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Trial registered on ANZCTR


Registration number
ACTRN12622000625774
Ethics application status
Approved
Date submitted
8/04/2022
Date registered
28/04/2022
Date last updated
25/11/2022
Date data sharing statement initially provided
28/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Analgesia for major abdominal surgery: A feasibility study using a combination of intrathecal and epidural morphine
Scientific title
Analgesia for major abdominal surgery: A feasibility study using a combination of intrathecal and epidural morphine
Secondary ID [1] 306878 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postoperative pain
 325979 0
Quality of recovery 325980 0
Condition category
Condition code
Anaesthesiology 323293 323293 0 0
Pain management
Anaesthesiology 323294 323294 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Epidural Morphine Group
o Combined spinal epidural prior to induction of anaesthesia
Single lumbar intrathecal injection of preservative-free morphine
• 200 mcg , or 300 mcg for upper gastrointestinal surgery, in 2 - 4 ml 0.5% bupivacaine
Lumbar epidural catheter inserted, labelled and capped
o Intravenous fentanyl PCA (fPCA) post op with 10 – 20 mcg bolus / 5 - 10 minute lockout
o After 24 hours Acute Pain Service (APS) to test the epidural with 4 ml 2% lignocaine with 1 in 200000 Adrenaline to ensure correct placement with onset of a sensory block, and exclusion of spinal block
o APS to administer 3 mg of epidural morphine with 3 ml normal saline 0.9% flush.
o APS to repeat epidural bolus 12 – 24 hourly up until 5 days post procedure if required as long as pain NRS is 3 or greater at the time of review
• Intravenous fentanyl PCA to continue whilst epidural in-situ
• Rescue analgesia for NRS pain score > 4
o Contact APS, to consider clinical situation, no restrictions as per protocol
o APS to consider the clinical situation and the following options first, prior to following local protocols to control pain
- Recommencing IV fPCA if ceased
- Epidural bolus fentanyl 50 mcg
- Oral analgesic including opioids
o Following rescue analgesia, respiratory observations every 30 minutes for the two hours after administration, then back to hourly PCA observations
• If sedation score > 2 or RR < 8, remove intravenous fentanyl PCA, alert medical team and consider naloxone administration.
• Epidural site must be checked twice daily. Should fever, or signs of local site infection occur, the epidural catheter must be removed following timing of anticoagulation confirmed, and consultation with APS

Protocol adherence will be determined following completion of patient follow up at 30 days upon review of the electronic medical record
Intervention code [1] 323339 0
Treatment: Drugs
Comparator / control treatment
Control group
Single lumbar intrathecal injection of preservative-free morphine prior to induction of anaesthesia
• 200 mcg , or 300 mcg for upper gastrointestinal surgery in 2 - 4 ml 0.5% bupivacaine
o Intravenous fentanyl PCA (fPCA) post op with 10 – 20 mcg bolus / 5 - 10 minute lockout
Control group
Active

Outcomes
Primary outcome [1] 331024 0
To measure the ability to recruit eligible patients into the study. Surveillance of surgical booking schedules will be used to screen for eligible patients. Criteria: The study protocol will be assessed as feasible if a recruitment rate of 50% of patients approached following the screening process is achieved. A record of those screened, approached and successfully recruited will be kept.
Timepoint [1] 331024 0
12 months after recruitment is commenced
Primary outcome [2] 331025 0
To measure the ability to successfully deliver each of the analgesic techniques according to the research protocol. Criteria: The study protocol will be assessed as feasible if a successful delivery rate, without the need for cross-over, of at least 80% is achieved. Confirmation of protocol adherence will be obtained through audit of the electronic medical record, confirming administration of intrathecal morphine, the use of fentanyl IV PCA and epidural morphine administration in the intervention group when clinical appropriate.
Timepoint [2] 331025 0
Postoperative day 5
Secondary outcome [1] 408516 0
Patient recovery as assessed by QoR-15
Timepoint [1] 408516 0
Measure QoR-15 on postoperative day 1
Secondary outcome [2] 408518 0
Oral opioid equivalent consumption assessed by analysis of electronic medical record and PCA machine analytics
Timepoint [2] 408518 0
Cumulative daily amount up until postoperative day 5, or discharge if occurring earlier, as well as, hourly usage in relation to epidural morphine bolus, defined as 0-6hrs, 6-12hrs, 12-18hrs and 18-24hrs.
Secondary outcome [3] 408519 0
Length of hospital stay as assessed by time from operation to discharge home. Data will be obtained from hospital records
Timepoint [3] 408519 0
At time of discharge home or to another non-acute care facility
Secondary outcome [4] 408520 0
Rest pain scores using numerical rating scale
Timepoint [4] 408520 0
In Post Anaesthetics Care Unit (PACU) and daily, recording the highest score for the previous 24hours
Secondary outcome [5] 408521 0
Sedation score using a sedation score scale
Timepoint [5] 408521 0
Recorded in the postanaesthetic care unit and the daily, recording the highest score for the previous 24 hours
Secondary outcome [6] 408522 0
Patient subjective experience of analgesia assessed using open ended questions.

Timepoint [6] 408522 0
Prior to discharge from hospital
Secondary outcome [7] 408523 0
Medical staff perspective on management of recruited patients measured using a short open ended questionnaire designed for this study
Timepoint [7] 408523 0
Immediately following completion of study recruitment
Secondary outcome [8] 408524 0
Distress level due to nausea, pruritus and pain using assessed using a numerical rating score.
Timepoint [8] 408524 0
In PACU and once per day whilst an inpatient through to day 5
Secondary outcome [9] 408525 0
Respiratory depression as assess by respiratory rate <8 breaths per minute, oxygen saturations <90% or need to airway intervention or naloxone administration
Timepoint [9] 408525 0
Any time point during admission post procedure until discharge from hospital
Secondary outcome [10] 408526 0
Pruritus score as assessed by numerical rating score.
Timepoint [10] 408526 0
In PACU and once per day whilst an inpatient through to day 5, recording highest score over previous 24 hours
Secondary outcome [11] 408527 0
Hypotension measured invasive monitoring i.e. arterial line, or non invasive e.g. sphygmomanometer, requiring intravenous fluid bolus or vasopressor
Timepoint [11] 408527 0
Any time point during admission post procedure until discharge from hospital
Secondary outcome [12] 408528 0
Cumulative time/number of visits required of acute pain service to manage patients having epidural morphine determined through audit of electronic medical record identifying the APS consultations
Timepoint [12] 408528 0
Until post operative day 5
Secondary outcome [13] 408670 0
Dynamic pain scores using numerical rating scale
Timepoint [13] 408670 0
In Post Anaesthetics Care Unit (PACU) and daily, recording the highest score for the previous 24hours

Eligibility
Key inclusion criteria
Eligible patients will be;
• > 18 years old
• Patients scheduled for elective major (> 2 hours surgical time) open abdominal surgery
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age >75 years
• Hypersensitivity reactions to any of the study drugs
• Contraindication to neuraxial (local site concerns, coagulopathy or untreated sepsis)
• Patient decline or inability to consent
• Cognitive impairment or language proficiency leading to inability to complete QoR-15 questionnaire or understand the pain scores
• Chronic pain, including baseline opioid use prior to hospital admission
• Contraindication to intrathecal morphine
• Lactating or pregnant women

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Computer generated randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A formal sample size calculation has not been done, given this is a feasibility study and considering the characteristics of the study’s objectives. A year-long trial period is anticipated, with plans for around 80-100 patients to be enrolled. Hence, there will be approximately 40-50 patients in each arm.

Data will be expressed as percentages, means with standard deviations, and/or medians with interquartile ranges. Group comparisons will be described by point estimates with 95% confidence intervals.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2022
Actual
25/10/2022
Date of last participant enrolment
Anticipated
30/11/2023
Actual
Date of last data collection
Anticipated
30/12/2023
Actual
Sample size
Target
80
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22175 0
The Alfred - Melbourne
Recruitment hospital [2] 22176 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 37327 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 311192 0
Hospital
Name [1] 311192 0
Alfred Hospital
Country [1] 311192 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road, Prahran, 3004, Victoria
Country
Australia
Secondary sponsor category [1] 312563 0
None
Name [1] 312563 0
Address [1] 312563 0
Country [1] 312563 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310724 0
Alfred Hospital Human Ethics Research Committee
Ethics committee address [1] 310724 0
Department of Anaesthesiology and Perioperative Medicine, 55 Commercial Road, Prahran, 3004, Victoria
Ethics committee country [1] 310724 0
Australia
Date submitted for ethics approval [1] 310724 0
02/05/2022
Approval date [1] 310724 0
13/09/2022
Ethics approval number [1] 310724 0

Summary
Brief summary
Major abdominal surgery is a common procedure associated with significant postoperative pain and morbidity. Poorly controlled pain negatively impacts upon recovery following surgery. Intrathecal morphine is an increasingly popular alternative analgesic option in major abdominal surgery but has a limited duration of effect. Epidural morphine can be continued postoperatively for as long as the epidural catheter remains in situ. A direct comparison of epidural morphine and intravenous opioid PCA following preoperative intrathecal morphine for major abdominal surgery has not been conducted.
We believe epidural morphine will be superior to intravenous opioid PCA in terms of quality of recovery, cost saving and opioid-sparing in the context of similar or lower side effects. The results of this preliminary feasibility study will be used to design a large-scale phase III, multicentre trial with the objective of obtaining outcomes that will accurately inform clinical practice
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118646 0
Dr Katrina Pirie
Address 118646 0
Alfred Health
55 Commercial Road,
Prahran, 3004, Victoria
Country 118646 0
Australia
Phone 118646 0
+61 3 9076 3176
Fax 118646 0
Email 118646 0
[email protected]
Contact person for public queries
Name 118647 0
Katrina Pirie
Address 118647 0
Alfred Health
55 Commercial Road,
Prahran, 3004, Victoria
Country 118647 0
Australia
Phone 118647 0
+61 3 9076 3176
Fax 118647 0
Email 118647 0
[email protected]
Contact person for scientific queries
Name 118648 0
Katrina Pirie
Address 118648 0
Alfred Health
55 Commercial Road,
Prahran, 3004, Victoria
Country 118648 0
Australia
Phone 118648 0
+61 3 9076 3176
Fax 118648 0
Email 118648 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Specific requests for de-identified data collected
When will data be available (start and end dates)?
Following completion, data analysis and publication and for up to 10 years
Available to whom?
Upon request following submission to ethics and with a statistical analysis plan
Available for what types of analyses?
As per statistical plan of those applying for the data
How or where can data be obtained?
Upon request as above, email [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.