Clinical trial NCT03133377: Treatment of Invasively Ventilated Adults With Early Activity and Mobilisation
Official title: A Prospective Multicentre Phase III Randomised Controlled Trial of Early Activity and Mobilisation Compared With Standard Care in Invasively Ventilated Patients in Intensive Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Critically Ill, Mechanically Ventilated
Keywords: Early activity and mobilization, rehabilitation, intensive care
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: ANZICS Clinical Trials Group
name: Medical Research Institute of New Zealand
name: Intensive Care National Audit & Research Centre
First posted: 2017-04-28
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to evaluate the effect of early activity and mobilisation during prolonged IMV on the composite outcome "days alive and out of hospital to day 180". The effect of the intervention on mortality, physical, cognitive and psychological function at 180 days, as well as cost-effectiveness of the intervention, will also be evaluated. The study will also explore process of care measures and baseline physiology and ICU mobility outcomes.

The hypothesis is that, in ICU patients expected to require prolonged IMV, early activity and mobilisation increases the number of days alive and at home to day 180 when compared with standard care.

Detailed description: The TEAM Trial is a definitive phase III multi-centre randomised controlled trial in mechanically ventilated patients. Supported by compelling preliminary data, the trial will determine whether early activity and mobilisation during mechanical ventilation improves days alive and at home at 6 months compared to standard care. Recruiting 750 patients, this will be the largest trial ever conducted of early mobilisation.

Patients allocated to the early activity and mobilisation protocol (intervention group) will be assessed by a physiotherapist daily during the ICU stay to determine the highest level of mobility. This will determine the dosage and type of exercise that will be delivered, led by the physiotherapist with assistance from the multidisciplinary team. For both groups, concomitant care will be guided by the treating clinician. In addition, all post-ICU patient management will be at the discretion of the patient's ward-based treating physicians.

Patients will be randomized via web-based system and de-identified data will be collected on the following: baseline demographics; comorbidities; sedatives, analgesics, corticosteroids and neuromuscular blockers; pain/sedation/delirium scores; tracheostomy, intubation and renal replacement therapy. The intervention will be administered during the ICU stay upto 28days and the Day 180 follow up will be conducted centrally.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 years or older.
2. Intubated and expected to remain invasively mechanically ventilated the day after tomorrow.
3. Sufficient cardiovascular stability to make mobilisation potentially possible, as indicated by:

   1. the absence of current brady-arrhythmia requiring pharmacological support
   2. a current ventricular rate ≤ 150 bpm
   3. most recent lactate ≤ 4.0 mmol/L
   4. current combined noradrenaline/adrenaline infusion rate of ≤ 0.2 mcg/kg/min, OR if noradrenaline/adrenaline infusion rate has increased by more than 25% in the last 6 hours, dose must be \<0.1 mcg/kg/min.
   5. most recent cardiac index ≥ 2.0 L/min/m2 (where measured)
   6. no current requirement for VA ECMO
4. Sufficient respiratory stability to make mobilisation potentially possible, as indicated by:

   1. current FiO2 ≤ 0.6
   2. current PEEP ≤ 16 cm H20
   3. an absence of current requirement for NO, prone ventilation, neuromuscular blockers, ventilation, prostacyclin, VV ECMO or HFOV
   4. current RR ≤ 45 bpm

Exclusion Criteria:

1. Dependent for activities of daily living in the month prior to current ICU admission (gait aids are acceptable).
2. Documented cognitive impairment.
3. Proven or suspected acute primary brain pathology (e.g. traumatic brain injury, stroke, hypoxic brain injury).
4. Proven or suspected spinal cord injury or other neuromuscular disease that will result in permanent or prolonged weakness (not including ICU acquired weakness).
5. Has rest in bed orders and/or has bilateral non-weight bearing orders for the lower limbs.
6. Life expectancy less than 180 days due to a chronic or underlying medical condition.
7. Death is deemed inevitable as a result of the current illness and either the patient or treating clinical or substitute decision maker are not committed to full active treatment.
8. Unable to communicate in the official local language.
9. This is not the first ICU admission in the index hospital admission.
10. Fulfilled all inclusion criteria and none of the exclusion criteria ≥ 72 hours

Primary outcomes:
measure: Number of days alive and out of hospital
timeFrame: between randomisation and 180 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: From date of randomisation up to180days.
measure: Time from randomisation until death
timeFrame: From date of randomisation unitl date of death from all cause, censored at 180days
measure: Ventilator-free days
timeFrame: From date of randomisation until day 28
measure: ICU-free days
timeFrame: From date of randomisation until day 28
measure: Quality of life and health status measured using the European Quality of Life 5 Dimensions 5 Level (EQ5D-5L)
timeFrame: Assessed at 180days
measure: Independent activities of daily living measured with Barthel Activities of Daily Living (ADL) Index and The Lawton Instrumental Activities of Daily Living Scale (IADL)
timeFrame: Assessed at 180days
measure: Generic function and disability measured with the World Health Organisation's Disability Assessment Schedule (WHODAS)
timeFrame: Assessed at 180days
Other outcomes:
measure: Delirium free days
timeFrame: From date of randomisation until day 28
measure: Cognitive function measured using Montreal Cognitive Assessment (MOCA-Blind)
timeFrame: Assessed at 180days
measure: Psychological function measured using Hospital Anxiety and Depression scale (HADS)
timeFrame: Assessed at 180days
measure: Psychological function measured using Impact of Event Scale - Revised (IES-R)
timeFrame: Assessed at 180 days
measure: All-cause mortality
timeFrame: From date of randomisation up to 28 days
measure: Days alive and out of hospital according to survival status
timeFrame: From date of randomisation up to 180 days
measure: Days in hospital, rehabilitation facility or nursing home according to survival status
timeFrame: From date of randomisation up to 180 days
measure: Time from randomisation to ICU discharge
timeFrame: From date of randomisation up to 180 days
measure: Time from randomisation to hospital discharge
timeFrame: From date of randomisation up to 180 days
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St George Hospital
state: New South Wales
city: Sydney
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Mater Health
state: Queensland
city: Brisbane
country: Australia
facility: Mater Private Hospital
state: Queensland
city: Caboolture
country: Australia
facility: Caboolture Hospital
state: Queensland
city: Chermside West
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Redcliffe
country: Australia
facility: Redcliffe Hospital
state: Queensland
city: Rockhampton
country: Australia
facility: Rockhampton Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Geelong
country: Australia
facility: Geelong Hospital - Barwon Health
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Cabrini Health
state: Victoria
city: Melbourne
country: Australia
facility: Epworth Richmond
state: Victoria
city: Melbourne
country: Australia
facility: Western Health
state: Victoria
city: Prahran
country: Australia
facility: Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Hospital
state: Western Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Berlin
country: Germany
facility: The Charité
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Munich
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität Mϋnchen
city: Dublin
country: Ireland
facility: Beacon Hospital
city: Dublin
country: Ireland
facility: St Vincent's Hospital
city: Galway
country: Ireland
facility: Galway Hospital
city: Tallaght
country: Ireland
facility: Tallaght Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital (CVICU)
city: Auckland
country: New Zealand
facility: Auckland City Hospital (DCCM)
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital
city: Lewisham
country: United Kingdom
facility: University Hospital Lewisham
city: London
country: United Kingdom
facility: King's College Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
city: Swansea
country: United Kingdom
facility: Morriston Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Woolwich
country: United Kingdom
facility: Queen Elizabeth Hospital Woolwich
Study officials:
affiliation: ANZIC-RC
name: Carol Hodgson, Prof
role: STUDY_CHAIR
References:
citation: Hodgson CL, Bailey M, Bellomo R, Berney S, Buhr H, Denehy L, Gabbe B, Harrold M, Higgins A, Iwashyna TJ, Papworth R, Parke R, Patman S, Presneill J, Saxena M, Skinner E, Tipping C, Young P, Webb S; Trial of Early Activity and Mobilization Study Investigators. A Binational Multicenter Pilot Feasibility Randomized Controlled Trial of Early Goal-Directed Mobilization in the ICU. Crit Care Med. 2016 Jun;44(6):1145-52. doi: 10.1097/CCM.0000000000001643.
citation: Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med. 2017 Feb;43(2):171-183. doi: 10.1007/s00134-016-4612-0. Epub 2016 Nov 18.
citation: Iwashyna TJ, Hodgson CL. Early mobilisation in ICU is far more than just exercise. Lancet. 2016 Oct 1;388(10052):1351-1352. doi: 10.1016/S0140-6736(16)31745-7. No abstract available.
citation: TEAM Study Investigators and the ANZICS Clinical Trials Group; Hodgson CL, Bailey M, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Serpa Neto A, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Webb S, Young PJ. Early Active Mobilization during Mechanical Ventilation in the ICU. N Engl J Med. 2022 Nov 10;387(19):1747-1758. doi: 10.1056/NEJMoa2209083. Epub 2022 Oct 26.