ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12610000808044

Ethics application status

Approved

Date submitted

22/09/2010

Date registered

27/09/2010

Date last updated

24/10/2016

Type of registration

Prospectively registered

Titles & IDs

Public title

Improving Outcomes in Critical Illness with Early Rehabilitation

Scientific title

Mobilising Critically Ill patients:
Physiological and Functional Outcomes following Early Rehabilitation in Sepsis

Secondary ID [1]

NIL

Universal Trial Number (UTN)

Trial acronym

i-PERFORM Trial

Linked study record

Health condition

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

Sepsis

Intensive Care Unit Acquired Weakness

Condition category

Condition code

Physical Medicine / Rehabilitation

Physiotherapy

Musculoskeletal

Other muscular and skeletal disorders

Infection

Other infectious diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention Arm:
Adminster Rehabiliation package ( targeted exercises)
by physiotherapist in the intensive care unit (ICU).

The intervention group will receive an early, specific, targeted rehabilitation program involving electrical muscle stimulation, passive and active range of motion exercises, mobilisation out of bed, tilt-table therapy, arm and leg ergometry exercises and ambulation.

Commencement: 48hrs following Mechanical Ventilation
Duration and Frequency: 30 mins x 1-2 day
Overall duration: From recruitment till ICU discharge
Mode of adminstration: Individual exercise prescription by a physiotherapist

Intervention code [1]

Rehabilitation

Comparator / control treatment

Control Arm:
Usual care

The control group will receive usual care from the ICU staff i.e. sitting out of bed and walking.

Commencement: Anytime during ICU stay after recruitment.
Duration and Frequency: As prescribed by ICU staff.
Overall duration: From recruitment till ICU discharge.
Mode of adminstration: As per usual care by ICU staff.

Control group

Active

Outcomes

Primary outcome [1]

Acute Care Index of Function
(ACIF)

ACIF will assess physical functional performance

Timepoint [1]

Baseline and at ICU Discharge

Primary outcome [2]

Short Form 36 Medical Study
(SF-36)

SF-36 will assess quality of life

Timepoint [2]

Baseline and at ICU Discharge

Primary outcome [3]

Hospital Anxiety Depression Scale
(HADS)

HADS will assess psychological components

Timepoint [3]

Baseline and at ICU Discharge

Secondary outcome [1]

Physical Function ICU Test
(PFIT)

PFIT will assess physical functional exercise capacity

Timepoint [1]

Baseline and at ICU discharge and 6 month follow up

Secondary outcome [2]

Blood Assays for Inflammatory Biomarkers :
Interleukin 6 (IL 6), Interleukin 10(IL 10), Tumor Necrosis Factor aplha) (TNF alpha)

Blood assays will assess levels of anti-inflammatory and pro-inflammatory cytokines

Timepoint [2]

Week 1 :
Pre, 30minutes post each intervention session

Week 2 till discharge :
Pre, 30minutes post each intervention session twice weekly

Secondary outcome [3]

Blood Mitochondrial Deoxyribonucleic Acid
(mtDNA)

Peripheral mtDNA levels will assess oxidative stress

Timepoint [3]

Baseline and then weekly until discharge from ICU

Secondary outcome [4]

Blood Lactate

Blood lactate levels will assess level of lactate as an indicator of oxidative stress

Timepoint [4]

Pre, 5 minutes and 30minutes post each intervention session

Secondary outcome [5]

Near Infrared Spectroscopy
(NIRS)

NIRS will assess muscle oxygenation

Timepoint [5]

Pre and post each intervention session

Secondary outcome [6]

Orthogonal Polarisation Spectral Imaging (OPS)

OPS will assess microcirculation

Timepoint [6]

Pre and post intervention each intervention session

Secondary outcome [7]

Bioelectrical Imepdance Analysis (BIA)

BIA will assess quantity of muscle mass loss or gain

Timepoint [7]

Baseline and then weekly until discharge from ICU

Eligibility

Key inclusion criteria

Acutely ill patients who are mechanically ventilated for longer than 48 hours with documented sepsis or those with strong clinical suspicion of possible sepsis

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Patients with head injuries, burns, spinal injuries, multiple fractured lower limbs and acute coronary syndrome

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)

Computerised sequence generated randomisation. Participants will be randomisied either into the intervention arm or control arm of the study.
The randomization sequence will be concealed from consent designee research staff and protected by an electronic password.

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

Patients will be consented by one of three of the chief investigators and randomized to one of two groups (computer generated randomization) at 48 hours of mechanical ventilation.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/09/2010

Actual

31/10/2010

Date of last participant enrolment

Anticipated

Actual

31/12/2012

Date of last data collection

Anticipated

Actual

30/06/2013

Sample size

Target

252

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Royal Brisbane & Womens Hospital - Herston

Recruitment postcode(s) [1]

4029 - Herston

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Physiotherapy Research Foundation

Address [1]

Physiotherapy Research Foundation
Level 1, 1175 Toorak Road,
Camberwell VIC 3124

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

The Intensive Care Foundation

Address [2]

The Intensive Care Foundation Office
Level 2, 10 Ievers Terrace
Carlton, Victoria 3053

Country [2]

Australia

Primary sponsor type

Individual

Name

Ms Geetha Kayambu

Address

Burns Trauma and Critical Care Research Centre (BTCCRC)
School of Medicine, The University of Queensland
Level 7, Block 6
Royal Brisbane and Women's Hospital
Bowen Bridge Rd
Herston QLD 4029

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Human Research Ethics Committee of Royal Brisbane and Women's Hospital

Ethics committee address [1]

Office of the Human Research Ethics Committee
Level 7, Block 7
Royal Brisbane and Women's Hospital
Bowen Bridge Rd
Herston QLD 4029

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/07/2010

Approval date [1]

31/08/2010

Ethics approval number [1]

HREC/10/QRBW/279

Ethics committee name [2]

Medical Research Ethics Committee of The University of Queensland

Ethics committee address [2]

Medical Research Ethics Committee 
Research and Innovation Division
The University of Queensland
Cumbrae-Stewart
Building No.72
Research Road
St.Lucia QLD 4072

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

01/09/2010

Approval date [2]

16/09/2010

Ethics approval number [2]

2010001178

Summary

Brief summary

Admission to an intensive  care unit occurs due to the either major trauma or critical illness. Approximately 12% of admissions to intensive care unit (ICU) are for sepsis and a further 20% will develop sepsis, which has major immediate and long term effects on morbidity and mortality.

If the patient survives the initial illness, a combination of the detrimental effects of the major illness stress response, nutrition, glucose levels, inflammatory mediators, immobility, hospital acquired infections and certain pharmacological agents can result in the loss of large amounts of muscle mass attributed to a proteolytic or protein degradation process or specific critical care weakness syndromes. This all results in further inability to sit, walk, swallow and breathe and a decrease in endurance in respiratory muscles, necessitating a longer time on the ventilator, increased stay in ICU, increased potential for nosocomial infection and subsequent increased morbidity and mortality. These patients are frequently depressed and anxious which has been shown to be associated with an inability to wean from the ventilator and be readmitted to intensive care when eventually discharged. Readmission will result in a further increase in morbidity and mortality. Combined, these factors escalate health care resource use during and beyond the initial hospital stay.

Studies investigating the quality of life of critically ill patients on discharge from hospital have found severe psychological and physical problems. Overall ICU survivors have been found to have a lower health related quality of life. ICU patients specifically with sepsis can have a worse outcome.  

Preliminary evidence suggests that simple physical interventions may prevent detrimental effects of intensive care stay. Muscle stretch and passive movement can decrease levels of inflammatory markers. These indicate there is potential to prevent protein degradation and loss of muscle mass. 

Oxidative stress which refers to stress of any kind, in the event of limited oxygen supply, is known to induce inflammatory responses and destroy cells in critically ill patients that can lead to an increased mortality rate. In trying to prevent oxidative stress, many critically ill patients are not mobilised in the early stages of ICU admission which contributes to loss of muscle mass and decline in functional ability upon ICU discharge. During rehabilitation in the ICU, it is hard to predict the level of exhaustion or fatigue the intensity of the exercise induces on the patients. There has been some evidence to support that both locomotive and breathing muscles in sepsis show dramatic decreases in mitochondrial content, causing an acute lack of energy when the muscle is activated again following discharge. This highlights the importance of maintaining the use of respiratory and skeletal muscles during the disease process. In surviving septic patients, energy expansion is limited and exhaustive exercise can worsen this condition. 

Patients with sepsis demonstrate high levels of lactate in the blood which can cause fatigue. Understanding the effects of acute exercise on lactate levels in septic patients can help predict a safe rehabilitation scope. Early use of skeletal muscles can contribute to lactate clearance. Regular low intensity exercise training can also increase the rate of lactate clearance . This suggests there is potential that low intensity exercise can control lactate levels and even help reduce it. This study will investigate the associations between early rehabilitation and fatigue.

When a patient initially develops sepsis it is recommended that they do not receive physiotherapy intervention (even passive movements) as it is believed that during an inflammatory process they are too unstable. Some ICU's do not include rehabilitation either in the belief it is unsafe or due to insufficient staffing levels. 

This study will determine whether early rehabilitation for septic patients with sepsis in ICU is clinically effective and appropriate. It will provide insight and evidence on physiological outcomes that will determine the safety of early mobilisation in critically ill patients. With evidence for early targeted rehabilitation in the ICU, there can be facilitated early functional recovery in the critically ill patients and decreased stay in the ICU.

Trial website

Trial related presentations / publications

1. Kayambu, Geetha, Boots, Robert J. and Paratz, Jennifer D. (2011) A prospective randomised controlled trial investigating functional and physiological outcomes following early rehabilitation in sepsis: The i-PERFORM Trial (Protocol Article). BMC Anesthesiology, 11 21-1-21-11. doi:10.1186/1471-2253-11-21

2. Kayambu, Geetha, Boots, Robert and Paratz, Jennifer (2013) Physical therapy for the critically ill in the ICU: A systematic review and meta-analysis. Critical Care Medicine, 41 6: 1543-1554. doi:10.1097/CCM.0b013e31827ca637 

3. Kayambu, Geetha, Boots, Robert and Paratz, Jennifer (2015) Early physical rehabilitation in intensive care patients with sepsis syndromes: a pilot randomised controlled trial. Intensive Care Medicine, 41 5: 865-874. doi:10.1007/s00134-015-3763-8

4. Paratz, Jennifer D. and Kayambu, Geetha (2011) Early exercise and attenuation of myopathy in the patient with sepsis in ICU. Physical Therapy Reviews, 61 1: 58-65. doi:10.1179/1743288X11Y.0000000002

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Ms Geetha Kayambu

Address

Burns Trauma and Critical Care Research Centre (BTCCRC)
The University of Queensland
School of Medicine
Level 7, Block 6,
Royal Brisbane and Women's Hospital
Herston QLD 4029

Country

Australia

Phone

+61 7 33465193

Fax

+61 7 33655192

g.kayambu@uq.edu.au

Contact person for scientific queries

Name

Ms Geetha Kayambu

Address

Burns Trauma and Critical Care Research Centre (BTCCRC)
The University of Queensland
School of Medicine
Level 7, Block 6,
Royal Brisbane and Women's Hospital
Herston QLD 4029

Country

Australia

Phone

+61 7 33465193

Fax

+61 7 33655192

g.kayambu@uq.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Early rehabilitation in sepsis: A prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article).	2011	https://dx.doi.org/10.1186/1471-2253-11-21

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

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