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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] 252737 0
NIL
Universal Trial Number (UTN)
Trial acronym
i-PERFORM Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 258237 0
Intensive Care Unit Acquired Weakness 258274 0
Condition category
Condition code
Physical Medicine / Rehabilitation 258416 258416 0 0
Physiotherapy
Musculoskeletal 258465 258465 0 0
Other muscular and skeletal disorders
Infection 258466 258466 0 0
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] 257254 0
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] 259264 0
Acute Care Index of Function
(ACIF)

ACIF will assess physical functional performance
Timepoint [1] 259264 0
Baseline and at ICU Discharge
Primary outcome [2] 259265 0
Short Form 36 Medical Study
(SF-36)

SF-36 will assess quality of life
Timepoint [2] 259265 0
Baseline and at ICU Discharge
Primary outcome [3] 259266 0
Hospital Anxiety Depression Scale
(HADS)

HADS will assess psychological components
Timepoint [3] 259266 0
Baseline and at ICU Discharge
Secondary outcome [1] 265664 0
Physical Function ICU Test
(PFIT)

PFIT will assess physical functional exercise capacity
Timepoint [1] 265664 0
Baseline and at ICU discharge and 6 month follow up
Secondary outcome [2] 265665 0
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] 265665 0
Week 1 :
Pre, 30minutes post each intervention session

Week 2 till discharge :
Pre, 30minutes post each intervention session twice weekly
Secondary outcome [3] 265666 0
Blood Mitochondrial Deoxyribonucleic Acid
(mtDNA)

Peripheral mtDNA levels will assess oxidative stress
Timepoint [3] 265666 0
Baseline and then weekly until discharge from ICU
Secondary outcome [4] 265667 0
Blood Lactate

Blood lactate levels will assess level of lactate as an indicator of oxidative stress
Timepoint [4] 265667 0
Pre, 5 minutes and 30minutes post each intervention session
Secondary outcome [5] 265668 0
Near Infrared Spectroscopy
(NIRS)

NIRS will assess muscle oxygenation
Timepoint [5] 265668 0
Pre and post each intervention session
Secondary outcome [6] 265669 0
Orthogonal Polarisation Spectral Imaging (OPS)

OPS will assess microcirculation
Timepoint [6] 265669 0
Pre and post intervention each intervention session
Secondary outcome [7] 265730 0
Bioelectrical Imepdance Analysis (BIA)

BIA will assess quantity of muscle mass loss or gain
Timepoint [7] 265730 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
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] 6858 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 14523 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 257699 0
Charities/Societies/Foundations
Name [1] 257699 0
Physiotherapy Research Foundation
Address [1] 257699 0
Physiotherapy Research Foundation
Level 1, 1175 Toorak Road,
Camberwell VIC 3124
Country [1] 257699 0
Australia
Funding source category [2] 257700 0
Charities/Societies/Foundations
Name [2] 257700 0
The Intensive Care Foundation
Address [2] 257700 0
The Intensive Care Foundation Office
Level 2, 10 Ievers Terrace
Carlton, Victoria 3053
Country [2] 257700 0
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] 256914 0
None
Name [1] 256914 0
Address [1] 256914 0
Country [1] 256914 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259731 0
The Human Research Ethics Committee of Royal Brisbane and Women's Hospital
Ethics committee address [1] 259731 0
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] 259731 0
Australia
Date submitted for ethics approval [1] 259731 0
19/07/2010
Approval date [1] 259731 0
31/08/2010
Ethics approval number [1] 259731 0
HREC/10/QRBW/279
Ethics committee name [2] 259732 0
Medical Research Ethics Committee of The University of Queensland
Ethics committee address [2] 259732 0
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] 259732 0
Australia
Date submitted for ethics approval [2] 259732 0
01/09/2010
Approval date [2] 259732 0
16/09/2010
Ethics approval number [2] 259732 0
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 31677 0
Address 31677 0
Country 31677 0
Phone 31677 0
Fax 31677 0
Email 31677 0
Contact person for public queries
Name 14924 0
Ms Geetha Kayambu
Address 14924 0
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 14924 0
Australia
Phone 14924 0
+61 7 33465193
Fax 14924 0
+61 7 33655192
Email 14924 0
g.kayambu@uq.edu.au
Contact person for scientific queries
Name 5852 0
Ms Geetha Kayambu
Address 5852 0
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 5852 0
Australia
Phone 5852 0
+61 7 33465193
Fax 5852 0
+61 7 33655192
Email 5852 0
g.kayambu@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary