Treatment of Invasively Ventilated Adults With Early Activity and Mobilisation

NCT03133377 | Completed Phase 3 DMC

• 1 other identifier: TEAM U1111-1195-3567
• Study Type: interventional
• Target: 750
• Locations: 5 countries
• Sites: 49

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.

Conditions

Critically Ill, Mechanically Ventilated

Keywords

Early activity and mobilization, rehabilitation, intensive care

Outcome Measures

Primary Outcomes (1)

• Number of days alive and out of hospital

  Any days spent in rehabilitation or a nursing home counted as days in hospital

  between randomisation and 180 days

Secondary Outcomes (7)

• All-cause mortality

  From date of randomisation up to180days.

• Time from randomisation until death

  From date of randomisation unitl date of death from all cause, censored at 180days

• Ventilator-free days

  From date of randomisation until day 28

• ICU-free days

  From date of randomisation until day 28

• Quality of life and health status measured using the European Quality of Life 5 Dimensions 5 Level (EQ5D-5L)

  Assessed at 180days

Other Outcomes (9)

• Delirium free days

  From date of randomisation until day 28

• Cognitive function measured using Montreal Cognitive Assessment (MOCA-Blind)

  Assessed at 180days

• Psychological function measured using Hospital Anxiety and Depression scale (HADS)

  Assessed at 180days

Study Arms (2)

Early activity and Mobilisation intervention

EXPERIMENTAL

Patients will be assessed daily by an ICU physiotherapist using the ICU Mobility Scale (IMS) to determine the dosage and type of active exercises the patient will receive, using the early activity and mobilisation protocol. This protocol is hierarchical, with the objective of each intervention session beginning with the highest level of activity possible for the longest time possible, which then steps down to lower levels of activity if the patient fatigues. The intervention will be administered on all days in which the patient is admitted to ICU during the index hospitalisation, censored at 28days after.

Behavioral: Early activity and mobilisation

Standard of care

NO INTERVENTION

The control group will receive standard care from physiotherapy staff not involved in delivering the intervention. We have previously established that standard care in Australia for a patient receiving prolonged IMV (control group intervention) frequently involves no active exercise out of bed.

Interventions

Early activity and mobilisation BEHAVIORAL

The early activity and mobilisation intervention is comprised of exercises based on a reproducible, physiological approach using both strength and functional activities

Early activity and Mobilisation intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older.
• Intubated and expected to remain invasively mechanically ventilated the day after tomorrow.
• Sufficient cardiovascular stability to make mobilisation potentially possible, as indicated by:
• the absence of current brady-arrhythmia requiring pharmacological support
• a current ventricular rate ≤ 150 bpm
• most recent lactate ≤ 4.0 mmol/L
• 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.
• most recent cardiac index ≥ 2.0 L/min/m2 (where measured)
• no current requirement for VA ECMO
• Sufficient respiratory stability to make mobilisation potentially possible, as indicated by:
• current FiO2 ≤ 0.6
• current PEEP ≤ 16 cm H20
• an absence of current requirement for NO, prone ventilation, neuromuscular blockers, ventilation, prostacyclin, VV ECMO or HFOV
• current RR ≤ 45 bpm

You may not qualify if:

• Dependent for activities of daily living in the month prior to current ICU admission (gait aids are acceptable).
• Documented cognitive impairment.
• Proven or suspected acute primary brain pathology (e.g. traumatic brain injury, stroke, hypoxic brain injury).
• Proven or suspected spinal cord injury or other neuromuscular disease that will result in permanent or prolonged weakness (not including ICU acquired weakness).
• Has rest in bed orders and/or has bilateral non-weight bearing orders for the lower limbs.
• Life expectancy less than 180 days due to a chronic or underlying medical condition.
• 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.
• Unable to communicate in the official local language.
• This is not the first ICU admission in the index hospital admission.

Sponsors & Collaborators

• Australian and New Zealand Intensive Care Research Centre: lead
• National Health and Medical Research Council, Australia: collaborator
• ANZICS Clinical Trials Group: collaborator
• Medical Research Institute of New Zealand: collaborator
• Intensive Care National Audit & Research Centre: collaborator

Study Sites (49)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St George Hospital

Sydney, New South Wales, 2217, Australia

Location

John Hunter Hospital

Sydney, New South Wales, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Location

Mater Health

Brisbane, Queensland, Australia

Location

Mater Private Hospital

Brisbane, Queensland, Australia

Location

Caboolture Hospital

Caboolture, Queensland, Australia

Location

The Prince Charles Hospital

Chermside West, Queensland, Australia

Location

Redcliffe Hospital

Redcliffe, Queensland, Australia

Location

Rockhampton Hospital

Rockhampton, Queensland, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Launceston General Hospital

Launceston, Tasmania, Australia

Location

Geelong Hospital - Barwon Health

Geelong, Victoria, 3220, Australia

Location

St Vincent's Hospital Melbourne

Melbourne, Victoria, 3065, Australia

Location

Austin Health

Melbourne, Victoria, Australia

Location

Cabrini Health

Melbourne, Victoria, Australia

Location

Epworth Richmond

Melbourne, Victoria, Australia

Location

Western Health

Melbourne, Victoria, Australia

Location

Alfred Hospital

Prahran, Victoria, 3004, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

Royal Perth Hospital

Perth, Western Australia, Australia

Location

St John of God Hospital

Subiaco, Western Australia, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

The Charité

Berlin, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

Klinikum rechts der Isar der Technischen Universität Mϋnchen

Munich, Germany

Location

Beacon Hospital

Dublin, Ireland

Location

St Vincent's Hospital

Dublin, Ireland

Location

Galway Hospital

Galway, Ireland

Location

Tallaght Hospital

Tallaght, Ireland

Location

Auckland City Hospital (CVICU)

Auckland, New Zealand

Location

Auckland City Hospital (DCCM)

Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

Tauranga Hospital

Tauranga, New Zealand

Location

Wellington Hospital

Wellington, New Zealand

Location

Bristol Royal Infirmary

Bristol, United Kingdom

Location

Frimley Park Hospital

Frimley, United Kingdom

Location

University Hospital Lewisham

Lewisham, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Royal Berkshire Hospital

Reading, United Kingdom

Location

Morriston Hospital

Swansea, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Queen Elizabeth Hospital Woolwich

Woolwich, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 26968024 BACKGROUND

• 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.

  PMID: 27864615 BACKGROUND

• 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.

  PMID: 27707476 BACKGROUND

• Higgins AM, Lee YY, Bailey M, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Hurford S, Iwashyna TJ, Serpa Neto A, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Webb S, Young PJ, Hodgson CL; Treatment of Mechanically Ventilated Adults With Early Activity and Mobilization (TEAM) Study Investigators. The Cost-Effectiveness of Early Active Mobilization During Mechanical Ventilation in the ICU: An Economic Evaluation Alongside the Treatment of Mechanically Ventilated Adults With Early Activity and Mobilization (TEAM) Trial. Crit Care Med. 2025 Sep 1;53(9):e1725-e1735. doi: 10.1097/CCM.0000000000006715. Epub 2025 May 27.

  PMID: 40439527 DERIVED

• Broadley T, Serpa Neto A, Bailey M, Bellomo R, Brickell K, Buhr H, Gabbe BJ, Gould DW, Harrold M, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Webb S, Young PJ, Higgins AM, Hodgson CL; TEAM Trial Investigators. Adverse events during and after early mobilisation: A post hoc analysis of the TEAM trial. Aust Crit Care. 2025 May;38(3):101156. doi: 10.1016/j.aucc.2024.101156. Epub 2025 Jan 17.

  PMID: 39826257 DERIVED

• Presneill JJ, Bellomo R, Brickell K, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna T, Neto AS, Nichol A, Schaller SJ, Sivasuthan J, Tipping C, Webb S, Young P, Hodgson CL; TEAM Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Protocol and statistical analysis plan for the phase 3 randomised controlled Treatment of Invasively Ventilated Adults with Early Activity and Mobilisation (TEAM III) trial. Crit Care Resusc. 2023 Oct 18;23(3):262-272. doi: 10.51893/2021.3.OA3. eCollection 2021 Sep 6.

  PMID: 38046085 DERIVED

• 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.

  PMID: 36286256 DERIVED

Related Links

• TEAM study website

MeSH Terms

Conditions

Critical Illness; Motor Activity

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Carol Hodgson, Prof

  ANZIC-RC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 28, 2017
• Study Start: February 28, 2018
• Primary Completion: May 18, 2022
• Study Completion: November 10, 2022
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (28); DE (3); GB (9); NZ (5); IE (4)