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Trial registered on ANZCTR


Registration number
ACTRN12616000177459
Ethics application status
Approved
Date submitted
4/02/2016
Date registered
11/02/2016
Date last updated
6/12/2018
Date data sharing statement initially provided
6/12/2018
Date results information initially provided
6/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does electrically stimulating the leg muscles of people on life saving artificial heart lung machines protect them from damage to their feet?
Scientific title
Effects of percutaneous Neuromuscular Electrical Stimulation (NMES) application to the Quadriceps muscle on vascular viability of the foot in critically ill patients undergoing Extra Corporeal Membrane Oxygenation (ECMO) via femoral cannulation
Secondary ID [1] 288477 0
Nil known
Universal Trial Number (UTN)
U1111-1179-2064
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pedal blood flow in patients undergoing Extra Corporeal Membrane Oxygenation (ECMO) 297528 0
Condition category
Condition code
Physical Medicine / Rehabilitation 297716 297716 0 0
Physiotherapy
Cardiovascular 297782 297782 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is a randomised, sham controlled, single blind, crossover trial.
Participants will be any patient aged greater than 18 years undergoing femoral cannulation Extra Corporeal Membrane Oxygenation (ECMO) who would normally receive muscle stimulation as part of their standard physiotherapy care in the Intensive Care Unit (ICU) of the study site.
The intervention will be a single 30 minute muscle stimulation session (versus a single 30 minute sham intervention where the muscle stimulator will be attached to the patient but inactive) applied by a physiotherapist to the thigh muscles of the participants . Electrodes will be applied to the treatment limb using a standardised placement. The muscle stimulator unit (NeuroTrac Sports dual channel NMES unit - Verity Medical) with a user customisable output will produce a dual channel synchronised delivery of an asymmetrical rectangular biphasic waveform with zero DC current, applied with a ramp up time of 2 seconds and frequency (pulse rate) of 35-50 Hz. Pulse duration will be 450 microseconds, with a current delivery “on” time of 5 seconds and an “off” time of 10 seconds. Initial current intensity will be zero mA which will be titrated to a intensity sufficient to obtain a visible contraction of the thigh muscles and a palpable tensioning of the patellar ligament, if no contraction is obtained the amplitude will be adjusted to the maximum deliverable amplitude (up to 90 mA depending on skin resistance). The investigators will be present during the intervention and sham applications to ensure adherence.
Tissue perfusion at the foot during both the intervention and sham treatments will then be measured noninvasively via a combination of imaging (Moor Instruments FLPI 2 laser speckle contrast blood flow imager)and non imaging (Perimed - Periflux System 5000 with PF 5010 Laser Doppler Perfusion Monitor unit) laser Doppler flowmetry, and trancutaneous oximetry.as measured by a Radiometer TCM4 monitor
A 1/2 hour washout period will then occur before the crossover intervention.
Intervention code [1] 293816 0
Treatment: Other
Comparator / control treatment
Crossover study where participants will receive both the active treatment and a sham treatment
Control group
Placebo

Outcomes
Primary outcome [1] 297248 0
Primary outcome 1: Changes in local microvascular blood flow at the foot as measured by non imaging laser Doppler flowmetry (Perimed - Periflux System 5000 with PF 5010 Laser Doppler Perfusion Monitor unit) and imaging laser Doppler flowmetry (Moor Instruments FLPI 2 laser speckle contrast blood flow imager) during the application of muscle stimulation (or sham treatment) via a NeuroTrac Sports dual channel NMES unit (Verity Medical)
Timepoint [1] 297248 0
Measurements will be recorded at the 15 and 30 minute time points post application of the muscle stimulator (or sham treatment) and 5 minutes post cessation of treatment (or sham)
Primary outcome [2] 297250 0
Primary outcome 2: Changes in trancutaneous oximetery (tcpO2) at the foot, as measured by a Radiometer TCM4 monitor during application of muscle stimulation (or sham treatment) via a NeuroTrac Sports dual channel NMES unit (Verity Medical)
Timepoint [2] 297250 0
Measurements will be recorded at the 15 and 30 minute time points post application of the muscle stimulator (or sham treatment) and 5 minutes post cessation of treatment (or sham)
Secondary outcome [1] 320500 0
No secondary outcome measures are anticipated as a result of this study
Timepoint [1] 320500 0
not applicable

Eligibility
Key inclusion criteria
The study participants will be any patient undergoing ECMO via femoral cannulation in the ICU of The Prince Charles Hospital who would normally receive muscle stimulation as part of their standard physiotherapy care and who do not meet any of the exclusion criteria.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients for whom consent was unable to be obtained
Male or female < 18 years old
Inability to independently transfer from bed to chair at baseline before hospital
admission
Known primary systemic neuromuscular disease at ICU admission
Known intracranial process associated with localised weakness e.g. cerebrovascular
accident (CVA) at ICU admission
End-stage malignancy
Diseases with systemic vascular involvement
Bone fractures or skin lesions / open wounds on the area to be treated
Epilepsy
Heavy ischemia of the area to be treated
Patients with permanent pacemaker (PPM) / implantable cardioverter-defibrillator (ICD)
Brain death
Allergic reaction to the electrodes
Significant lower limbs oedema
Obesity (Body Mass Index > 35kg/m2)
Cardiovascular instability as determined clinically by the treating therapist or medical
staff
If the patient is receiving neuromuscular blockers
If the patient displayed clinical signs of treatment intolerance. For sedated and
intubated patients; the level of tolerance will be estimated by assessing signs of distress
(e.g. significant heart rate (HR) and blood pressure (BP) alterations and/or presence of
grimacing) as well as regular skin checks

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The key statistics are the within-patient differences in blood flow between the
intervention and the control/sham and determining if there are differences over the
electrical stimulation’s application (baseline, 15 and 30 minutes). Using within-patient
differences means that patient characteristics (such as age) are not important as they
are controlled for by design. Therefore, the non-parametric tests of Mann-Whitney,
Kruskal-Wallis and other appropriate if required tests (e.g. if there are carry-over effects
from the study) will be used to determine the effects of the intervention. As the effects of
this intervention are unknown, it is difficult to calculate an appropriate sample size.
Therefore, this proposal is using a convenience sample of 20 patients that are likely to
be recruited during the study period.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
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)
QLD
Recruitment hospital [1] 5230 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 12701 0
4032 - Chermside South

Funding & Sponsors
Funding source category [1] 292821 0
Charities/Societies/Foundations
Name [1] 292821 0
The Prince Charles Hospital Foundation
Address [1] 292821 0
GPO Box 3175
Brisbane QLD 4001
Country [1] 292821 0
Australia
Primary sponsor type
Individual
Name
Paul McCormack
Address
Physiotherapy Department
The Prince Charles Hospital
Rode Road
Chermside, QLD , 4032
Country
Australia
Secondary sponsor category [1] 291564 0
None
Name [1] 291564 0
Address [1] 291564 0
Country [1] 291564 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294327 0
Metro North Hospital and Health Service - The Prince Charles Hospital Human Research Ethics Committee (HREC)
Ethics committee address [1] 294327 0
Human Research Ethics Committee
Metro North Hospital and Health Service
The Prince Charles Hospital
Building 14
Rode Road, Chermside QLD 4032
Ethics committee country [1] 294327 0
Australia
Date submitted for ethics approval [1] 294327 0
26/10/2015
Approval date [1] 294327 0
04/11/2015
Ethics approval number [1] 294327 0
HREC/15/QPCH/192

Summary
Brief summary
This study will provide valuable data on the safe and efficacious use of muscle stimulation therapies currently applied by physiotherapists to patients receiving lifesaving Extra Corporeal Membrane Oxygenation (ECMO) which provides external cardiac and respiratory support for patients. Patients receiving ECMO are critically unwell and their prolonged ICU stays are associated with major loss of muscle mass and strength, and also with impaired physical function.

Previously published experience from The Prince Charles Hospital (TPCH) suggests that this same patient group maybe at increased risk of foot necrosis (tissue death) either as a result of their disease process or machine techniques from the ECMO.

Muscle stimulation is currently utilised by physiotherapists in TPCH ICU in an attempt to preserve the muscle mass of critically ill immobilised patients. Its effects in patients receiving ECMO have not been investigated.

Changes in regional blood flow are also associated with the application of muscle stimulation.This study will demonstrate if a beneficial improvement in foot blood flow occurs as a result of muscle stimulation application which may prevent the development of foot problems in patients undergoing rescue therapy via ECMO. It will also be used to guide future research studies, and potentially therapy at this and other centres.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63302 0
Mr Paul McCormack
Address 63302 0
Physiotherapy Department
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 63302 0
Australia
Phone 63302 0
+61 7 31395310
Fax 63302 0
Email 63302 0
paul.mccormack@health.qld.gov.au
Contact person for public queries
Name 63303 0
Mr Paul McCormack
Address 63303 0
Physiotherapy Department
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 63303 0
Australia
Phone 63303 0
+61 7 31395310
Fax 63303 0
Email 63303 0
paul.mccormack@health.qld.gov.au
Contact person for scientific queries
Name 63304 0
Mr Paul McCormack
Address 63304 0
Physiotherapy Department
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 63304 0
Australia
Phone 63304 0
+61 7 31395310
Fax 63304 0
Email 63304 0
paul.mccormack@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary