Investigating the Safety of Mobilising Intensive Care Unit Patients Receiving Vasoactive Drugs: An Exploratory Observational Study
Conditions: Critical Illness
Sponsor: Imperial College London

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 1 of 34 
IRAS Project ID: 251112 
 
 
 
Investigating the safety of mobilising 
intensive care unit patients receiving 
vasoactive drugs: An exploratory 
observational study  
 
 
 
 
Version 3, 20/05/2019 
 
 
NCT03869541 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 2 of 34 
IRAS Project ID: 251112 
 
 
 
 
 
 
 
 
 
 
Investigating the safety of mobilising 
intensive care unit patients receiving 
vasoactive drugs: An exploratory 
observational study  
 
 
 
 
Version 3, 20/05/2019 
 
 
 
 
MAIN SPONSOR: Imperial College London 
FUNDERS: Health Education England / National Institute for Health Research 
STUDY COORDINATION CENTRE: Imperial College London 
 
IRAS Project ID: 251112 
REC reference: 18/WA/0310 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
Professor Anthony 
Gordon, Chief Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 3 of 34 
IRAS Project ID: 251112 
Study Management Group 
 
Chief Investigator: Prof Anthony Gordon 
 
Co-investigators: Huw Woodbridge, Prof Stephen Brett, Dr Caroline Alexander 
 
Statistician: Not applicable 
 
Study Management: Huw Woodbridge 
 
 
Study Coordination Centre  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator: Huw Woodbridge 
Address: Rooms 5.03 and 5.08, 5th floor Medical School Building, Imperial College London, St 
Marys Hospital, Norfolk Place, London, W2 1PG  
 
 
 
 
 
Tel: 07714051401 
 
 
 
 
 
 
 
E-mail:  h.woodbridge@imperial.ac.uk 
 
 
 
 
 
 
 
 
 
Clinical Queries 
 
Clinical queries should be directed to huw.woodbridge@nhs.net who will direct the query to the 
appropriate person 
 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study.  For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 9459/ 0207 594 1862 
http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice  
 
Funder 
 
Health Education England / National Institute for Health Research 
 
 
 
 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 4 of 34 
IRAS Project ID: 251112 
This protocol describes this study and provides information about procedures for entering participants.  Every 
care was taken in its drafting, but corrections or amendments may be necessary. These will be circulated to 
investigators in the study.  Problems relating to this study should be referred, in the first instance, to the Chief 
Investigator.  
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for Health and 
Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data Protection Act and other 
regulatory requirements as appropriate.  
 
Table of Contents                                                               
       Page No 
1. 
INTRODUCTION .................................................................................................................... 7 
1.1 
BACKGROUND ................................................................................................................................................7 
1.2 
RATIONALE FOR CURRENT STUDY ..................................................................................................................7 
2.  STUDY OBJECTIVES ..................................................................................................................... 9 
3.  STUDY DESIGN .......................................................................................................................... 10 
3.1 STUDY SETTING ................................................................................................................................................... 12 
4. 
PARTICIPANT ENTRY ........................................................................................................... 12 
4.1 
PRE-REGISTRATION EVALUATIONS ............................................................................................................... 12 
4.2 
INCLUSION CRITERIA .................................................................................................................................... 12 
4.2.1 Patient participants ............................................................................................................................................ 12 
4.2.2 
Clinician participants in the survey on acceptability of randomisation.......................................................... 12 
4.2.3 Clinician participants in the survey on feasibility of adverse event tool ............................................................ 12 
4.3 
EXCLUSION CRITERIA .................................................................................................................................... 13 
4.3.1 Patient participants ............................................................................................................................................ 13 
4.3.2 Clinician participants in either the survey on acceptability of randomisation or the survey on feasibility of 
adverse event tool ....................................................................................................................................................... 13 
4.4 
WITHDRAWAL CRITERIA ............................................................................................................................... 13 
5. 
STUDY PROCEDURES ........................................................................................................... 13 
5.1 
 PARTICIPANT RECRUITMENT DATA ............................................................................................................. 13 
5.2  
DEMOGRAPHIC DATA ................................................................................................................................... 14 
5.3  
KEY OUTCOMES............................................................................................................................................ 14 
5.4  
SURVEY ........................................................................................................................................................ 15 
5.4.1 Patient/consultee survey .................................................................................................................................... 15 
5.4.2 Clinician survey ................................................................................................................................................... 16 
5.5 
ANALYSIS OF MOBILISATION ........................................................................................................................ 16 
5.6  
ASSESSMENT OF DAY 60 OUTCOMES ........................................................................................................... 18 
5.7  
END OF STUDY ............................................................................................................................................. 20 
6. 
SAMPLE SIZE ....................................................................................................................... 20 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 5 of 34 
IRAS Project ID: 251112 
6.1 PATIENT PARTICIPANTS ...................................................................................................................................... 20 
6.2 CLINICIAN PARTICIPANTS IN THE SURVEY ON ACCEPTABILITY OF RANDOMISATION .......................................... 21 
6.3 CLINICIAN PARTICIPANTS IN THE SURVEY ON FEASIBILITY OF THE ADVERSE EVENT TOOL .................................. 21 
7. 
ADVERSE EVENTS ................................................................................................................ 21 
7.1 
DEFINITIONS ................................................................................................................................................ 21 
7.2 
REPORTING PROCEDURES ............................................................................................................................ 22 
7.2.1 Non serious AEs .................................................................................................................................................. 22 
7.2.2 Serious AEs ......................................................................................................................................................... 22 
8. 
STATISTICS AND DATA ANALYSIS ......................................................................................... 23 
9. 
REGULATORY ISSUES .......................................................................................................... 23 
9.1 
ETHICS APPROVAL ........................................................................................................................................ 23 
9.2 
CONSENT ...................................................................................................................................................... 24 
9.2.1 Identification of potential participants ............................................................................................................... 24 
9.2.2 Approaching potential participants .................................................................................................................... 24 
9.2.3 Informed consent from the patient .................................................................................................................... 25 
9.2.4 Consultee advice ................................................................................................................................................. 26 
9.2.5 Retrospective consent from the patient............................................................................................................. 26 
9.2.6 Clinician recruitment for survey on acceptability of randomisation .................................................................. 27 
9.2.7 Clinician recruitment for survey on feasibility of adverse event tool ................................................................. 27 
9.3 
CONFIDENTIALITY......................................................................................................................................... 28 
9.3.1 Initial data collection .......................................................................................................................................... 28 
9.3.2 Analysis of data ................................................................................................................................................... 28 
9.3.3 Long-term storage of data .................................................................................................................................. 29 
9.4 
INDEMNITY .................................................................................................................................................. 29 
9.5 
SPONSOR ..................................................................................................................................................... 29 
9.6 
FUNDING ...................................................................................................................................................... 29 
9.7 
AUDITS ......................................................................................................................................................... 30 
10. 
STUDY MANAGEMENT ........................................................................................................ 30 
11. 
PUBLICATION POLICY .......................................................................................................... 30 
12. 
REFERENCES ....................................................................................................................... 30 
 
GLOSSARY OF ABBREVIATIONS 
6MWT 
6-Minute Walk Test  
AE 
Adverse event 
APACHE II 
Acute physiology and chronic health evaluation II 
ICU 
Intensive care unit 
IMS 
ICU Mobility Scale 
RASS 
Richmond Agitation-Sedation Scale 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 6 of 34 
IRAS Project ID: 251112 
RCT 
Randomised controlled trial 
SAE 
Serious adverse event 
SF-36 v2 
36-item Short Form Health Survey Version 2  
SOFA 
Sequential Organ Failure Assessment 
RAND SF-
36 v1 
RAND 36-Item Health Survey 1.0 Questionnaire 
WHODAS 
2.0 
World Health Organisation’s Disability Assessment Schedule 
2.0 
 
KEYWORDS 
Early Ambulation; Critical Care 
Intensive Care; Patient Safety 
Vasoactive drugs 
 
 
 
 
 
STUDY SUMMARY 
 
  
TITLE Investigating the safety of mobilising intensive care unit patients receiving 
vasoactive drugs: An exploratory observational study 
DESIGN Exploratory observational study 
AIMS 1. To describe current practice in one healthcare organisation of mobilising 
ICU patients receiving vasoactive drugs. 
2. To describe the preliminary feasibility of measuring the safety of mobilising 
ICU patients receiving vasoactive drugs. 
OUTCOME MEASURES Key outcomes include: Hypothetical recruitment rate for a future randomised 
controlled trial; follow-up rate of participants for day-60 outcomes. 
POPULATION Adult patients admitted to the intensive care units. 
ELIGIBILITY For patient participants:  
Inclusion criteria: Patients admitted to the ICU who are receiving vasoactive 
drugs; age greater than or equal to 18 years old; expected to remain admitted 
to the ICU for at least 24 hours post-enrolment. 
Exclusion criteria: Patient expected to die imminently; mobilisation is 
contraindicated by the nature of patients existing injuries; where it is clear from 
the medical records that participants are prisoners or offenders on probation; 
patient and/or their consultee is unable to speak English; patients with 
neuromuscular disease or acute brain injury or spinal cord injury. 
DURATION 01/11/2018 – 09/08/2019 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 7 of 34 
IRAS Project ID: 251112 
 
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
 
Muscle wasting in an intensive care unit (ICU) population is a considerable concern as it has been 
found to be fast-developing during an ICU admission (Puthucheary et al., 2013). Muscle weakness 
extends substantially beyond an ICU stay and is associated with deficits in physical functioning 
and quality of life (Fan et al., 2014). These deficits are known to be long term (Dowdy et al., 2006) 
having been demonstrated five years after an ICU stay (Herridge  et al., 2011). These long-term 
complications have also been associated with increased healthcare costs (Lone et al., 2016). 
Early mobilisation as part of physical rehabilitation has been recommended as a strategy to help 
address these poor physical outcomes and is advocated in several practice guidelines for ICUs 
(NICE, 2009, Girard et al., 2017). Early mobilisation is mobilisation occurring whilst the patient is 
still on the ICU (Bailey et al., 2007). Examples of mobilisation can include: 
‘turning and moving in bed, active-assisted and active exercise, use of cycling pedals in bed, 
sitting over the edge of the bed, standing, stepping in place, transferring from the bed or 
chair, chair exercises and walking’ (Gosselink et al., 2008, p. 1190). 
The evidence base for early mobilisation has developed substantially (Connolly et al., 2016), with 
a recent increase in the number of randomised clinical trials (Wright et al., 2018, Morris et al., 
2016, Schaller et al., 2016, Moss et al., 2015, Denehy et al., 2013, Schweickert et al., 2009). 
These have demonstrated beneficial effects for ICU patients such as improved ability to mobilise 
(Schaller et al., 2016), less delirium (Schweickert et al., 2009) and a decreased length of stay 
(Schaller et al., 2016). Furthermore, these benefits of improved mobility and function have 
continued to be measured at discharge from hospital (Schaller et al., 2016, Schweickert et al., 
2009). Indeed, six months after critical illness, meta-analysis has demonstrated an increased 
amount of days out of hospital (Tipping et al., 2017). Early mobilisation is also regularly reported 
as being safe with low rates of adverse events recorded (Nydahl et al., 2017, Sricharoenchai et al., 
2014, Bailey et al., 2007, Stiller et al., 2004). 
 
1.2 
RATIONALE FOR CURRENT STUDY 
 
Trials of early ICU mobilisation have shown mixed results to date, with some studies concluding no 
evidence of beneficial effect of mobilisation on short term outcomes (Denehy et al., 2013, Morris et 
al., 2016, Moss et al., 2015) and limited long-term beneficial effects (Wright et al., 2018, Morris et 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 8 of 34 
IRAS Project ID: 251112 
al., 2016, Denehy et al., 2013, Moss et al., 2015). Further, concern remains over potential adverse 
outcomes resulting from physical rehabilitation interventions on intensive care. Firstly this has arisen 
from a non-statistically significant increase in mortality demonstrated in a recent meta-analysis 
(Tipping et al., 2017) requiring further investigation (Cuthbertson and Goddard, 2017). Secondly 
there are methodological limitations in previous studies, which include a wide variety of defining 
adverse event criteria (Nydahl et al., 2017), a lack of recording of adverse events (Connolly et al., 
2016) and concerns around the heterogeneous population in an ICU and whether safety differs for 
each individual (Tipping et al., 2017). Therefore measuring the relative benefits and harms of early 
mobilisation in different subgroups of the ICU population is a current research priority (Connolly et 
al., 2016, Cuthbertson and Goddard, 2017, Parry et al., 2018) 
 
One subgroup of interest are those patients receiving vasoactive drugs, such as inotropes (drugs 
aiding contraction of the myocardium) and vasopressors (drugs that constrict the blood vessels to 
help maintain blood pressure) (Bangash et al., 2012). If a patient requires vasoactive drugs to 
maintain cardiovascular stability, there may be more risk of adverse events occurring during 
mobilisation because there is less cardiovascular reserve to cope with the demands of exercise 
(Stiller and Phillips, 2003). The evidence for the safety of early ICU mobilisation with patients who 
are receiving vasoactive drugs consists of limited observational data (Rebel et al., 2018, Boyd et 
al., 2018, Hickmann et al., 2016, Nievera et al., 2016). The current evidence is insufficient to 
accurately guide clinicians to know when it is safe to start mobilising this patient group. 
 
Greater understanding is required, therefore there is a need for a future randomised controlled trial 
(RCT) answering the question ‘Is it safe to mobilise ICU patients receiving vasoactive drugs? 
However, before a robust trial can be designed, a study is required to address several uncertainties. 
To address these uncertainties, it is proposed to carry out an exploratory observational study to 
prepare to investigate the safety of mobilising ICU patients receiving vasoactive drugs.  
 
This protocol presents phase two of this study, which aims to clarify uncertainties such as potential 
recruitment and follow-up rate. Additionally, clarification is required as to when clinicians are 
uncertain about mobilising ICU patients receiving vasoactive drugs. Further, although there is a 
substantial argument for the existence of equipoise in the literature, it is not known whether clinicians 
and patients are personally convinced of this equipoise to the extent that randomisation of patients 
in a clinical trial would be acceptable. Finally, information is required to inform the choice of a suitable 
primary outcome measure that adequately measures the effects of mobilisation in this group.  
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 9 of 34 
IRAS Project ID: 251112 
2.  STUDY OBJECTIVES 
 
Primary objective 1  
To describe current practice in one healthcare organisation of mobilising ICU patients 
receiving vasoactive drugs. 
Secondary objectives 
1. To measure the mobilisation that occurs while patients receive vasoactive drugs in terms of 
the type of mobilisation and type and dosage of vasoactive drugs.  
2. To describe which patients receiving vasoactive drugs are not mobilised and the reasons 
why.  
3. To measure the adverse event rate occurring in patients mobilised on vasoactive drugs. 
4. To describe how clinicians judged the risk of mobilising patients receiving vasoactive 
drugs.  
5. To measure what standard care is in relation to mobilisation treatment milestones. 
6. To measure cost of care related to ICU and hospital length of stay and mobilisation 
received. 
Primary objective 2  
To describe the preliminary feasibility of measuring the safety of mobilising ICU patients 
receiving vasoactive drugs. 
 
Secondary objectives 
 
2 a) Recruitment 
 
1. To measure the number of patients who would consent in principle to be recruited into an 
RCT on the safety of mobilising patients receiving vasoactive drugs and to describe the 
reasons why patients would not consent.  
2. To understand the acceptability to patients and clinicians, of randomising patients receiving 
vasoactive drugs to an intervention or control arm in a future RCT on the safety of 
mobilising patients receiving vasoactive drugs.  
3. To test the feasibility of clinicians and clinician researchers taking informed consent from 
patients or their consultees on ICU. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 10 of 34 
IRAS Project ID: 251112 
2 b) Sample size 
1. To measure mortality, disability, physical functioning and health related quality of life 
outcome measures of ICU patients to inform a future sample size calculation. 
2 c) Outcomes 
1. To describe the feasibility of measuring mortality, physical functioning, disability and health 
related quality of life outcomes to inform a future primary outcome choice. 
2. To measure whether an adverse event tool captures all unsafe events that occur during or 
immediately after early mobilisation of adult intensive care patients receiving vasoactive 
drugs.  
3. To describe the feasibility of an adverse event tool, during clinical practice by ICU clinicians 
and retrospectively by researchers.  
 
3.  STUDY DESIGN 
 
This study is phase two of a two phase feasibility, where phase one (IRAS 251108) is a review of 
current practice (figure 1).   
 
This study (phase two) will recruit ICU patients to measure preliminary feasibility outcomes using a 
survey, analysis of mobilisation treatments and assessment outcomes at day 60 post-enrolement.  
 
a) Firstly clinicians and patients or their consultees will be surveyed about the acceptability of 
recruitment and randomisation into an RCT. In addition we will measure the feasibility of 
collecting baseline data on pre-admission function, frailty and comorbidities.  
b) Secondly, we will analyse routine mobilisation treatments of patients receiving vasoactive 
drugs to describe clinician’s reasons for judging whether it was safe to mobilise and the 
feasibility of a new adverse event tool. 
c) Finally, we will describe the feasibility of measuring outcomes at day 60 to inform the 
selection of a primary outcome measure. 
 
The duration of this study will be from 01/11/2018 – 09/08/2019.  
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 11 of 34 
IRAS Project ID: 251112 
 
 
 
 
 
 
 
 
Figure 1: Outline of feasibility study. 
 
ICU: Intensive Care Unit; rehab: rehabilitation; AE: adverse event;  SAE: serious adverse event.
Case note review
• Patients eligible for 
recruitment
• Patient trajectories on 
ICU:
• When receiving 
vasoactive drugs
• Mobilisation 
occuring on 
vasoactive drugs
2 a) Survey
• Patient/consultee:
• Acceptability of:
• Recruitment 
• Randomisation
• Baseline outcomes
• Clinicians:
• Acceptability of 
randomisation
2 b) Analysis of 
mobilisation
• Clinician judgement of 
safety for mobilising.
• ICU rehab. AE tool:
• Researcher and 
clinician 
measurement.
• Compared against 
SAE’s
• Feasibility
2 c) Assessment 
of 60 day 
outcomes
• Candidate primary 
outcomes
• Feasibility of 
measurement. 
Phase 1: Observation of current practice 
Phase 2: Additional patient analysis 
 
 
During ICU stay 
Day 60 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 12 of 34 
IRAS Project ID: 251112 
3.1 STUDY SETTING 
 
This study will be based at the intensive care units at Imperial College Healthcare NHS Trust. 
Follow up at day 60 will be coordinated through Imperial College Healthcare NHS Trust (e.g. for 
telephone questionnaires), with assessment of performance-based outcomes occurring at Imperial 
College Healthcare NHS Trust.  
 
4. 
PARTICIPANT ENTRY 
 
Current ICU clinical records will be screened for inclusion and exclusion criteria as set out below. 
Any uncertainties will be clarified in discussion with other members of the clinical team.  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
 
 
No additional screening procedures will need to be carried out before participants enter the study.  
 
4.2 
INCLUSION CRITERIA 
 
4.2.1 Patient participants 
 
• 
Patients admitted to the ICU who are receiving vasoactive drugs: Patients receiving vasoactive 
drugs are the group of interest for the potential future RCT. 
• 
Age greater than or equal to 18 years old. 
• 
Expected to remain admitted to the ICU for at least 24 hours post-enrolment to allow potential 
for mobilisation to occur.  
 
4.2.2 Clinician participants in the survey on acceptability of randomisation 
 
• 
Clinicians who work in the intensive care unit where a patient participant has been 
admitted. These clinicians will be answering a survey about a recently recruited patient 
participant. 
 
4.2.3 Clinician participants in the survey on feasibility of adverse event tool 
 
• 
An ICU clinician at the research site. 
• 
Has used the ICU physical rehabilitation adverse event tool as part of this research study. 
 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 13 of 34 
IRAS Project ID: 251112 
4.3 
EXCLUSION CRITERIA 
 
4.3.1 Patient participants 
 
• 
We will exclude any patient who is expected to die imminently, as per clinical opinion.  
• 
We will exclude any patient where mobilisation is contraindicated by the nature of their existing 
injuries.  
• 
Where it is clear from the medical records that participants are prisoners or offenders on 
probation. This is because of the additional ethical implications of including these patients. 
• 
Patients with neuromuscular disease or acute brain injury or spinal cord injury. Exclusion of 
this group is firstly because early rehabilitation of stroke patients is associated with worse 
outcomes (Avert Group, 2015, Cuthbertson and Goddard, 2017) and secondly because 
mobilisation of these patients is much more complex. 
• 
If the patient and/or their consultee is unable to speak English. Spoken English is required for 
consent and outcome measurement and there is not provision for an interpreter. 
 
4.3.2 Clinician participants in either the survey on acceptability of randomisation or the 
survey on feasibility of adverse event tool 
 
No exclusion criteria.  
 
 
4.4 
WITHDRAWAL CRITERIA 
 
If participants withdraw their consent, we will not collect further data about them. We will ask the 
participant’s permission for data already collected to be kept and used in the analysis.  
 
 
5. 
STUDY PROCEDURES 
 
The main data sources will include the routinely collected clinical data contained within the NHS 
Trust systems, data provided by the participant/their consultee/proxy and data provided by 
clinicians. Further details and other data sources are outlined below. 
 
5.1 
 PARTICIPANT RECRUITMENT DATA 
 
ICU patients will be recruited as set out elsewhere in this protocol and data about recruitment will 
be collected:  

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 14 of 34 
IRAS Project ID: 251112 
• 
Standard recruitment data that records the numbers of individuals at the different stages of 
the study (for example numbers eligible, numbers excluded) and any reason for not taking 
part at each stage. This will also include details about any consultee advice given. 
• 
Data to inform which research staff will be required for future recruitment of patients in the 
RCT will be collected by measuring the number of participants recruited by the clinicians 
(physiotherapists, doctors or nurses), research nurses or clinician researchers. 
• 
Whether the participant was enrolled before the first mobilisation session has occurred to 
measure whether this is feasible and the day of ICU stay that consent was obtained.  
 
For each participant enrolled, the following procedures will be carried out (figure 1). In addition, for 
important feasibility outcomes, we have specified feasibility ‘success’ criteria which are an 
indication to consider future investigation of the mobilisation of patients receiving vasoactive 
drugs. If these criteria are not met, then further consideration is required before deciding whether 
future investigation of mobilisation of this patient group is needed. 
 
5.2  
DEMOGRAPHIC DATA  
 
Baseline data will be collected for all participants included in the study in order to provide 
information on the characteristics of patients potentially eligible for a future RCT. This data will be 
used to describe baseline characteristics (for example age, gender), characteristics of ICU 
admission (for example reason for admission, APACHE (Acute physiology and chronic health 
evaluation) II score (Knaus et al., 1985), SOFA (Sequential Organ Failure Assessment) score 
(Vincent et al., 1998), and the length of time receiving mechanical ventilation and/or non-invasive 
ventilation. Contact details of the patient and next of kin will be recorded to facilitate day 60 follow-
up.  
 
5.3  
KEY OUTCOMES 
 
Key outcomes for this exploratory study are: 
• 
Hypothetical recruitment rate for the future RCT. 
• 
Follow-up rate of participants for day-60 outcomes. 
 
More details about these outcomes, plus the secondary outcomes for this study are detailed 
below. 
 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 15 of 34 
IRAS Project ID: 251112 
5.4  
SURVEY 
 
5.4.1 Patient/consultee survey  
 
Once a patient has been recruited into the feasibility study, a short survey will be carried out with 
the patient, or consultee if they were the one to give ‘consent’ on behalf of the patient. For a full list 
of the questions / the form where the information will be logged, please see the ‘Patient participant 
initial survey Case Report Form’. Firstly they will be presented with a summary of the future RCT 
plus three randomisation scenarios for patients receiving vasoactive drugs: (1) early physical 
rehabilitation or no rehabilitation; (2) early physical rehabilitation or standard care; or (3) 
‘protocolised care’ (where the decision to mobilise is based on a pre-defined risk stratification 
protocol – based on the results of the results of a previous Delphi study (IRAS project ID: 212066; 
REC reference: 17/LO/0830)) or standard care. The following outcomes will then be assessed: 
 
• 
Acceptability of hypothetical recruitment into the future RCT. This will be measured by a 
hypothetical recruited rate for the future RCT. Reasons why patients would not consent will 
also be collected. Feasibility ‘success’ is defined as two patients per ICU per month 
(Hodgson et al., 2016) 
• 
Acceptability of hypothetical randomisation into the RCT. This will be measured by the 
number of feasibility participants who would accept the randomisation scenarios described 
above and the reasons for their decisions. 
 
Recent evidence has shown how comorbidities (Puthucheary and Denehy, 2015), pre-morbid 
frailty (Muscedere et al., 2017, Ferrante et al., 2018) and physical function/disability (Ferrante et 
al., 2015, Biehl et al., 2015) influence long-term physical outcomes and mortality after an ICU 
admission. As a result, the importance of recording this data for trial participants has been 
emphasised to ensure that groups are comparable (Azoulay et al., 2017, Connolly and Denehy, 
2018). Therefore as part of the above survey, patient co-morbidities (for example using the 
Functional Comorbidity Index (Groll et al., 2005) and the Charlson Comorbidity Index (Charlson et 
al., 1987)), pre-morbid frailty (for instance using the Clinical Frailty Scale (Pugh et al., 2018, 
Rockwood et al., 2005)) and physical functioning (for example using the World Health 
Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-item or 12-item version 
(Ustun et al., 2010)) will be measured. The feasibility of measuring baseline comorbidities, frailty 
and physical functioning through patient or consultee (proxy) reporting or through information 
contained in the case notes will then be measured by the number of completed outcomes for each 
patient recruited into the feasibility study. Feasibility ‘success’ is defined as completing the above 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 16 of 34 
IRAS Project ID: 251112 
outcomes for 98% of participants. The time point that the above information is collected will also 
be recorded.  
 
5.4.2 Clinician survey 
 
For each patient recruited into the feasibility study, ICU clinicians (consultant doctor in charge, 
nurse in charge and the senior physiotherapist following recruitment) will be presented with a brief 
outline of the future RCT as well as the randomisation scenarios outlined above. This will occur ad 
hoc on the ICU following recruitment. For a full list of the questions / the form where the 
information will be logged, please see the ‘Clinician survey on acceptability of randomisation Case 
Report Form’. The following outcome will be measured:  
 
• 
Acceptability of hypothetical randomisation into a future RCT. This will be measured by the 
number of clinicians who would accept the randomisation scenarios described above for 
each patient recruited into the feasibility study, and the reasons for their decisions. 
Feasibility success is if 80% of participants are acceptable to be randomised (in whichever 
scenario). The time point that the clinicians are asked will also be recorded. 
 
5.5 
ANALYSIS OF MOBILISATION 
 
Whenever a physiotherapist reviews a patient recruited into the feasibility study for potential 
physical rehabilitation whilst they are receiving vasoactive drugs, they will complete an extra 
proforma in the case notes. This will record the following data to provide information on the 
decision-making process on the readiness of a patient to mobilise and the feasibility of using an 
adverse event tool: 
 
• 
Who made the final decision whether to mobilise the patient and the reasons for the 
decision. 
• 
Was the presence of vasoactive drugs a factor in the decision of whether to mobilise, either 
from the perspective of clinicians or in discussion with the patient/family/carers 
themselves? 
• 
If a mobilisation treatment is carried out the following will also be completed: 
o The reasons why the mobilisation treatment was stopped. This is measured to 
capture clinicians perceived risk thresholds for discontinuing mobilisation. This 
informs the measurement of the usability of the adverse event tool. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 17 of 34 
IRAS Project ID: 251112 
o An ICU physical rehabilitation adverse event tool used to measure adverse events 
that occur during or immediately after the mobilisation treatment. This is a new 
adverse event tool developed by the authors using an international, expert 
consensus Delphi process (IRAS project ID: 212066; REC reference: 17/LO/0830). 
The tool outlines specific adverse events including cardiovascular, respiratory, 
neurological, airway, attachments, falls and injury related events agreed as 
important to record when measuring the safety of ICU mobilisation. 
o The approximate time taken to complete the adverse event tool to inform the 
assessment of its feasibility. Feasibility success is defined as less than 5 minutes  
 
Alongside this, a case note review will be completed by the research team for each mobilisation 
treatment of patients receiving vasoactive drugs enrolled into the feasibility study. The researcher 
will record ICU physical rehabilitation adverse events and serious adverse events that occur 
during or immediately after mobilisation treatment. The following outcomes will then be measured: 
 
• 
ICU rehabilitation adverse event rate and SAE rate. SAEs will be measured during the note 
review and as reported by clinicians and researchers during the study as part of the 
mandated safety reporting. This will highlight the most efficient way to collect SAEs and 
both measures will inform a description of the safety of usual care. 
• 
Description of the number and type of rehabilitation adverse events and serious adverse 
events. Recorded to measure whether the rehabilitation AE tool is fit for purpose and able 
to capture all unsafe events that occur in this population of patients mobilising on 
vasoactive drugs.  
• 
Description of number and type of rehabilitation adverse events recorded prospectively by 
the treating clinician and retrospectively by researcher case note review. This data will 
provide information on the usability of the tool and the most feasible way to record AE’s in 
future research.  
• 
Loss of information that occurs when the ICU rehabilitation AE tool is completed by 
clinicians and researchers will also be recorded to provide feasibility data. For clinicians 
this will be assessed by the number of mobilisation treatments on vasoactive drugs 
occurring in patients recruited into the feasibility study where the rehabilitation adverse 
event tool is not completed or incomplete. For researchers, this will be assessed by the 
number of mobilisation treatments on vasoactive drugs where the researcher was unable 
to complete tool using the information available in the case notes. Feasibility success is 
less than or equal to 10% loss of information. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 18 of 34 
IRAS Project ID: 251112 
 
Towards the end of the data collection period for patients on ICU, a short survey will be carried out 
of clinicians who completed the ICU rehabilitation adverse event tool. This survey will ask about 
the usability and feasibility of completing the AE tool in the context of clinical practice. 
 
In addition to the above, the following data will be recorded for participants to further quantify 
standard care:  
• 
Amount of time the patient received vasoactive drugs during the admission. 
• 
Mobilisation occurring whilst patients are receiving vasoactive drugs, for example, by: 
o Number of patients who are mobilised whilst receiving vasoactive drugs.  
o Number of mobilisation treatment sessions on vasoactive drugs. 
o Number of days on vasoactive drugs where mobilisation treatment occurred.  
o Highest level of mobilisation achieved in each treatment session using the ICU 
Mobility Scale (IMS) (Hodgson et al., 2014a, Tipping et al., 2016). 
o Type and dose of vasoactive drugs patient received during mobilisation treatment. 
• 
Patients receiving vasoactive drugs who are not mobilising, for example, by: 
o Number of days receiving vasoactive drugs where mobilisation is not occurring. 
o On these days, any documented reasons for not mobilising.  
 
The following outcomes will be used to describe standard care, for potential use as surrogate 
outcomes in a future pilot trial or feasibility study: 
• 
Time to first mobilisation treatment and whether this first mobilisation treatment occurred 
whilst the patient was still receiving vasoactive drugs. 
• 
Time to first being able to sit out of bed, stand and walk (regardless of the assistance 
required) (Nickels et al., 2017, TEAM Study Investigators et al., 2015). 
• 
ICU Mobility Scale (IMS) level at ICU discharge.  
• 
ICU and hospital length of stay.  
 
 
5.6  
ASSESSMENT OF DAY 60 OUTCOMES 
 
To inform the future choice of suitable primary outcome measure for the future RCT, we will 
describe the feasibility of measuring candidate primary outcome measures at day 60 post-
enrolment in the study. Data from outcome measurement will also inform a future sample size 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 19 of 34 
IRAS Project ID: 251112 
calculation. The following outcomes will be recorded as soon as possible after day 60 post-
enrolment.  
• 
Mortality:  
Alive/deceased status will be recorded including date of death. This will be confirmed using 
clinical data contained within the NHS Trust systems, from NHS Spine (a national database 
held by NHS Digital, but accessible within the research sites to research nurses), or 
contacting the participant’s GP to clarify any uncertainty. The GP will be informed that the 
participant has been enrolled in the study after consent is taken and will be sent a copy of 
the participant information sheet. If no date of death is recorded, the participant will be 
contacted to measure the other outcome measures below. If at this point it is discovered 
that the participant is no longer alive, then date of death will be recorded as informed by 
relatives/carers. 
• 
Health-related quality of life: 
Measured using the EQ - 5D (5 Level) questionnaire (EQ-5D-5L) (EuroQol, 1990, Herdman 
et al., 2011, Janssen et al., 2013). 
• 
Disability: 
Measured using the World Health Organisation’s Disability Assessment Schedule 2.0 
(WHODAS 2.0) 36-item or 12-item version (Hodgson et al., 2017, Ustun et al., 2010).  
• 
Physical functioning: 
Because they have been shown to measure different components of physical functioning 
(Denehy et al., 2014), this domain will be measured using a patient-reported outcome 
measure (for example the physical function domain of the 36-item Short Form Health 
Survey Version 2 (SF-36 v2) (Ware, 2000, McDowell et al., 2017) or the physical function 
domain of the RAND 36-Item Health Survey 1.0 Questionnaire (RAND SF-36 v1) (Ware 
and Sherbourne, 1992, Needham et al., 2017)) and a performance-based outcome (6-
Minute Walk Test (6MWT) (Laboratories, 2002, Needham et al., 2017). 
 
Firstly, the above procedures will be carried out to ascertain the participant’s alive/deceased status 
as close to day 60 post-enrolment as possible. If no evidence of date of death is found, then the 
participant will be contacted to arrange a suitable time to carry out the rest of the outcomes. 
Patient-reported outcome measures (questionnaires) will either be carried out over the phone, by 
post, or in person (e.g. if the participant is still an in-patient at the hospital site). The performance-
based outcome will be carried out at the site and reasonable travel expenses reimbursed for 
participants as appropriate. Outcomes will be recorded as soon after day 60 as possible, with 
exact time to follow-up being recorded to inform the feasibility of doing so. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 20 of 34 
IRAS Project ID: 251112 
 
Feasibility of outcome measurement will be primarily assessed by the follow-up rate. Other 
measures of feasibility will include:  number of patients where all outcomes are completed plus 
any reasons why outcomes were not completed, for instance drop out/withdrawal rate, loss to 
follow up or death. If a participant is deceased at the time of follow-up, then they will still be 
counted as having completed the other candidate primary outcome measures. The number of 
patients who completed each individual outcome will also be measured. Measures of central 
tendency and variability of data for each outcome will inform suitability for future primary outcome 
measurement and a future sample size calculation for the RCT. Feasibility success for follow-up 
rate will be 80% minimum (Hodgson et al., 2016). After the 31st May 2019, we will not contact 
patient participants directly at day 60 follow-up, for example to confirm survival status or to carry 
out the follow-up questionnaires or walking test. However, in order to maximise participant follow 
up, we will still confirm survival status by the means set out above that do not involve direct 
contact with the participant. We will send a letter to patients that we will not follow up in person at 
day 60, to inform them of the change in study procedures. If retrospective consent has not yet 
been gained, the letter will be sent to the consultee. 
 
5.7  
END OF STUDY 
 
The end of the study will be the completion of 60-day follow up for all recruited participants, or 
when the end date of the study is reached, whichever occurs first.  
 
6. 
SAMPLE SIZE 
 
6.1 PATIENT PARTICIPANTS 
 
As outlined above, key outcomes for this study are hypothetical recruitment rate for the future RCT 
and follow-up rate of participants for day-60 outcomes.    
 
As this is an exploratory observational study with preliminary feasibility objectives, we will aim to 
recruit as many as possible to estimate these key outcomes before 31st May 2019, with a 
maximum of 40 participants. This maximum sample size number is based on local experience of 
what is feasible for recruitment to critical care studies at the host NHS Trust. A similar sample size 
justification (recruiting as many participants as possible within a pragmatic timeframe) has been 
used in a similar feasibility study for rehabilitation of patients from critical illness (Salisbury et al., 
2010), and is appropriate for the exploratory/preliminary feasibility nature of our study.  

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 21 of 34 
IRAS Project ID: 251112 
6.2 CLINICIAN PARTICIPANTS IN THE SURVEY ON ACCEPTABILITY OF 
RANDOMISATION  
 
As a maximum, we will aim to survey a nurse, doctor and physiotherapist for each patient 
participant recruited. Therefore, a maximum sample size of up to 120 clinicians will be recruited for 
this survey (three clinicians for each of the 40 patient participants). However, it is likely that the 
final number of clinicians recruited for this survey will be less than 120, for example because it 
may be appropriate to survey the same clinician for several patient participants. 
 
6.3 CLINICIAN PARTICIPANTS IN THE SURVEY ON FEASIBILITY OF THE ADVERSE 
EVENT TOOL  
 
We would like to recruit every clinician who has used the ICU physical rehabilitation adverse event 
tool as part of this research study. We are unable to accurately predict how many will use the tool 
because we are uncertain how often patient participants will be mobilised. However, a pragmatic 
estimate is that no more than 50 clinicians will use the adverse event tool. Therefore the sample 
size for this survey will be a maximum of up to 50 clinicians. If less clinicians use the tool, less 
clinicians will be recruited.  
 
 
7. 
ADVERSE EVENTS 
 
7.1 
DEFINITIONS 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect that: 
• 
Results in death 
• 
Is life-threatening – refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe 
 
• 
Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or hospitalisation 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 22 of 34 
IRAS Project ID: 251112 
but may jeopardise the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. 
 
7.2 
REPORTING PROCEDURES 
All adverse events should be reported.  Depending on the nature of the event the reporting 
procedures below should be followed.  Any questions concerning adverse event reporting should 
be directed to the Chief Investigator in the first instance. This study is observational (not involving 
changes to standard care) therefore we will only monitor for and report AEs and SAEs that are 
related to study procedures which involve contact with the participant. 
 
7.2.1 Non serious AEs 
All such events, whether expected or not, should be recorded.   
 
7.2.2 Serious AEs 
An SAE form should be completed and emailed to the Chief Investigator within 24 hours.  However, 
relapse and death due to pre-existing conditions, and hospitalisations for elective treatment of a pre-
existing condition do not need reporting as SAEs. 
 
All SAEs should be reported to the Wales Research Ethics Committee 6 where in the opinion of the 
Chief Investigator, the event was: 
• 
‘related’, ie resulted from the administration of any of the research procedures; and 
• 
‘unexpected’, ie an event that is not listed in the protocol as an expected occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  The 
Chief Investigator must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics Committee, 
Sponsor and/or Research & Development Office. 
 
Contact details for reporting SAEs 
jrco@imperial.ac.uk 
CI email (and contact details below) 
Please send SAE forms to: anthonygordon@nhs.net  
Tel: 02033126328 (Mon to Fri 09.00 – 17.00) 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 23 of 34 
IRAS Project ID: 251112 
 
 
8. 
STATISTICS AND DATA ANALYSIS 
 
For the quantitative data, descriptive statistics will be used to describe and summarise the 
outcomes set out above. For example the mean and standard deviation or median and 
interquartile range for continuous variables and numbers and percentages for categorical 
variables. All qualitative data will be analysed using qualitative content analysis (Elo and Kyngas, 
2008).  
 
Where relevant, secondary analysis may be carried out, using descriptive statistics to describe 
relevant outcomes in different patient subgroups, for example those subgroups defined in a recent 
Delphi process carried out by the authors (IRAS project ID: 212066; REC reference: 17/LO/0830). 
 
9. 
REGULATORY ISSUES  
 
9.1 
ETHICS APPROVAL 
 
The Study Coordination Centre has obtained approval from the Wales Research Ethics Committee 
(REC) 6 and Health Regulator Authority (HRA). The study will also receive confirmation of capacity 
and capability from each participating NHS Trust before accepting participants into the study or any 
research activity is carried out. The study will be conducted in accordance with the recommendations 
for physicians involved in research on human subjects adopted by the 18th World Medical Assembly, 
Helsinki 1964 and later revisions. 
 
Because this study is observational and does not change standard care, we are not aware of any 
overt risks to participants. The data collected for the study may have several implications. Firstly an 
extra burden of time on the patient/consultee when carrying out the initial survey after enrolment. In 
addition there is the burden of time in carrying out the outcome measures at day 60. This data 
collection will be carried out at a time convenient to the patient/consultee. The most amount of time 
is required for the patient coming back to the NHS site for the 6 minute walk test. This test would 
take about 45 minutes and participants will be reimbursed reasonable travel expenses for attending 
as appropriate. This test would be carried out in a hospital department where other people are close 
by and can be stopped early if required. Indeed, the purposes of this study is to test whether it is 
feasible to collect the above outcomes (i.e. is it an acceptable burden to patients) before they are 
considered in a future trial.  
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 24 of 34 
IRAS Project ID: 251112 
If answering surveys/questionnaires either at the beginning of the study or at day 60 are upsetting 
to participants, if it is felt appropriate, this will either be escalated to the ICU/hospital team (if an in-
patient) or the researcher will signpost the participant to their GP or to the Improving Access to 
Psychological Therapies service to provide support if needed. If there are concerns about the 
patients’ health at day-60 follow up, the participant’s healthcare provider would be informed. One 
potential risk of collecting additional data for research is that to confidentiality and steps to minimise 
this are outlined below. Because this study is an observational design, we are not aware of any 
additional benefits to the patient of taking part. 
 
As this study is an observational design with no changes made to current practice, no conflict of 
interest between the interests of the researcher and their duty as a health care professional are 
anticipated. If unsafe practice is identified during the research, this will be escalated to the relevant 
senior member of the clinical care team, and correct policies of the host NHS Trust followed. If 
concerns such as unsafe practice were highlighted by patient representatives, the researcher would 
signpost the patient representative to the relevant Patient Advice and Liaison Service (PALS). 
Participants will be informed that if they would like to know the study results that they can contact 
the researchers for a summary. As all data collection will be carried out at the hospital site where 
other people are present, there are no risks identified for the researchers. 
 
9.2 
CONSENT 
 
9.2.1 Identification of potential participants 
 
Potential participants will be identified through screening of routinely collected clinical data 
contained within the NHS Trust systems by members of the clinical care team. 
 
9.2.2 Approaching potential participants 
 
If inclusion criteria are met and no exclusion criteria are present, potential participants will be 
directly approached by a member of the clinical research team on the ICU.  
 
Informed consent will be sought from the patient, however because of the nature of their illnesses 
and treatments on intensive care, there is a potential for a significant proportion not to have 
capacity to consent. For example, this could be because they have reduced consciousness due to 
their critical illness or sedation required for mechanical ventilation. In these instances their 
consultee will be approached instead, then retrospective consent sought from the patient once 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 25 of 34 
IRAS Project ID: 251112 
they have capacity. This approach will be taken because this is an exploratory study trying to 
clarify standard care, it is important to gain consent early in an ICU stay so that a full picture of 
standard care can be gained. Further, our exploratory study is in preparation for a future RCT of 
ICU mobilisation. Previous trials of ICU mobilisation have tried to start the mobilisation intervention 
early in an ICU stay. Therefore, for our observational study, when assessing hypothetical 
acceptability of recruitment for patients, it is important to ask them at an equivalent time in their 
ICU stay. 
 
9.2.3 Informed consent from the patient 
 
Patients will be provided with a participant information sheet and given a full explanation of the 
study. Adequate time will be allowed for consideration and written informed consent will be sought 
if interest is expressed. Potential participants will be given as much time as they want for 
consideration, although as this study is observational and does not involve a change to clinical 
practice (and therefore is low risk) consent may be taken less than 24 hours after provision of the 
participant information sheet if participants are happy to do so. The right of the participant to 
refuse to participate without giving reasons will be respected.  All participants are free to withdraw 
at any time from the study without giving reasons and without prejudicing further treatment. 
Signed participant or consultee consent will be obtained by a member of the clinical research team 
who has completed GCP training and who has received study-specific training. This may include 
doctors, physiotherapists and research nurses.  
 
Because of the nature of ICU illness and treatment, participant’s capacity may fluctuate. If a 
participant has given informed consent, then loses capacity, we will continue to respect that 
informed consent decision and continue to include them in the study. However, if the participant 
has not regained capacity at day 60 follow up, we will not carry out the patient-reported 
questionnaires or the performance-based outcome measure, recording loss of capacity as the 
reason. Indeed, measuring that outcomes cannot be completed for this reason is important for 
answering the study objective on feasibility of outcome measurement, therefore it is important not 
to completely exclude these patients from the study as it would bias these results. 
 
We will not continue recruitment of patient participants after 31st May 2019 because it is 
anticipated that adequate recruitment will occur before this date to answer the main research 
objectives. In addition, as set out above, day 60 follow up involving direct contact with the patient 
participant will not occur after 31st May 2019. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 26 of 34 
IRAS Project ID: 251112 
 
9.2.4 Consultee advice 
If the patient lacks capacity to give informed consent, then the advice of a consultee will be sought 
on whether the patient would want to participate in the study. In the first instance, the research 
team will try to contact a personal consultee who is able to advice on the views and feelings of the 
patient. If their advice cannot be sought within a reasonable timeframe, then the advice of a 
nominated consultee (i.e. an intensive care consultant at the site – who may or may not be directly 
responsible for the patient, but not part of the study team) will be sought.  
 
The consultee will initially be approached with a consultee information sheet, the principles of 
consent will as outlined above and consultee advice will be recorded on a consultee declaration 
form. If the personal consultee is found after a nominated consultee has signed a consultee 
declaration form, then the personal consultee’s advice will be sought. If the participant is 
conscious, but does not have capacity, efforts will be made to provide verbal information to them 
about the research study. If participants appear to object to any study procedures, then their 
consultee's advice will be sought over whether to continue their participation in the study. If it is 
clear from the consultee or from the ICU case notes that there is an advanced decision or 
statement by the participants that makes it clear they would oppose taking part in the research, 
then their participation will not be sought. 
 
9.2.5 Retrospective consent from the patient 
 
If consultee advice has been gained for a participant, but then the participant regains capacity, 
then they will be informed of their current participation in the study, then retrospective consent will 
be sought from them, following the principles outlined above.  If the participant wishes to withdraw 
from the study, we will not collect further data about them. We will ask the participant’s permission 
for data already collected to be kept and used in the analysis. There may be cases where 
retrospective consent is sought at day-60 follow up. If the participant is physically present at the 
research site for follow up (for example they are returning to the site to compete the follow up 
walking test), then written consent will be sought as described above. If the participant is not 
present at the research site at follow up (for example they are unable to complete the walking test 
but wish to complete the follow up questionnaires over the phone) then verbal retrospective 
consent will be sought (and we will offer to post a copy of the retrospective participant information 
sheet).  As outlined above, after 31st May 2019, day 60 follow up involving direct contact with the 
participant will not be carried out. Therefore, for participants where day 60 occurs after this date, 
we will continue to seek retrospective consent whilst they remain an in-patient at the research site.  

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 27 of 34 
IRAS Project ID: 251112 
 
If the participant/consultee is unable to read the information sheet in English, they will not be 
recruited as there is no financial provision for translators. 
 
9.2.6 Clinician recruitment for survey on acceptability of randomisation 
When patient participants are recruited, clinicians will be asked about the hypothetical 
acceptability of patient participant’s randomisation in a future RCT and consent will be sought from 
clinicians to carry out this survey. Initial approach will be in person or via an information sheet 
emailed to potential clinical participants. This email will be sent from the clinical research team to 
the potential clinicians, i.e. sent from members of the clinical team who have routine access to 
clinician’s contact details.  
 
When a clinician is approached to take part in the survey, they will be offered the information sheet 
again, given a full explanation of the study and adequate time allowed for consideration. Then 
informed written consent will be sought if interest is expressed. The clinician will be given as much 
time as they want for consideration, although as completing the survey is low risk, consent may be 
taken less than 24 hours after provision of the participant information sheet if clinicians are happy 
to do so. The right of the clinician to refuse to participate without giving reasons will be respected.   
 
Signed consent will be obtained by a member of the clinical research team who has completed 
GCP training and who has received study-specific training as above. This consent will be for the 
duration of the study so they can then be asked about acceptability of randomisation for any future 
patient participants. All clinician participants are free to withdraw at any time from the study without 
giving reasons. 
 
9.2.7 Clinician recruitment for survey on feasibility of adverse event tool 
 
Towards the end of data collection, clinicians who have used the adverse event tool will be sent a 
brief survey about the feasibility of its use. Clinicians will be emailed the survey, which will also 
contain an information sheet about the study. Consent for taking part in this survey will be implied 
by clinicians returning it to the clinical research team.  
 
Initial approach will be in person, or via email with the survey will be sent from the clinical research 
team to the potential clinicians, i.e. from members of the clinical team who have routine access to 
clinician’s contact details. Clinicians will be given adequate time for consideration and the right of 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 28 of 34 
IRAS Project ID: 251112 
the clinician to refuse to participate without giving reasons will be respected.  All clinician 
participants are free to withdraw at any time from the study without giving reasons. 
 
9.3 
CONFIDENTIALITY 
 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act. We will maintain confidentiality of personal data in the 
following ways: 
 
9.3.1 Initial data collection 
 
• 
Identifiable data will be accessed for this research study by members of the clinical care 
team. This includes the critical care clinical research nurse team employed by the NHS Trust. 
• 
Participant recruitment into the study will be recorded in the case notes and clinicians will be 
informed so that they can complete the adverse event tool. 
• 
Data collection will initially be onto paper case report forms. Any paper study data will be 
stored in a locked cupboard, in a locked office at the NHS Trust, which is only accessible to 
the clinical research team. 
• 
Study data will also be stored on a restricted access drive on the NHS Trust computer 
system, only accessible to members of the clinical care team involved in the study.  
• 
All data collected for enrolled participants will be anonymised as soon as feasibly possible.  
• 
Patient identifiers will be linked to the rest of the study data using a unique study code for 
each participant. Identifiers and participant/next of kin contact details will be held to facilitate 
day-60 follow-up, as well as consultee details to keep them informed about the study as 
required.  
• 
The rest of the study data will not contain personal identifiers, but will contain a unique 
participant study code. 
 
9.3.2 Analysis of data 
 
• 
Only anonymised data (study data without identifiers, but containing study codes) will be 
transferred from the NHS computer system to the Imperial College London computer 
system for analysis and preparation for publication. The ‘keys’ to the study codes, which 
enable them to be linked back to individual study participants, will not leave the NHS 
computer system outlined above. This data may include direct quotes from patient 
participants and clinicians as recorded in the surveys. These anonymous direct quotes may 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 29 of 34 
IRAS Project ID: 251112 
also be published and this will be noted on participant information sheets. 
• 
Transfer will be via encrypted memory stickencrypted email, or similarly secure process. 
• 
This anonymised data will then be saved on Imperial College's OneDrive for business 
cloud storage, which is password protected, or other similarly secure electronic storage on 
the Imperial College London system.  
• 
Any of this anonymised data on paper will be stored in a locked cupboard in a locked office 
at Imperial College London, which is only accessible to the chief investigator’s research 
team. 
 
9.3.3 Long-term storage of data 
 
• 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period, as per Imperial College London 
Joint Research Compliance Office standard operating procedures. 
• 
Data held at the NHS Trust will be stored and archived for 10 years.  
• 
All anonymised research data transferred to Imperial College London will be archived at 
Imperial College London for 10 years after the end of the study  
• 
Anonymised data may be shared with other researchers to support other research projects 
in the future. 
 
9.4 
INDEMNITY 
 
Imperial College London holds negligent harm and non-negligent harm insurance policies which 
apply to this study. 
 
9.5 
SPONSOR 
 
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities will 
be assigned to the NHS trusts taking part in this study.   
 
9.6 
FUNDING 
 
This protocol details independent research arising from a Clinical Doctoral Research Fellowship, 
awarded to Huw Woodbridge, (ICA-CDRF-2015-01-026) supported by the National Institute for 
Health Research and Health Education England. The views expressed in this protocol are those of 
the author(s) and not necessarily those of the NHS, the National Institute for Health Research, 
Health Education England or the Department of Health. 
 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 30 of 34 
IRAS Project ID: 251112 
9.7 
AUDITS 
 
The study may be subject to inspection and audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research 
Governance Framework for Health and Social Care (2nd edition).  
 
10. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through Huw Woodbridge.  Research 
management will be provided by Huw Woodbridge, Prof Anthony Gordon, Prof Stephen Brett, Dr 
Caroline Alexander, and the Imperial College Joint Research Office. A steering group which includes 
a patient representative will meet regularly to discuss any issues. 
 
 
 
 
11. 
PUBLICATION POLICY 
 
It is anticipated that this proposal will produce findings that can be disseminated to open access 
peer-reviewed journals and presented at relevant conferences. Dissemination at a local level will 
occur by presentations to ICU clinicians at Imperial College Healthcare NHS Trust.  
 
12. 
REFERENCES 
 
 
AZOULAY, E., VINCENT, J. L., ANGUS, D. C., ARABI, Y. M., BROCHARD, L., BRETT, S. J., 
CITERIO, G., COOK, D. J., CURTIS, J. R., DOS SANTOS, C. C., ELY, E. W., HALL, J., 
HALPERN, S. D., HART, N., HOPKINS, R. O., IWASHYNA, T. J., JABER, S., 
LATRONICO, N., MEHTA, S., NEEDHAM, D. M., NELSON, J., PUNTILLO, K., QUINTEL, 
M., ROWAN, K., RUBENFELD, G., VAN DEN BERGHE, G., VAN DER HOEVEN, J., 
WUNSCH, H. & HERRIDGE, M. 2017. Recovery after critical illness: putting the puzzle 
together-a consensus of 29. Crit Care, 21, 296. 
BAILEY, P., THOMSEN, G. E., SPUHLER, V. J., BLAIR, R., JEWKES, J., BEZDJIAN, L., VEALE, 
K., RODRIQUEZ, L. & HOPKINS, R. O. 2007. Early activity is feasible and safe in 
respiratory failure patients. Crit Care Med, 35, 139-45. 
BIEHL, M., KASHYAP, R., AHMED, A. H., RERIANI, M. K., OFOMA, U. R., WILSON, G. A., LI, G., 
MALINCHOC, M., SLOAN, J. A. & GAJIC, O. 2015. Six-month quality-of-life and functional 
status of acute respiratory distress syndrome survivors compared to patients at risk: a 
population-based study. Crit Care, 19, 356. 
BOYD, J., PARATZ, J., TRONSTAD, O., CARUANA, L., MCCORMACK, P. & WALSH, J. 2018. 
When is it safe to exercise mechanically ventilated patients in the intensive care unit? An 
evaluation of consensus recommendations in a cardiothoracic setting. Heart Lung, 47, 81-
86. 
CHARLSON, M. E., POMPEI, P., ALES, K. L. & MACKENZIE, C. R. 1987. A new method of 
classifying prognostic comorbidity in longitudinal studies: development and validation. J 
Chronic Dis, 40, 373-83. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 31 of 34 
IRAS Project ID: 251112 
CONNOLLY, B. & DENEHY, L. 2018. Hindsight and moving the needle forwards on rehabilitation 
trial design. Thorax, 73, 203-205. 
CONNOLLY, B., O'NEILL, B., SALISBURY, L., BLACKWOOD, B. & ENHANCED RECOVERY 
AFTER CRITICAL ILLNESS PROGRAMME, G. 2016. Physical rehabilitation interventions 
for adult patients during critical illness: an overview of systematic reviews. Thorax, 71, 881-
90. 
CUTHBERTSON, B. H. & GODDARD, S. 2017. Benefits and harms of early rehabilitation. 
Intensive Care Med, 43, 1878-1880. 
DENEHY, L., NORDON-CRAFT, A., EDBROOKE, L., MALONE, D., BERNEY, S., SCHENKMAN, 
M. & MOSS, M. 2014. Outcome measures report different aspects of patient function 
three months following critical care. Intensive Care Medicine, 40, 1862-1869. 
DENEHY, L., SKINNER, E. H., EDBROOKE, L., HAINES, K., WARRILLOW, S., HAWTHORNE, 
G., GOUGH, K., HOORN, S. V., MORRIS, M. E. & BERNEY, S. 2013. Exercise 
rehabilitation for patients with critical illness: a randomized controlled trial with 12 months of 
follow-up. Critical Care, 17, 1-12. 
DOWDY, D. W., EID, M. P., DENNISON, C. R., MENDEZ-TELLEZ, P. A., HERRIDGE, M. S., 
GUALLAR, E., PRONOVOST, P. J. & NEEDHAM, D. M. 2006. Quality of life after acute 
respiratory distress syndrome: a meta-analysis. Intensive Care Med, 32, 1115-24. 
ELO, S. & KYNGAS, H. 2008. The qualitative content analysis process. J Adv Nurs, 62, 107-115. 
EUROQOL, G. 1990. EuroQol--a new facility for the measurement of health-related quality of life. 
Health Policy, 16, 199-208. 
FAN, E., DOWDY, D. W., COLANTUONI, E., MENDEZ-TELLEZ, P. A., SEVRANSKY, J. E., 
SHANHOLTZ, C., HIMMELFARB, C. R., DESAI, S. V., CIESLA, N., HERRIDGE, M. S., 
PRONOVOST, P. J. & NEEDHAM, D. M. 2014. Physical complications in acute lung injury 
survivors: a two-year longitudinal prospective study. Crit Care Med, 42, 849-59. 
FERRANTE, L. E., PISANI, M. A., MURPHY, T. E., GAHBAUER, E. A., LEO-SUMMERS, L. S. & 
GILL, T. M. 2015. Functional trajectories among older persons before and after critical 
illness. JAMA Internal Medicine, 175, 523-529. 
FERRANTE, L. E., PISANI, M. A., MURPHY, T. E., GAHBAUER, E. A., LEO-SUMMERS, L. S. & 
GILL, T. M. 2018. The Association of Frailty With Post-ICU Disability, Nursing Home 
Admission, and Mortality: A Longitudinal Study. Chest, 153, 1378-1386. 
GIRARD, T. D., ALHAZZANI, W., KRESS, J. P., OUELLETTE, D. R., SCHMIDT, G. A., TRUWIT, 
J. D., BURNS, S. M., EPSTEIN, S. K., ESTEBAN, A., FAN, E., FERRER, M., FRASER, G. 
L., GONG, M. N., HOUGH, C. L., MEHTA, S., NANCHAL, R., PATEL, S., PAWLIK, A. J., 
SCHWEICKERT, W. D., SESSLER, C. N., STRØM, T., WILSON, K. C. & MORRIS, P. E. 
2017. An Official American Thoracic Society/American College of Chest Physicians Clinical 
Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. 
Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests. American 
Journal of Respiratory and Critical Care Medicine, 195, 120-133. 
GOSSELINK, R., BOTT, J., JOHNSON, M., DEAN, E., NAVA, S., NORRENBERG, M., 
SCHONHOFER, B., STILLER, K., VAN DE LEUR, H. & VINCENT, J. L. 2008. 
Physiotherapy for adult patients with critical illness: recommendations of the European 
Respiratory Society and European Society of Intensive Care Medicine Task Force on 
Physiotherapy for Critically Ill Patients. Intensive Care Med, 34, 1188-99. 
GROLL, D. L., TO, T., BOMBARDIER, C. & WRIGHT, J. G. 2005. The development of a 
comorbidity index with physical function as the outcome. J Clin Epidemiol, 58, 595-602. 
GROUP, AVERT TRIAL COLLABORATION 2015. Efficacy and safety of very early mobilisation 
within 24 h of stroke onset (AVERT): a randomised controlled trial. The Lancet, 386, 46-55. 
HERDMAN, M., GUDEX, C., LLOYD, A., JANSSEN, M., KIND, P., PARKIN, D., BONSEL, G. & 
BADIA, X. 2011. Development and preliminary testing of the new five-level version of EQ-
5D (EQ-5D-5L). Quality of Life Research, 20, 1727-1736. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 32 of 34 
IRAS Project ID: 251112 
HERRIDGE , M. S., TANSEY , C. M., MATTÉ , A., TOMLINSON , G., DIAZ-GRANADOS , N., 
COOPER , A., GUEST , C. B., MAZER , C. D., MEHTA , S., STEWART , T. E., KUDLOW , 
P., COOK , D., SLUTSKY , A. S. & CHEUNG , A. M. 2011. Functional Disability 5 Years 
after Acute Respiratory Distress Syndrome. New England Journal of Medicine, 364, 1293-
1304. 
HICKMANN, C. E., CASTANARES-ZAPATERO, D., BIALAIS, E., DUGERNIER, J., TORDEUR, 
A., COLMANT, L., WITTEBOLE, X., TIRONE, G., ROESELER, J. & LATERRE, P.-F. 2016. 
Teamwork enables high level of early mobilization in critically ill patients. Annals of 
Intensive Care, 6, 1-11. 
HODGSON, C. L., BAILEY, M., BELLOMO, R., BERNEY, S., BUHR, H., DENEHY, L., GABBE, B., 
HARROLD, M., HIGGINS, A., IWASHYNA, T. J., PAPWORTH, R., PARKE, R., PATMAN, 
S., PRESNEILL, J., SAXENA, M., SKINNER, E., TIPPING, C., YOUNG, P., WEBB, S., 
ACTIVITY, T. T. O. E. & INVESTIGATORS, M. S. 2016. A Binational Multicenter Pilot 
Feasibility Randomized Controlled Trial of Early Goal-Directed Mobilization in the ICU*. 
Critical Care Medicine, 44, 1145-1152. 
HODGSON, C. L., UDY, A. A., BAILEY, M., BARRETT, J., BELLOMO, R., BUCKNALL, T., 
GABBE, B. J., HIGGINS, A. M., IWASHYNA, T. J., HUNT-SMITH, J., MURRAY, L. J., 
MYLES, P. S., PONSFORD, J., PILCHER, D., WALKER, C., YOUNG, M. & COOPER, D. 
J. 2017. The impact of disability in survivors of critical illness. Intensive Care Med, 43, 992-
1001. 
INVESTIGATORS, TEAM STUDY, HODGSON, C., BELLOMO, R., BERNEY, S., BAILEY, M., 
BUHR, H., DENEHY, L., HARROLD, M., HIGGINS, A., PRESNEILL, J., SAXENA, M., 
SKINNER, E., YOUNG, P. & WEBB, S. 2015. Early mobilization and recovery in 
mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort 
study. Crit Care, 19, 81. 
JANSSEN, M. F., PICKARD, A. S., GOLICKI, D., GUDEX, C., NIEWADA, M., SCALONE, L., 
SWINBURN, P. & BUSSCHBACH, J. 2013. Measurement properties of the EQ-5D-5L 
compared to the EQ-5D-3L across eight patient groups: a multi-country study. Quality of 
Life Research, 22, 1717-1727. 
KNAUS, W. A. M., DRAPER, E. A. M., WAGNER, D. P. P. & ZIMMERMAN, J. E. M. 1985. 
APACHE II: A severity of disease classification system. Critical Care Medicine, 13, 818-
829. 
LABORATORIES, A. T. S. C. O. P. S. F. C. P. F. 2002. ATS statement: guidelines for the six-
minute walk test. Am J Respir Crit Care Med, 166, 111-7. 
LONE, N. I., GILLIES, M. A., HADDOW, C., DOBBIE, R., ROWAN, K. M., WILD, S. H., MURRAY, 
G. D. & WALSH, T. S. 2016. Five-Year Mortality and Hospital Costs Associated with 
Surviving Intensive Care. American Journal of Respiratory and Critical Care Medicine, 194, 
198-208. 
MCDOWELL, K., O'NEILL, B., BLACKWOOD, B., CLARKE, C., GARDNER, E., JOHNSTON, P., 
KELLY, M., MCCAFFREY, J., MULLAN, B., MURPHY, S., TRINDER, T. J., LAVERY, G., 
MCAULEY, D. F. & BRADLEY, J. M. 2017. Effectiveness of an exercise programme on 
physical function in patients discharged from hospital following critical illness: a randomised 
controlled trial (the REVIVE trial). Thorax, 72, 594-595. 
MORRIS, P. E., BERRY, M. J., FILES, D. C., THOMPSON, J. C., HAUSER, J., FLORES, L., 
DHAR, S., CHMELO, E., LOVATO, J., CASE, L. D., BAKHRU, R. N., SARWAL, A., 
PARRY, S. M., CAMPBELL, P., MOTE, A., WINKELMAN, C., HITE, R. D., NICKLAS, B., 
CHATTERJEE, A. & YOUNG, M. P. 2016. Standardized Rehabilitation and Hospital Length 
of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial. 
JAMA, 315, 2694-702. 
MOSS, M., NORDON-CRAFT, A., MALONE, D., VAN PELT, D., FRANKEL, S. K., WARNER, M. 
L., KRIEKELS, W., MCNULTY, M., FAIRCLOUGH, D. L. & SCHENKMAN, M. 2015. A 
Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 33 of 34 
IRAS Project ID: 251112 
Respiratory Failure. American Journal of Respiratory and Critical Care Medicine, 193, 
1101-1110. 
MUSCEDERE, J., WATERS, B., VARAMBALLY, A., BAGSHAW, S. M., BOYD, J. G., MASLOVE, 
D., SIBLEY, S. & ROCKWOOD, K. 2017. The impact of frailty on intensive care unit 
outcomes: a systematic review and meta-analysis. Intensive Care Medicine, 43, 1105-
1122. 
NEEDHAM, D. M., SEPULVEDA, K. A., DINGLAS, V. D., CHESSARE, C. M., FRIEDMAN, L. A., 
BINGHAM, C. O., 3RD & TURNBULL, A. E. 2017. Core Outcome Measures for Clinical 
Research in Acute Respiratory Failure Survivors. An International Modified Delphi 
Consensus Study. Am J Respir Crit Care Med, 196, 1122-1130. 
NICE 2009. Rehabilitation after critical illness. National Institute for Health and Clinical 
Excellence. 
NICKELS, M. R., AITKEN, L. M., WALSHAM, J., BARNETT, A. G. & MCPHAIL, S. M. 2017. 
Critical Care Cycling Study (CYCLIST) trial protocol: a randomised controlled trial of usual 
care plus additional in-bed cycling sessions versus usual care in the critically ill. BMJ Open, 
7, e017393. 
NIEVERA, R. A., FICK, A. & HARRIS, H. K. 2016. Effects of Ambulation and Nondependent 
Transfers on Vital Signs in Patients Receiving Norepinephrine. Am J Crit Care, 26, 31-36. 
NYDAHL, P., SRICHAROENCHAI, T., CHANDRA, S., KUNDT, F. S., HUANG, M., FISCHILL, M. 
& NEEDHAM, D. M. 2017. Safety of Patient Mobilization and Rehabilitation in the Intensive 
Care Unit. Systematic Review with Meta-Analysis. Ann Am Thorac Soc, 14, 766-777. 
PARRY, S. M., NYDAHL, P. & NEEDHAM, D. M. 2018. Implementing early physical rehabilitation 
and mobilisation in the ICU: institutional, clinician, and patient considerations. Intensive 
Care Med, 44, 470-473. 
PUGH, R. J., ELLISON, A., PYE, K., SUBBE, C. P., THORPE, C. M., LONE, N. I. & CLEGG, A. 
2018. Feasibility and reliability of frailty assessment in the critically ill: a systematic review. 
Crit Care, 22, 49. 
PUTHUCHEARY, Z. A. & DENEHY, L. 2015. Exercise Interventions in Critical Illness Survivors: 
Understanding Inclusion and Stratification Criteria. Am J Respir Crit Care Med, 191, 1464-
7. 
PUTHUCHEARY, Z. A., RAWAL, J., MCPHAIL, M., CONNOLLY, B., RATNAYAKE, G., CHAN, P., 
HOPKINSON, N. S., PHADKE, R., DEW, T., SIDHU, P. S., VELLOSO, C., SEYMOUR, J., 
AGLEY, C. C., SELBY, A., LIMB, M., EDWARDS, L. M., SMITH, K., ROWLERSON, A., 
RENNIE, M. J., MOXHAM, J., HARRIDGE, S. D., HART, N. & MONTGOMERY, H. E. 
2013. Acute skeletal muscle wasting in critical illness. JAMA, 310, 1591-600. 
REBEL, A., MARZANO, V., GREEN, M., JOHNSTON, K., WANG, J., NEEMAN, T., MITCHELL, I. 
& BISSETT, B. 2018. Mobilisation is feasible in intensive care patients receiving vasoactive 
therapy: An observational study. Aust Crit Care. 
ROCKWOOD, K., SONG, X., MACKNIGHT, C., BERGMAN, H., HOGAN, D. B., MCDOWELL, I. & 
MITNITSKI, A. 2005. A global clinical measure of fitness and frailty in elderly people. 
CMAJ, 173, 489-95. 
SALISBURY, L., MERRIWEATHER, J. & WALSH, T. 2010. The development and feasibility of a 
ward-based physiotherapy and nutritional rehabilitation package for people experiencing 
critical illness. Clinical Rehabilitation, 24, 489-500. 
SCHALLER, S. J., ANSTEY, M., BLOBNER, M., EDRICH, T., GRABITZ, S. D., GRADWOHL-
MATIS, I., HEIM, M., HOULE, T., KURTH, T., LATRONICO, N., LEE, J., MEYER, M. J., 
PEPONIS, T., TALMOR, D., VELMAHOS, G. C., WAAK, K., WALZ, J. M., ZAFONTE, R. & 
EIKERMANN, M. 2016. Early, goal-directed mobilisation in the surgical intensive care unit: 
a randomised controlled trial. The Lancet, 388, 1377-1388. 
SCHWEICKERT, W. D., POHLMAN, M. C., POHLMAN, A. S., NIGOS, C., PAWLIK, A. J., 
ESBROOK, C. L., SPEARS, L., MILLER, M., FRANCZYK, M., DEPRIZIO, D., SCHMIDT, 
G. A., BOWMAN, A., BARR, R., MCCALLISTER, K. E., HALL, J. B. & KRESS, J. P. 2009. 

Joint Research  
Compliance Office 
 
Exploration of investigating ICU mobilisation with vasoactive drugs v1 
Observational Protocol, V3, 200519 
    
Page 34 of 34 
IRAS Project ID: 251112 
Early physical and occupational therapy in mechanically ventilated, critically ill patients: a 
randomised controlled trial. Lancet, 373, 1874-82. 
SRICHAROENCHAI, T., PARKER, A. M., ZANNI, J. M., NELLIOT, A., DINGLAS, V. D. & 
NEEDHAM, D. M. 2014. Safety of physical therapy interventions in critically ill patients: a 
single-center prospective evaluation of 1110 intensive care unit admissions. J Crit Care, 
29, 395-400. 
STILLER, K., PHILLIPS, A. & LAMBERT, P. 2004. The safety of mobilisation and its effect on 
haemodynamic and respiratory status of intensive care patients. Physiotherapy Theory and 
Practice, 20, 175-185. 
TIPPING, C. J., HARROLD, M., HOLLAND, A., ROMERO, L., NISBET, T. & HODGSON, C. L. 
2017. The effects of active mobilisation and rehabilitation in ICU on mortality and function: 
a systematic review. Intensive Care Med, 43, 171-183. 
USTUN, T. B., CHATTERJI, S., KOSTANJSEK, N., REHM, J., KENNEDY, C., EPPING-JORDAN, 
J., SAXENA, S., VON KORFF, M., PULL, C. & PROJECT, W. N. J. 2010. Developing the 
World Health Organization Disability Assessment Schedule 2.0. Bull World Health Organ, 
88, 815-23. 
VINCENT, J. L., DE MENDONCA, A., CANTRAINE, F., MORENO, R., TAKALA, J., SUTER, P. M., 
SPRUNG, C. L., COLARDYN, F. & BLECHER, S. 1998. Use of the SOFA score to assess 
the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, 
prospective study. Critical Care Medicine, 26, 1793-1800. 
WARE, J. E., JR. & SHERBOURNE, C. D. 1992. The MOS 36-item short-form health survey (SF-
36). I. Conceptual framework and item selection. Med Care, 30, 473-83. 
WARE, J. E. J. 2000. SF-36 Health Survey Update. Spine, 25, 3130-3139. 
WRIGHT, S. E., THOMAS, K., WATSON, G., BAKER, C., BRYANT, A., CHADWICK, T. J., SHEN, 
J., WOOD, R., WILKINSON, J., MANSFIELD, L., STAFFORD, V., WADE, C., FURNEVAL, 
J., HENDERSON, A., HUGILL, K., HOWARD, P., ROY, A., BONNER, S. & BAUDOUIN, S. 
2018. Intensive versus standard physical rehabilitation therapy in the critically ill (EPICC): a 
multicentre, parallel-group, randomised controlled trial. Thorax, 73, 213-221.