Extracorporeal Membrane Oxygenation Physical Training

Study Overview
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Brief Summary
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Critically ill patients who require extracorporeal membrane oxygenation (ECMO) are the sickest in the hospital. More patients are surviving but survivors have compromised functional recovery for months or years. This trial aims to determine if early, physical training commenced within 48 hours of ECMO is feasible and improves muscle strength and functional status in patients compared to standard practice in a randomised controlled trial of 30 ICU patients.

Detailed Description
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The use of extracorporeal membrane oxygenation (ECMO) has expanded dramatically in Australia and globally. While life-saving in the short-term, it is typically associated with prolonged immobility and inflammation, which contributes to severe muscle weakness and wasting. Standard care delivers minimal physical training while patients remain on ECMO because standard care prioritises concerns about catheter dislodgement and cardio-respiratory strain. However, in other intensive care unit (ICU) conditions, techniques have been developed to allow early physical training in patients previously thought too unstable to be exercised, with important patient-centred and long-term cost-saving benefits. Our preliminary work shows that early individualised physical training is safe in ICU patients. A multicentre pilot study to establish feasibility in ECMO patients is urgently needed. The primary aim is to test the hypothesis that early, individualised, physical training (commenced within first 48 hours of ECMO) is feasible and improves functional recovery (the highest level of activity and duration). This has previously been reported to be associated with improved independent function at hospital discharge and discharge to home.1 The secondary aims are to test the hypothesis that early individualised physical training is (i) safe; (ii) improves muscle strength at day 7 and 10 and 20; and (iii) improves functional status (IMS) at day 7, 10 and 20 in ECMO patients relative to standard care. We are also aiming to describe the acute physiological effects of early physical training (commenced within 48hours of ECMO initiation) Respiratory and haemodynamic parameters, along with ECMO settings, will be recorded 30 minutes prior to each physical training session, during the session and 30 minutes post the training session. In addition, the range of values (min to max) for these parameters will be recorded for each 24hour period over the 7 days.

Official Title
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A Pilot Randomised Controlled Trial in Extracorporeal Membrane Oxygenation Physical Training (ECMO-PT)

Conditions
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Extracorporeal Membrane Oxygenation Complication, Critically Ill, Mechanically Ventilated

Intervention / Treatment
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* Behavioral: Early activity and Mobilisation intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults ≥ 18 years of age were physically independent prior to the current admission; receiving ECMO (veno-arterial or veno-venous) for at least 24 hours; clinician in charge of patient care has no objection to randomisation Exclusion Criteria: have been in ICU > 5 days prior to the commencement of ECMO; have received ECMO for more than 48 hours; in the opinion of the treating clinician, is not expected to recover in 90 days (e.g. intracerebral haemorrhage); whom death is expected within 24 hours; are unable to communicate in English

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A 30 patient, multicentre, randomised, trial of early individualised physical training compared to standard care.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early activity and Mobilisation intervention<br>Patients will be randomised within 48 hrs of commencing ECMO. Patients unable to initially receive active physical training will receive passive physical training for a minimum of 20 minutes and a maximum of one hour per day to maintain joint and muscle activity until active physical training is commenced. The intervention involves a progression of exercises with the objective of rehabilitating the patient at the highest level of exercise possible for the patient for the longest period of time that can be tolerated (up to 60 minutes) at each session, based on our published ICU mobility scale now used internationally in ICU trials. This is performed with or without IMV (including both endotracheal tubes or tracheostomies). | Behavioral: Early activity and Mobilisation intervention<br>* The early activity and mobilisation intervention is comprised of exercises based on a reproducible, physiological approach using both strength and functional activities<br>|
| No Intervention: Standard Care<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of delivering the intervention in the first 7 days after randomisation and the separation between the groups | Feasibility of delivering the intervention in the first 7 days after randomisation and the separation between the groups using the ICU mobility scale to report the highest level of activity. It is reported as median (IQR) over 7 days. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first stand out of bed | Time to first stand out of bed (within the first 28 days) | Within the first 28 days | 
| Incidence of Treatment-Emergent Adverse Events, Safety events (including decannulation of ventilator or ECMO cannula, fall to the floor during mobilization, desaturation SpO2 < 85%) at anytime during the first 7 days | Incidence of Treatment-Emergent Adverse Events, Safety events (including decannulation of ventilator or ECMO cannula, fall to the floor during mobilization, desaturation SpO2 < 85%) at anytime during the first 7 days | During the first 7 days | 
| Strength at day 7 and 10 | Strength at day 7 and 10 | Days 7 & 10 | 
| Function (reported as ICU mobility scale) measured at days 7, 10 and 20 | Function (reported as ICU mobility scale) measured at days 7, 10 and 20 | Days 7, 10 & 20 | 
| ICU and hospital length of stay | ICU and hospital length of stay (time from ICU admission to ICU and hospital discharge respectively censored at day 90) | Time from ICU admission to ICU and hospital discharge respectively censored at day 90 | 
| ICU and in-hospital mortality | ICU and in-hospital mortality (time from ICU admission to ICU and hospital discharge respectively censored at day 90) | Time from ICU admission to ICU and hospital discharge respectively censored at day 90 |