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Trial registered on ANZCTR


Registration number
ACTRN12619000637145p
Ethics application status
Not yet submitted
Date submitted
23/04/2019
Date registered
30/04/2019
Date last updated
30/04/2019
Date data sharing statement initially provided
30/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Chronic Pain in Survivors of Intensive Care
Scientific title
Pain After Survival From the Intensive Care Unit (PAIN-ICU): A Prospective, Multicentre, Observational Cohort Study to Determine the Incidence, Risk Factors and Impact of Chronic Pain in Critically Ill Adult Patients Discharged from ICU.
Secondary ID [1] 296811 0
None
Universal Trial Number (UTN)
U1111-1225-0700
Trial acronym
PAIN-ICU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Pain 312504 0
Critical Illness 312505 0
Post-Traumatic Stress Disorder 312506 0
Condition category
Condition code
Mental Health 311049 311049 0 0
Other mental health disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The outcome of chronic pain will be determined by a 30-minute phone interview 6 months after ICU discharge. A questionnaire will determine the incidence and characteristics of Chronic Post-ICU Pain (CPIP) and the impact of chronic pain (post-traumatic stress disorder, prolonged opioid use, anxiety, depression, productivity). Data collected during the ICU admission will determine modifiable risk factors for the development of chronic pain.
Intervention code [1] 314270 0
Not applicable
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319838 0
Chronic Pain assessed by the question "Over the past 6 months, have you had pain on at least half the days?"
Timepoint [1] 319838 0
6 Months post-ICU discharge
Secondary outcome [1] 369648 0
Risk Factors for developing chronic pain.
Risk factors will be assessed using logistic regression for the dichotomous outcome of chronic pain (yes/no).

Pre-specified potential risk factors acquired from medical notes and include:
Age
Gender
APACHE2 score (calculated after 24 hours in ICU)
Presence of Sepsis (from the Sepsis 3 definition)- data collected in APACHE2
Admission diagnosis
% Time outside target pain scores (average time where the patient is above pain score target)
Type of Opioid
Cumulative Opioid Dose (measured in oral morphine equivalent daily doses, o-MEDD)
Simple analgesia used (paracetamol, NSAIDS)
Ketamine infusion
Regional analgesia
Type of Sedation used
Immobilisation scale (using the ICU Mobility Scale)


Timepoint [1] 369648 0
ICU admission data collected at timepoint 0.
Secondary outcome [2] 369649 0
Incidence of prolonged opioid use assessed by questionnaire (Brief Pain Inventory) at 6 months post-ICU discharge.
Timepoint [2] 369649 0
6 months post-ICU discharge
Secondary outcome [3] 369650 0
Incidence of post-traumatic stress disorder assessed by questionnaire (Impact of Events Screening- Revised) at 6 months post-ICU discharge.
Timepoint [3] 369650 0
6 months post-ICU discharge
Secondary outcome [4] 369651 0
Incidence of anxiety assessed by questionnaire (Hospital Anxiety and Depression Scale) at 6-months post-ICU discharge.
Timepoint [4] 369651 0
6 months post-ICU discharge
Secondary outcome [5] 369652 0
Incidence of depression assessed by questionnaire (Hospital Anxiety and Depression Scale) at 6-months post-ICU discharge.
Timepoint [5] 369652 0
6 months post-ICU discharge
Secondary outcome [6] 369653 0
Productivity assessed by questionnaire (Work Productivity and Activity Impairment Questionnaire: Specific Health Problem) at 6-months post-ICU discharge.
Timepoint [6] 369653 0
6 months post-ICU discharge
Secondary outcome [7] 369776 0
Quality of Life assessed by questionnaire (EQ-5D-5L) at 6-months post-ICU discharge.
Timepoint [7] 369776 0
6-months post-ICU discharge.

Eligibility
Key inclusion criteria
1. Patients admitted to the intensive care unit that have survived to ICU discharge.
2. Age > 18 years.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known diagnosis of chronic pain.
2. Death is deemed inevitable or imminent during this admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment.
3. Known diagnosis of mild to severe cognitive impairment.
4. Proven or suspected primary neurological lesion including traumatic brain injury (TBI), subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH), cerebrovascular accident (CVA), hypoxic ischaemic encephalopathy (HIE).
5. Inability to communicate in English.
6. The patient has been previously enrolled in the trial.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Logistic regression will be used to a build a predictive model for the dichotomous outcome chronic pain at 6 months post discharge. Parameters will be estimated using LASSO (least absolute shrinkage and selection operator) in order to avoid over-fitting. Receiver Operating Characteristic (ROC) curves will be constructed from this model and the area under the curve will be reported as a measure of predictive ability. Calibration will be assessed using calibration plots and the Hosmer-Lemeshow test. Logistic regression models will be used to explore potentially causal effects of modifiable clinical variables with chronic pain, with Directed Acyclic graphs constructed to determine the confounding variable(s) that needs to be accounted for in the model. Linear regression models will be used to assess continuous secondary outcome variables.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 13649 0
Gosford Hospital - Gosford
Recruitment hospital [2] 13650 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 26326 0
2250 - Gosford
Recruitment postcode(s) [2] 26327 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 301384 0
Hospital
Name [1] 301384 0
Gosford Hospital Caring for the Future Grant
Address [1] 301384 0
Gosford Hospital, Holden St, Gosford, NSW, 2251
Country [1] 301384 0
Australia
Funding source category [2] 302569 0
Hospital
Name [2] 302569 0
John Hunter Hospital Charitable Trust Research Grant
Address [2] 302569 0
John Hunter Hospital, Lookout Rd, New Lambton, NSW, 2305
Country [2] 302569 0
Australia
Funding source category [3] 302570 0
Other Collaborative groups
Name [3] 302570 0
Hunter Medical Research Institute Clinical Research Design, IT and Statistical Support (CReDDITT) Funding
Address [3] 302570 0
Lot 1, Kookaburra Cct, New Lambton Heights, NSW, 2305
Country [3] 302570 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Critical Care and Trauma Division
Level 5, 1 King St, Newtown, NSW, 2042
Country
Australia
Secondary sponsor category [1] 302478 0
None
Name [1] 302478 0
Address [1] 302478 0
Country [1] 302478 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 302122 0
HNEHREC
Ethics committee address [1] 302122 0
John Hunter Hospital, Lookout Rd, New Lambton, NSW 2305
Ethics committee country [1] 302122 0
Australia
Date submitted for ethics approval [1] 302122 0
01/05/2019
Approval date [1] 302122 0
Ethics approval number [1] 302122 0

Summary
Brief summary
Improvements in the management of critically ill patients have resulted in improved survival. However, these survivors are at an increased risk of cognitive, psychiatric and physical disability. This constellation of symptoms is known as Post-ICU Syndrome (PICS). One particular component of PICS is the development of chronic pain. Clinically and epidemiologically, chronic pain has been defined as pain that persists for 3 months or more

Currently, the incidence of chronic pain in survivors of intensive care in Australia is unknown. The current literature from overseas estimates the incidence of chronic pain to be between 40-60% of ICU survivors. To date, there are no studies that have identified modifiable risk factors that therapeutic interventions can target to prevent the development of chronic pain. In addition, there is no literature about long-term opioid use in survivors of ICU.

Hence, noting that there is a high incidence of chronic pain in ICU survivors, we aim to confirm this and hypothesise that risk factors associated with analgesic management, sedative management and immobility are implicated in the development of chronic pain.

We plan to do this by conducting a large cohort study that accurately measures chronic pain using internationally recommended definitions. In addition, we will evaluate the impact of chronic pain (i.e. requirement of opioids, quality of life, interference, neuropathic components, psychiatric comorbidities, employment) using validated scales. We will also identify modifiable risk factors to develop targeted therapeutic interventions that aim to reduce the incidence of chronic pain, which will inform larger therapeutic clinical trials.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89190 0
Dr Benjamin Moran
Address 89190 0
Critical Care and Trauma Division,
The George Institute for Global Health,
Level 5, 1 King St, Newtown, NSW, 2042
Country 89190 0
Australia
Phone 89190 0
+61 2 8052 4300
Fax 89190 0
Email 89190 0
bmoran@georgeinstitute.org.au
Contact person for public queries
Name 89191 0
Dr Benjamin Moran
Address 89191 0
Critical Care and Trauma Division,
The George Institute for Global Health,
Level 5, 1 King St, Newtown, NSW, 2042
Country 89191 0
Australia
Phone 89191 0
+61 2 8052 4300
Fax 89191 0
Email 89191 0
bmoran@georgeinstitute.org.au
Contact person for scientific queries
Name 89192 0
Dr Benjamin Moran
Address 89192 0
Critical Care and Trauma Division,
The George Institute for Global Health,
Level 5, 1 King St, Newtown, NSW, 2042
Country 89192 0
Australia
Phone 89192 0
+61 2 8052 4300
Fax 89192 0
Email 89192 0
bmoran@georgeinstitute.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results