shapiro-Wilk method. Variables that are not normal in distribution that also cannot be log transformed to a normal distribution curve will be analysed using the Mann-Whitney U test or other non-parametric methods to be determined based on actual data distributions. For repeated measures, analysis of variance will be considered where methodologically appropriate.

Recruitment
Recruitment status
Completed
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
Recruitment hospital [1] 8750 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 16870 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 297255 0
Commercial sector/Industry
Name [1] 297255 0
Liberate Medical LLC
Address [1] 297255 0
6400 Westwind Way, Suite A
Crestwood, KY 40014
Country [1] 297255 0
United States of America
Funding source category [2] 297256 0
Other
Name [2] 297256 0
Australian Academy of Technology and Engineering
Address [2] 297256 0
Level 1 / 1 Bowen Crescent, Melbourne Vic 3004
Country [2] 297256 0
Australia
Primary sponsor type
Other
Name
Neuroscience Research Australia
Address
139 Barker Street
Randwick
NSW 2031
Country
Australia
Secondary sponsor category [1] 296227 0
None
Name [1] 296227 0
Address [1] 296227 0
Country [1] 296227 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298374 0
South Eastern Sydney Local Health District Human Research Ethics Committe
Ethics committee address [1] 298374 0
Research Support Office
G71, East Wing
Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 298374 0
Australia
Date submitted for ethics approval [1] 298374 0
10/05/2017
Approval date [1] 298374 0
27/07/2017
Ethics approval number [1] 298374 0
17/050

Summary
Brief summary
The primary objective of this study is to investigate whether Abdominal Functional Electrical Stimulation (Abdominal FES) can prevent abdominal muscle atrophy during mechanical ventilation in critically ill patients. If feasible, data will be used to design a second, larger trial on clinically relevant endpoints. The secondary objectives of this study are to analyse whether this intervention also affects: (1) the thickness of the diaphragm, (2) respiratory function, (3) ventilation duration, (4) markers for systemic inflammation, (5) Intensive Care Unit (ICU) length of stay, (6) ICU and hospital representations, (7) re-intubations, (8) mortality and (9) quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76870 0
Dr Euan McCaughey
Address 76870 0
Neuroscience Research Australia
139 Barker Street
Randwick
NSW 2031
Country 76870 0
Australia
Phone 76870 0
+61 2 9399 1827
Fax 76870 0
Email 76870 0
e.mccaughey@neura.edu.au
Contact person for public queries
Name 76871 0
Dr Euan McCaughey
Address 76871 0
Neuroscience Research Australia
139 Barker Street
Randwick
NSW 2031
Country 76871 0
Australia
Phone 76871 0
+61 2 9399 1827
Fax 76871 0
Email 76871 0
e.mccaughey@neura.edu.au
Contact person for scientific queries
Name 76872 0
Dr Euan McCaughey
Address 76872 0
Neuroscience Research Australia
139 Barker Street
Randwick
NSW 2031
Country 76872 0
Australia
Phone 76872 0
+61 2 9399 1827
Fax 76872 0
Email 76872 0
e.mccaughey@neura.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 5571 0
E.J. McCaughey, A.H. Jonkman, C.L. Boswell-Ruys, R.A. McBain, E.A. Bye, A.L. Hudson, S.C. Gandevia, D.W. Collins, L.M.A. Heunks, A.J. McLachlan, J.E. Butler (2019). Abdominal Functional Electrical Stimulation to assist ventilator weaning in critical illness: a double blinded, randomised, sham-controlled pilot study. Critical Care, 23:261
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary