ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616000948493

Ethics application status

Approved

Date submitted

12/07/2016

Date registered

18/07/2016

Date last updated

11/02/2021

Date data sharing statement initially provided

11/02/2021

Date results information initially provided

11/02/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Does in-bed cycling with critically ill patients assist to maintain muscle mass and function?

Scientific title

A randomised controlled trial of in-bed cycling with critically ill patients on maintaining quadriceps muscle mass.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

CYCLIST

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Critical illness

Intensive Care Unit Acquired Weakness (ICUAW)

Sepsis

Condition category

Condition code

Physical Medicine / Rehabilitation

Other physical medicine / rehabilitation

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention Group:
Timeframe: Within 120 hours of ICU admission until ICU discharge (28 days maximum) post ICU admission (whichever occurs sooner)

Program: In addition to usual standard of care physiotherapy interventions the intervention group will complete daily (Mon-Fri) additional progressive lower limb in-bed cycling using a bedside cycle ergometer (MOTOmed Letto 2) for 30-minutes .
Patients who are sedated or in a state of low arousal will cycle continuously and passively for 30 minutes at a cadence of 20 rpm.
Once the patient is able to follow commands they will be asked to cycle actively. The cycle ergometer will be adjusted to facilitate progression of intensity throughout the sessions (within safe limits, specified in stopping criteria). A physiotherapist with experience in prescribing exercise programs for critically ill patients will adjust the intensity of the in-bed cycling intervention based on the patients' physiological parameters and muscular endurance.
This will enable the patient to cycle in-bed either passively or actively (as able) with assistance from the cycle ergometer.
The patients’ cardiorespiratory and cardiovascular values will be monitored throughout the exercise intervention.
Patients will be progressed to exercise at the highest level of resistance that they tolerate whilst maintaining physiological values within pre-specified stopping criteria.
In-bed cycling sessions will continue until the patient completes a minimum of 5 cycle in-bed cycling sessions.
In-bed cycling sessions will continue in the acute hospital ward after discharge from ICU if the patient is discharged from ICU prior to completing 5 in-bed cycling sessions.
In-bed cycling sessions will continue until ICU discharge (28 days maximum), the maximum number of in-bed cycling sessions that could be completed is 20.

Intervention code [1]

Rehabilitation

Comparator / control treatment

Control group (standard care):
Participants in the comparator group will receive usual physiotherapy interventions whilst an inpatient in intensive care. Physiotherapy interventions will be implemented by the usual treating physiotherapists in the unit and typically include respiratory physiotherapy and exercise interventions inclusive of sitting on the edge of the bed, sit to stand transfers, sitting out of bed and walking.

Both groups will receive usual , medical, nursing and allied health care in the ICU and elsewhere in the hospital following discharge from the ICU.

Control group

Active

Outcomes

Primary outcome [1]

Percentage of change in cross-sectional area of rectus femoris measured by ultrasound scan.

Timepoint [1]

Change (from baseline) at Day 10 post study enrolment is the primary endpoint for the primary outcome
(although measurements will also be taken at other timepoints e.g. day 3, day 7, 7 days post discharge from ICU).

Secondary outcome [1]

Percentage of change in anterior to posterior muscle thickness of rectus femoris measured by ultrasound scan

Timepoint [1]

Baseline (within 24 hours of study enrolment), day 3, 7 and 10 (primary end-point) and day 7 post ICU discharge

Secondary outcome [2]

Percentage of change in anterior to posterior muscle thickness of vastus intermedius measured by ultrasound scan

Timepoint [2]

Baseline (within 24 hours of study enrolment), day 3, 7 and 10 (primary end-point) and day 7 post ICU discharge

Secondary outcome [3]

Muscle strength
Measured by Medical Research Council Sum-Score

Timepoint [3]

ICU discharge and one week post ICU discharge

Secondary outcome [4]

Muscle strength
Measured by hand-grip dynamometry

Timepoint [4]

ICU discharge and one week post ICU discharge

Secondary outcome [5]

Functional outcomes
Time to achieve functional milestones (time to stand, sit out of bed, mobilise and mobilise independently).

Timepoint [5]

Daily in ICU

Secondary outcome [6]

Functional outcome
Functional Status Score - ICU (FSS-ICU)

Timepoint [6]

ICU discharge and one week post ICU discharge

Secondary outcome [7]

Functional outcome
ICU Mobility Scale (IMS).

Timepoint [7]

Measured daily in ICU

Secondary outcome [8]

Walking endurance measured by the 6 minute walk test

Timepoint [8]

One week post ICU discharge

Secondary outcome [9]

Quality of Life measured by the EQ-5D

Timepoint [9]

Day 10 post ICU admission and 3 months post discharge

Secondary outcome [10]

Incidence of delirium measured by the Confusion Assessment Method for the intensive care unit (CAM-ICU)

Timepoint [10]

Daily whilst an inpatient in ICU

Secondary outcome [11]

Duration of delirium measured by the Confusion Assessment Method for the intensive care unit (CAM-ICU)

Timepoint [11]

Daily whilst an inpatient in ICU

Secondary outcome [12]

Patient perspectives (intervention group) assessed by a customised acceptability of intervention questionnaire

Timepoint [12]

Day 10 post ICU admission or at completion of cycle ergometry sessions.

Eligibility

Key inclusion criteria

Critically ill patients admitted to ICU who are:
(i) expected to require >48 hours of mechanical ventilation,
(ii) able to provide consent or have a family member consent on their behalf,
(iii) enrolled into the study within 96 hours of ICU admission,
(iv) expected to remain in ICU for >48 hours following study enrolment.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

i) The presence of a pre-existing condition that is likely to impair mobility or the assessment of mobility following enrolment (e.g. neurological, musculoskeletal, cognitive or mental health disorder likely to impair daily function)
ii) Diagnosed or suspected acute primary brain lesion (e.g. traumatic brain injury, intracranial haemorrhage, stroke, hypoxic brain injury or neuromuscular disorder) that is likely to impair daily function.
iii) Injuries where in-bed cycling would be contraindicated (e.g. some spinal / pelvic / lower limb orthopaedic injuries / open abdominal wound).
iv) Death is deemed to be imminent or inevitable during this admission
v) Obesity (greater than 135 kg) as the maximum weight capacity for the in-bed cycle ergometer is 135 kg. (MOTOmed Letto 2)
vi) Has acute deep vein thrombosis or pulmonary embolism
vii) Acute coronary syndrome (evidence of coronary ischaemia e.g. chest pain or ECG changes)
viii) Uncontrolled seizures or status epilepticus
ix) Pregnancy

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)

The random allocation sequence, with variable block sizes will be concealed and uploaded on the Research Electronic Data Capture (REDCap) secure web based clinical trial workflow software. The REDCap randomisation module will be utilised to only reveal the allocation of the participant to either the control or intervention group to the intervention co-coordinator for the trial.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Offsite research personnel not involved in the day to day operation of the trial will use computerised random number generation to create a randomisation sequence. A treatment to control ratio of 1:1 and (random) block sizes will be used to minimise risk of potential differences in group sizes. Only the randomisation sequence generator will know the block sizes used.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Descriptive statistics and generalized linear mixed models will be used to examine the effect of group allocation (intervention vs. control) on the primary and secondary outcomes. As this is a randomised trial we do not plan to adjust for potential confounders (e.g., age, gender, comorbidities), but will compare the characteristics of the sample by treatment group and may adjust if a potential confounder differs greatly between groups).
Given the repeated measures design, a sample size calculation has estimated this sample will have 80% power to detect a 2.9% between group mean difference in cross sectional area change of Rectus Femoris; assuming alpha 0.05, standard deviation of 6%, and correlation of 0.5% between assessments after taking into account a drop-out rate of up to 20% . Data will be analysed and reported using an intention to treat analysis,
Additional analysis: A per protocol analysis may also be conducted (as a secondary or sensitivity analysis) if substantial variations from the intended treatment protocol are observed. If conducted, per protocol analysis will comprise participants who adhere to the protocol and received at least 80% of training sessions (minimum of 4 sessions).

The following sub-analyses are planned:
Analysis of muscle wasting examining the association with: number/ severity of vital organs assessed to have dysfunction/failure utilising a Sequential Organ Failure Score (SOFA); severity of illness on admission to ICU utilising APACHE II and APACHE III data; rectus femoris muscle cross sectional area at initial assessment.; number of days to a patient commences active activity; sedative and paralytic medications.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

18/07/2016

Actual

26/07/2016

Date of last participant enrolment

Anticipated

Actual

7/05/2018

Date of last data collection

Anticipated

Actual

7/11/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Princess Alexandra Hospital - Woolloongabba

Recruitment postcode(s) [1]

4102 - Woolloongabba

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Metro South Health Centres for Health Research

Address [1]

Princess Alexandra Hospital
Centres for Health Research
Level 7 Translational Research Institute
37 Kent Street
Woolloongabba
QLD 4102

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

Princess Alexandra Hospital

Address [2]

Ipswich Rd
Woolloongabba
QLD 4102

Country [2]

Australia

Primary sponsor type

Individual

Name

Marc Nickels

Address

Physiotherapy Department
Princess Alexandra Hospital
Ipswich Rd
Woolloongabba
QLD 4102

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Assoc Prof Steven McPhail

Address [1]

Centre for Functioning and Health Research
Level 3 Buranda Village
Cnr. Ipswich Rd and Cornwell St
Buranda
QLD 4102

Country [1]

Australia

Secondary sponsor category [2]

Individual

Name [2]

Professor Leanne Aitken

Address [2]

School of Health Sciences,
City University London
Northampton Square
London EC1V 0HB

Country [2]

United Kingdom

Secondary sponsor category [3]

Individual

Name [3]

Assoc Prof Adrian Barnett

Address [3]

Queensland University of Technology,
60 Musk Avenue,
Kelvin Grove,
QLD 4059

Country [3]

Australia

Secondary sponsor category [4]

Individual

Name [4]

Dr James Walsham

Address [4]

Intensive Care Unit
Princess Alexandra Hospital
Ipswich Rd
Woolloogabba,
QLD 4102

Country [4]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Metro South Human Research Ethics Committee

Ethics committee address [1]

Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba
QLD 4102

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

28/04/2016

Ethics approval number [1]

HREC/16/QPAH/193

Summary

Brief summary

Critically ill patients often require prolonged mechanical ventilation for periods greater than 48 hours. It has been identified that skeletal muscle wasting occurs early and rapidly during the first week of critical illness. Despite international recommendations to commence activity as early as possible with critically ill patients it has been identified that exercise interventions are rarely initiated when a patient is on mechanical ventilation. This leads to prolonged immobility and may contribute to the development of ICU Acquired Weakness (ICUAW).

A randomised controlled trial (RCT) will compare outcomes of critically ill patients who receive standard physiotherapy (control group) and those who complete additional in-bed cycling intervention sessions. This will enable comparison of outcomes to assist clinicians to determine if additional in-bed cycling sessions may be beneficial with critically ill patients.

Objectives:
To determine:
(1) if in-bed cycling in addition to standard care is effective in reducing the rate of rectus femoris (RF) cross-sectional area (CSA) atrophy and intensive care unit acquired weakness (ICUAW) in patients requiring > 48 hrs of mechanical ventilation compared to standard care;
(2) whether in-bed cycling in addition to standard care improved functional and cognitive outcomes in patients requiring > 48 hours of mechanical ventilation compared to standard care.

Trial Design: Two (parallel) arm, preliminary randomised control trial with assessor blinding.

In summary, this study aims to examine if addition of an in-bed cycling intervention with critically ill patients reduces the loss of thigh muscle mass. Also to examine if in-bed cycling improves functional and cognitive outcomes post intensive care discharge.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Mr Marc Nickels

Address

Physiotherapy Department
Princess Alexandra Hospital
Ipswich Rd
Woollgabba
QLD 4102

Country

Australia

Phone

+61 7 31762401

Fax

[email protected]

Contact person for public queries

Name

Mr Marc Nickels

Address

Physiotherapy Department
Princess Alexandra Hospital
Ipswich Rd
Woollgabba
QLD 4102

Country

Australia

Phone

+61 7 31762401

Fax

[email protected]

Contact person for scientific queries

Name

Mr Marc Nickels

Address

Physiotherapy Department
Princess Alexandra Hospital
Ipswich Rd
Woollgabba
QLD 4102

Country

Australia

Phone

+61 7 31762401

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
10593	Study protocol		https://bmjopen.bmj.com/content/7/10/e017393
10594	Statistical analysis plan		https://bmjopen.bmj.com/content/7/10/e017393

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Effect of in-bed cycling on acute muscle wasting i... [More Details]
Study results article	Yes		Acceptability, safety, and feasibility of in-bed c... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Effect of in-bed cycling on acute muscle wasting in critically ill adults: A randomised clinical trial.	2020	https://dx.doi.org/10.1016/j.jcrc.2020.05.008
Embase	Predictors of acute muscle loss in the intensive care unit: A secondary analysis of an in-bed cycling trial for critically ill patients.	2023	https://dx.doi.org/10.1016/j.aucc.2022.12.015
Embase	Critical Care Cycling Study (CYCLIST) trial protocol: A randomised controlled trial of usual care plus additional in-bed cycling sessions versus usual care in the critically ill.	2017	https://dx.doi.org/10.1136/bmjopen-2017-017393

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically