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Trial registered on ANZCTR


Trial ID
ACTRN12613000983707
Ethics application status
Approved
Date submitted
30/08/2013
Date registered
4/09/2013
Date last updated
24/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A controlled comparison of three anaesthetic techniques for the total knee replacement surgery
Scientific title
A double blinded, randomised, controlled proof of concept study to compare postoperative analgesic and
mobilisation outcomes of local infiltration analgesia, single shot femoral nerve block and intrathecal morphine in
primary total knee arthroplasty
Secondary ID [1] 283119 0
Nil
Universal Trial Number (UTN)
U1111-1147-4065
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain requiring analgesia following elective total knee replacements. 289967 0
Osteoarthritis of the knee requiring elective total knee replacement 289968 0
Condition category
Condition code
Anaesthesiology 290338 290338 0 0
Pain management
Musculoskeletal 290357 290357 0 0
Osteoarthritis
Surgery 290358 290358 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study Arm-1 Local Infiltration Analgesia Randomized Arm
2.5mL of 0.5% bupivacaine (heavy) placed in the intrathecal space using a 25G Whitacre needle.
Ultrasound identification of the femoral nerve and direct guidance of a needle to deposit 20mL of normal saline around the femoral nerve. This will be performed after the spinal anaesthetic to minimize patient discomfort.
Intraoperative local infiltration of ropivacaine 0.2% into the knee joint through an indwelling catheter. This is injected under direct vision into all tissues traumatized during the operation.

Study Arm-2 Single Shot Femoral Nerve Block Randomized Arm
2.5mL of 0.5% bupivacaine (heavy) and placed in the intrathecal space using a 25G Whitacre needle.
Ultrasound identification of the femoral nerve and direct guidance of a needle to deposit 20mL 0.2% ropivacaine around the femoral nerve. This will be performed after the spinal anaesthetic to minimize patient discomfort.
Intraoperative local infiltration of normal saline into the knee joint through an indwelling catheter. This is injected under direct vision into all tissues traumatized during the operation.

Study Arm-3 Spinal Anaesthesia i.e. intrathecal Morphine Randomized Arm
2.5mL of 0.5% bupivacaine (heavy) and 200mcg Intrathecal morphine hydrochloride placed in the intrathecal space using a 25G Whitacre needle.
Ultrasound identification of the femoral nerve and direct guidance of a needle to deposit 20mL of normal saline around the femoral nerve. This will be performed after the spinal anaesthetic to minimize patient discomfort.
Intraoperative local infiltration of normal saline into the knee joint through an indwelling catheter. This is injected under direct vision into all tissues traumatized during the operation.
All study arms will employ Elastomeric Infusion in accordance with the standard TKR protocol followed by RGH.
Intervention code [1] 287839 0
Treatment: Drugs
Intervention code [2] 287840 0
Treatment: Surgery
Comparator / control treatment
The comparators for this trial are included in the 3 interventional arms for this trial. It is randomisation of participants to one of the three analgesic arms displayed in Descriptions of intervention(s)/exposure.
Control group
Active

Outcomes
Primary outcome [1] 290373 0
The primary objective of the study is to compare analgesic outcomes associated with total knee arthroplasty with three routinely used anesthetic techniques. This pain is assessed by way of opiod medication recieved by the patient in their post-operative time, and pain scores (Pain numerical rating scale (NRS)).
Timepoint [1] 290373 0
Surgery through to discharge at the following time points: 4hrs, 24 hrs, 48 hrs postoperatively.
Secondary outcome [1] 304370 0
Assess and compare the mobilization outcomes associated with total knee arthroplasty with three routinely used anesthetic techniques, timed up and go test, Knee injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score, and the Oxford Knee Score.
Timepoint [1] 304370 0
preadmission to establish a baseline for the patient.
4hrs post-operatively
24hrs post-operatively
48 hrs post-operatively
6 weeks post-operatively
Secondary outcome [2] 304371 0
To compare any adverse effects attributable to the interventions used in the randomization arms. eg, recording of nausea and/or vomiting, frequency and duration. There are documented in patient case report forms.
Timepoint [2] 304371 0
Surgery
4 hrs post-operatively
24 hrs post-operatively
48 hrs post-operatively
6 weeks post-operatively

Eligibility
Key inclusion criteria
Elective primary unilateral total knee arthroplasty
Age 40-75 years
BMI <40
Ability to self-mobilize
Patient understands the conditions of the study and are willing and able to give written informed consent to participate in the study including prescribed follow-ups
Patient is of legal age and skeletally mature
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous involvement in this study
Neuropathic pain or opioid tolerance (defined as use of >30mg oral morphine/day or equivalent – fentanyl patch 12mcg/hr., buprenorphine patch 20mcg/hr., oral oxycodone >20mg/day)
Patient has an emotional or neurological condition that would pre-empt their willingness to participate in the study including mental illness, intellectual disability, and drug or alcohol abuse.
Sensory and/or motor disorders in the operated limb, history of stroke of major neurological deficit.
Contraindication to spinal anaesthesia (coagulopathy, sepsis, local infection, patient refusal, spinal defects, previous laminectomy)
Contraindication to femoral nerve block (patient refusal, local infection, femoral neuropathy)
Patient is immunosuppressed or receiving high doses of corticosteroids.
Contraindication to NSAIDs (allergy, moderate to severe renal insufficiency).

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)
Potential clinical study participants will be identified from the TKR Waiting list.
Patients considered suitable for potential study enrolment will be contacted by the IMRI clinical research team to ascertain their level of interest in participating in this study.
A randomization code based on a pre-determined randomization schedule shall be performed by the RGH Pharmacy for each consented and eligible clinical study participant. The surgeon(s), anaesthetist(s), theatre staff, ward staff and acute pain team will be blinded to the treatment group.
Each clinical study participant will be given a study number during their preoperative orthopaedic clinic appointment.
The randomization code will assign the clinical study participant to one of the following study arms:
Study Arm-1 Local Infiltration Analgesia
Study Arm-2 Single Shot Femoral Nerve Block
Study Arm-3 Intrathecal morphine

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization schedule will be generated using the excel randomization software. This software has been checked by the research technical officer at FMC (Dylan De Los Angeles). Random number generators used by Excel are robust and have previously been endorsed by the US Government.
By using a double blinded, randomised, controlled study design, neither the surgeon nor anaesthetist will choose which of the analgesia methods are employed for a particular patient.
In accordance with the randomization schedule RGH Pharmacy shall prepare the drugs needed for each study participant. On the day of surgery, the anaesthetist will prepare the necessary solutions containing either the ropivacaine mixture or saline, morphine or saline). These solutions will be labeled only as study drug and with the participant’s randomization ID number.
The randomization schedule of Clinical Study Participants will be kept in two locations for the duration of the study and will only be viewed routinely by Pharmacy for dispensing of the study medication.
Location 1 – RGH pharmacy for allocation of study drugs and for pharmacist reference when receiving a script from the Anaesthetist for a study participant.
Location 2 – IMRI Quality Manager will be given a copy of the randomization identification list for breaking of the blinding procedure should it be required during the trial. The IMRI Quality Manager will only need to view the randomization should he be asked to by the Principal Investigator, Co-Investigators and/or treating medical officer of the trial participant.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis
Analysis of data will be via one-way ANOVA tests to detect differences between the group mean data, with post-hoc Tukey’s HSD test to determine where the difference lies if one exists. As this is a pilot study the sample size was given to assess whether any difference between the groups can be shown, as well as a proof of concept. From this result we can them perform a more accurate power calculation for sample size in a full study.

Recruitment
Recruitment status
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)
SA

Funding & Sponsors
Funding source category [1] 287871 0
Charities/Societies/Foundations
Name [1] 287871 0
International Musculoskeletal Research Institute
Address [1] 287871 0
Level 1, B-Block,
The Repatriation General Hospital,
Daws Rd,
Daw Park,
SA 5041
Country [1] 287871 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
International Musculoskeletal Research Institute
Address
Level 1, B-Block,
The Repatriation General Hospital,
Daws Rd,
Daw Park,
SA 5041
Country
Australia
Secondary sponsor category [1] 286598 0
None
Name [1] 286598 0
none
Address [1] 286598 0
None
Country [1] 286598 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289813 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 289813 0
The Flats G5 – Rooms 3 and 4
Flinders Drive
Flinders Medical Centre, Bedford Park SA 5042
Ethics committee country [1] 289813 0
Australia
Date submitted for ethics approval [1] 289813 0
26/08/2013
Approval date [1] 289813 0
30/08/2013
Ethics approval number [1] 289813 0
393.13

Summary
Brief summary
During Knee replacement surgery there are different techniques that the doctor can use to anaesthetise the patient during their surgery and differing options for managing pain relief immediately following surgery. The aim of this study is to compare 3 ways of doing this and to work out which way is best by looking at the pain relief needed by the patients in the different groups after their surgery. The 3 different ways are:
1. Locally Administered Anaesthesia
2. Spinal Anaesthesia
3. Femoral Nerve Block
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42566 0
Dr Chris Wilson
Address 42566 0
Department of Orthopaedics, Repatriation General Hospital, Daws Road, Daw Park SA 5041
Country 42566 0
Australia
Phone 42566 0
+61 8 8275 1753
Fax 42566 0
Email 42566 0
chris.wilson@health.sa.gov.au
Contact person for public queries
Name 42567 0
Ms Anneka Stephens
Address 42567 0
International Musculoskeletal Research Institute (IMRI),
Level-1,
B-Block,
Repatriation General Hospital,
Daws Rd
Daw Park,
SA 5041
Country 42567 0
Australia
Phone 42567 0
+61 8 8275 1751
Fax 42567 0
Email 42567 0
anneka.stephens@imri.org.au
Contact person for scientific queries
Name 42568 0
Ms Anneka Stephens
Address 42568 0
IMRI,
Level-1,
B-Block,
Repatriation General Hospital,
Daws Rd
Daw Park,
SA 5041
Country 42568 0
Australia
Phone 42568 0
+61 8 8275 1751
Fax 42568 0
Email 42568 0
anneka.stephens@imri.org.au