Design
The trial, termed EFFORT-ICU, is a Phase II feasibility trial incorporating a mixed methods design. The study follows the guidelines for feasibility trials outlined by the SPIRIT 2013 Statement [19]. EFFORT-ICU is a prospective single-centre, single blinded, equally randomised controlled trial (1:1) comparing standard occupational therapy care to an early functional occupation-based retraining therapy program. A study overview is shown in Figure 1.
Ethics / Governance
Ethical approval for the study from the Metro South Hospital and Health Service Human Research Ethics Committee (EC00167) and The University of Queensland was gained on 27th April 2018 for a 3-year recruitment study cycle. The trial may be independently audited by the ethics committees at any time. Any modifications to the protocol (e.g., changes to eligibility criteria, outcomes) will be approved by the ethics committees and communicated to all investigators and the trial registry.
Participants
The study will be conducted in a level two adult eight bed intensive care unit at Logan Hospital, Brisbane, Australia. All patients admitted to the intensive care unit will be included if they are aged over 18 years and are expected to require invasive mechanical ventilation for greater than 48 hours.
Patients will be excluded from the trial if:
- They are admitted to the intensive care unit but do not require mechanical ventilation
- They have been readmitted to the intensive care unit from the current hospitalisation
- A withdrawal of treatment is expected to occur within the next 24 hours or they are not expected to survive the current intensive care unit admission
- They have a poor level of functional ability prior to admission (requiring carer assistance / high dependency level in activities of daily living as measured by a Modified Barthel Index score <40)
- They have a pre-existing severe cognitive deficit (as identified by completion of the short form IQCODE with an average score above 3.31-3.38)
- They have a pre-existing significant mental health disorder impacting on participation
- They live interstate and would be unable to attend the 90 days post-randomisation follow-up in person
- They are unable to communicate in English.
Patients admitted over the weekend where occupational therapy intervention cannot be immediately initiated will be eligible to participate in the trial, and therapy will begin on the first working day.
Recruitment
A consecutive sampling model will be used where all patients who meet the eligibility criteria will be invited to participate. All patients admitted to the intensive care unit will be screened for eligibility on a daily basis by clinical staff. Patients meeting the study criteria will be referred to the research team within 24 hours of admission. Written informed consent will be sought.
Consent
Participants will be invited to provide consent at the time of recruitment if able to do so. If due to medical conditions, the participant is unable to provide informed consent, the person responsible will be approached to provide consent on their behalf. In addition, informed consent will be sought from the person responsible to act as a significant other participant during the qualitative interviews in Part 2. Once a participant is able to provide their own consent, they will be given an opportunity to continue with the trial or withdraw. Eligible participants will be informed that participation in the study is voluntary and if they choose not to participate, or if they choose to withdraw from the study after consenting, this will in no way affect their normal treatment at the hospital.
The study will be explained verbally by the chief investigator or nominated delegate. The participant or person responsible will be given the opportunity to read the information sheet and ask any questions prior to participation in the study. The participant or person responsible will be provided with a copy of the signed consent form and the information sheet and any other documentation discussed throughout the consent process.
Randomisation and blinding
Following consent, participants will be randomly allocated to either the intervention group who will receive early occupation-based activity or the control group who will receive standard occupational therapy, medical, nursing and physiotherapy care. Patients will be randomised into the intervention and control groups via computer generated numbers (http://www.randomization.com/) which will be sealed in consecutively numbered opaque envelopes. The production of the envelopes will be performed by research support staff who will not be involved in the interventions.
Blinding
It will not be possible to blind the research team or the participants to group assignment. However participant outcome measurement assessors will be blinded to participant assignment. The blind assessors will be other occupational therapists who work at the hospital but not in the intensive care unit, or with patients who have been transferred from intensive care.
Interventions
Control Group: The control group will receive usual occupational therapy care. At Logan Hospital an occupational therapist attends daily clinical ward rounds within the intensive care unit. Patients are identified based on clinical needs and daily prioritisation guidelines for operation within an acute hospital. Core non-functional risk remediation activities such as splinting (for example to prevent foot drop) and pressure cushion provision are provided on an immediate basis when clinical need is identified. Functional therapy is completed at the discretion of therapists and clinical caseload weighting and may be absent in most units.
Intervention Group: Early occupation-based purposeful activity interventions will be administered based on a graded plan (according to the Richmond Agitation and Sedation Scale (RASS)[20] and medical stability). A manualised intervention strategy will be followed to ensure consistency of approaches. A precautions checklist will be completed prior to each therapy session to ensure medical stability and clearance for activity participation. The checklist was created based on expert consensus guidelines for mobilisation in the intensive care unit and adapted to functional and cognitive participation requirements [21] . See Table 1 for contraindications to treatment.
Table 1: Checklist for Contraindications to Intervention
|
- O2 Saturation < 90 %
- Respiratory Rate > 30bpm
- Fi O2 > 0.6
- PEEP > 10cm H2O / ventilator dysynchrony
- Any rescue therapies (NO, Prostatcyclin, prone)
- Significant antihypertensive medications
- MAP (below target, various support measures)
- Bradycardia on significant pharmacological support
- Tachycardia >150bpm
- RASS > 2+
- Large open wound / uncontrolled active bleeding
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The aim of the trial is to implement an early occupational-based and cognitive stimulation intervention, focusing on the amount, structure and quality of occupation-based therapy. Interventions will be graded according to functional ability. Patients in the intervention group will receive a minimum total of 60 minutes daily engagement in self-care or grooming tasks adapted to the patient’s current functional ability. Functional tasks will include hand-over-hand facilitation of grooming tasks, self-care activities in the bed, bedside or bathroom, and leisure related activities. A cognitive component, such as semantic memory tagging (linking learnt facts with new memories), will be incorporated within the functional task. Intervention activity options will be based on an interview about leisure preferences and premorbid lifestyle with the person responsible, to enable appropriate activity choices for optimised participation.
Cognitive stimulation tasks incorporated within the functional tasks will be modified according to the patient’s level of cognitive function. Cognitive tasks incorporated within functional activities will include sensory stimulation and sensory modulation, daily orientation, engagement and reflection on task performance (using judgement and insight), attention challenges through task set-up, active daily planning and goal setting, and iPad tasks impacting on or enhancing functional participation.
All occupational therapists expected to work within the intensive care unit will be trained and become familiar with the intervention manual prior to the study. All interventions will be delivered by the two trained specialist critical care occupational therapists based on the intervention manual. Training will be provided by the principal investigator (ARB) over a 3 month period incorporating observation and clinical reflection examples. Two reserve therapists whose primary caseload is not in the intensive care unit will be trained by ARB to ensure all functional sessions can be completed even in absence of usual critical care staff (for example due to annual leave or unexpected absence).
Qualitative Follow-Up
Part 2 of this study includes a qualitative component and will be guided by interpretive description [22] to explore the lived experience of participants receiving the intervention and the perception of family members or the most involved significant other. At 90 days post randomisation, all patients from the occupation-based therapy intervention group will be invited to participate in in-depth semi-structured interviews targeted towards exploring their experience of engaging within the early occupation-based purposeful activity program. In the event that the participant is too unwell to physically attend an interview, alternative arrangements, such as telephonic interview, will be offered.
The person responsible will be provided with a separate information and consent form to participate in the interview.
Interviews will be conducted by the principal researcher in a private, wheelchair accessible room at Logan Hospital. Funding for transport will be provided to facilitate attendance at interviews. Wheelchair accessible transport will be organised for participants who require specialist accessibility options. Interviews will be audiotaped and transcribed verbatim by a transcription service.
Data Collection
Data on recruitment, including number of eligible and consenting patients and reasons for non-consent, will be collected. Patient demographic data including age, gender, ICU admission diagnosis, co-morbid diseases, date of admission to ICU, ICU length of stay, hospital length of stay, hospital discharge destination and support level required on discharge from hospital will be collected from the medical records. Severity of illness will be measured using the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system [23].
Duration of mechanical ventilation will be extracted from the Australia New Zealand Intensive Care Society ANZICS Adult Patient Database (APD). The time schedule for enrollments and administration of assessments and outcome measures is illustrated in Table 2. Retention data including number of withdrawals and reason for withdrawal will be collected.
Outcome measures
Primary Outcome Measure:
Independence within activities of daily living will be measured using the Functional Independence Measure (FIM™). The FIM will quantify the participant’s functional and cognitive status at intensive care unit and hospital discharge, as well as at 90 days post-randomisation. This tool is validated for use in the critically ill population [24, 25] and provides reliable information regarding patient functional change during rehabilitation across various hospital and community settings [26]. The FIM will be conducted within 24 hours of the expected discharge from the intensive care unit and hospital or on the Friday before the expected discharge, if likely to occur over the weekend. It will also be administered during the 90 days follow up session. The FIM will be performed by an occupational therapist blinded to participant assignment groups and who does not actively work on the Intensive Care Unit.
Secondary Outcome Measures:
- The Modified Barthel Index (MBI) [27] is used to measure functional ability and serves as a secondary measure included for its ability to detect change within self-care and functional tasks. The MBI is commonly used in hospital settings, although recent research has highlighted ceiling effects and lack of reliability [28]. The MBI also provides an additional source of comparison across multiple earlier critical care rehabilitation studies. The MBI will be used at multiple time points including allocation to intervention, intensive care unit discharge, hospital discharge and 90 days post randomisation follow up.
- The Montreal Cognitive Assessment (MoCA) [29] is a screening measure of cognition and assesses multiple domains of cognition including attention, memory and visuospatial relations. It is commonly used within the acute and community setting and demonstrates high criterion and convergent validity within the acute care setting [30]. The MoCA will be administered at discharge from intensive care unit, hospital and 90 days post-randomisation follow up using alternate versions at each time point [31].
- Grip strength will be measured using a dynamometer (Jamar) [32] at discharge from intensive care unit and hospital, and 90 days post randomisation follow up. Grip strength is used as a measure of Intensive Care Unit Acquired Weakness (ICUAW) and infers a relation between weakness and inability to complete functional activities independently [33].
- The Short-Form (36) Health Survey (SF-36v2™) will provide a baseline and post discharge measure of participants’ health related quality of life (HRQOL). The SF-36v2™ is a validated and reliable tool [34] and has been further validated within the critical care setting [35]. This will be completed at intensive care unit discharge, and 90 days post randomisation follow up.
- Sedation and delirium status will be measured using the validated Richmond Agitation Sedation Scale (RASS) [20] and the reliable and validated Confusion Assessment Method for ICU (CAM-ICU) [36]. These scores are regularly administered by nursing staff throughout a 24 hour period. RASS and CAM-ICU scores immediately prior to and following early occupation-based interventions will be collected for additional analysis. RASS and CAM-ICU scores for the control group participants will be collected daily at 9am.
- The Glasgow Coma Scale (GCS) [37] is used to evaluate the level of consciousness in patients with neurological conditions or severe injury [38] and will be collected daily at 9am in the control group, and pre-treatment in the intervention group.
- Hospital Anxiety and Depression Scale (HADS) [39] is a measure of emotional distress regarding anxiety and depression. It has been validated with the use of critical care survivors [40]. It will be administered at discharge from intensive care unit, hospital and 90 days post randomisation follow up.
- The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) (short form) [41] is a reliable and validated measure used to screen for cognitive dysfunction. It will be used as a screening tool for eligibility to the trial and will be completed by the participant’s person responsible.
- The Short Portable Mental Status Questionnaire (MSQ) [42] is a brief orientation checklist used to demonstrate current and previous memory linked to orientation. It is a 10 statement questionnaire that is easily administered at the bedside. It will be completed pre-and post-treatment in the intervention group, and at 9am in the control group.
Table 2: Time schedule of enrolment and assessments for participants
Measure
|
Enrolment
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Allocation to Intervention
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ICU Stay
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ICU Discharge
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Hospital Discharge
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Follow up 90 days
|
Eligibility Screen
|
x
|
|
|
|
|
|
Informed Consent
|
x
|
|
|
|
|
|
Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)
|
x
|
|
|
|
|
|
Demographic
|
|
x
|
|
|
|
|
APACHE II
|
|
x
|
|
|
|
|
Modified Barthel Index (MBI)
|
x
(Reported)
|
|
|
x
|
x
|
x
|
Grip Strength (Dynamometer)
|
|
|
|
x
|
x
|
x
|
Functional Independence Measure (FIM)
|
|
|
|
x
|
x
|
x
|
Short Form (SF-36v2)
|
|
|
|
x
|
|
x
|
Hospital Anxiety and Depression Scale (HADS)
|
|
|
|
x
|
x
|
x
|
Confusion Assessment Measure (CAM-ICU)
|
|
|
Daily
|
|
|
|
Glasgow Coma Scale (GCS)
|
|
|
Daily
|
|
|
|
Short Portable Mental Status Questionnaire (MSQ)
|
|
|
Daily
|
|
|
|
Richmond Agitation and Sedation Scale (RASS)
|
|
|
Daily
|
|
|
|
Montreal Cognitive Assessment (MoCA)
|
|
|
|
x
|
x
|
x
|
Dose of Occupational Therapy
|
|
|
Daily
|
|
|
|
Intervention fidelity checking through notes audit
|
|
|
Daily
|
|
|
|
Data management
All data for the individual participants will be collected by the chief investigator and co-investigator therapists who will administer the interventions. Participants will be allocated a participant number for the trial. All case report form (CRF) data will be entered into a password protected data sheet for analysis and storage.
Sample Size
A sample size of 30 participants has been chosen, based on recommendations regarding pilot and feasibility trials evaluating outcomes [43]. Fifteen patients from the intervention group will be included within the qualitative component carried out at 90 days post-randomisation.
Statistical analysis
All data from the case report form (CRF) will be entered into a purposefully designed Excel database and exported into SPSS version 22.0 for analyses. Descriptive statistics will be used to determine the distributions of the data for the intervention and control groups and to test whether statistical assumptions for parametric tests are achieved. Imputation will be used to correct for missing data. Groups will be compared to identify baseline differences on measures. Analyses will be performed on an intention-to-treat and per protocol method. Continuous variables that are normally distributed will be compared between the groups at each follow-up using an independent groups t-test. Effect sizes will be calculated using Cohen’s d. Non-parametric analysis will be conducted for continuous variables that are not normally distributed. Categorical variables will be compared with the chi-square statistic. A p value of 0.05 will be considered statistically significant. Where appropriate, analyses will be reported with mean differences and 95% CI. Protocol violations regarding the intervention manual strategies will be noted. Analysis of the screening log will provide information regarding potential eligible participants that may influence phase III trial recruitment. The effect size for the primary outcome variable will be used to determine the required sample size for a fully powered trial.
Semi-structured qualitative interview data will be transcribed and analysed using thematic analysis to identify key perceptions, self-reported experience and highlight factors that may contribute to future clinical care design. Two members of the research team will independently code a portion of the data.
Analysis of Session Content
All case notes of patients seen by occupational therapy will be audited and analysed to categorise common therapeutic interventions used, and determine fidelity with respect to adherence to manualised intervention protocol. Deviations from the protocol will be reviewed. Case notes for patients experiencing usual care will also be analysed to identify if any cross-over of groups occurred. Number of interventions delivered will recorded for each intervention participant, detailing reasons for missed therapy sessions.
Adverse event management
There is no anticipated harm associated with participating in the early rehabilitation program. All occupational therapists carrying out the interventions will be trained and experienced critical care staff. Unforeseeable changes in medical condition may influence the type and content of therapy sessions and there may be a period where therapy is reduced under the guidance of the medical team until organ system stabilisation has occurred. Therapy will be initiated as soon as both medical and allied health teams identify that safe mobilisation practices can be re-implemented. The nature of medical complications impacting on delivery of the intervention will be documented.
Occupational therapy staff completing the outcome measures are familiar with the complex caseload of patients and will be sensitive to the vulnerable nature of the questions and outcome measures used. Staff will invite participants to have a family member / support person present, and will cease the assessment if a participant becomes distressed. Emotional and physical safety of the vulnerable participants will be their primary concern.
The qualitative interviews will be carried out by an experienced critical care occupational therapist who is familiar with the sensitive and vulnerable nature of the participants. It is acknowledged that asking participants to recall their time in intensive care has the potential to be distressing. Questioning will cease if the participant becomes distressed, and a family member/ support person will be invited to attend should they not already be present. Participants will be provided with further information regarding community support services or organisations should they need ongoing support with coping.
Confidentiality and Security
All patient data (paper copy and secure computer files) pertaining to the study will be stored maintaining confidentiality in accordance with local legislation on privacy and the use of health data.
Confidentiality of all patient information will be safeguarded through coding mechanisms and stored in secure locked conditions with access limited to study personnel. Electronic files will be password protected. The chief investigator will maintain the confidentiality of all study documentation and participants, and take measures to prevent accidental or premature destruction of these documents, and prevent access to this data by any unauthorised third party. Information will be de-identified. Each participant will be given a unique identifier linked to a master list. The master list will be stored separately to the data and will only be accessed by the chief investigator.
The investigator will retain study documents for at least 15 years after the completion of the study. Study documents will be disposed of securely after 15 years – paper documents will be shredded, and computerized data will be permanently erased and back-ups physically destroyed.