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Trial registered on ANZCTR


Registration number
ACTRN12613001036707
Ethics application status
Approved
Date submitted
16/09/2013
Date registered
18/09/2013
Date last updated
18/09/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomised prospective, double-blinded study comparing the effectiveness of administering morphine patient controlled analgesia (PCA) to morphine and ketamine PCA for patients undergoing a total knee replacement.
Scientific title
In patients undergoing a total knee replacement, does adding ketamine to a morphine patient controlled analgesia (PCA) lead to improved analgesia as measured by VNRS? A randomised, prospective, double-blinded study.
Secondary ID [1] 283227 0
Nil known
Universal Trial Number (UTN)
U1111-1148-0975
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain after Total Knee Replacement 290099 0
Ketamine in patient controlled analgesia side effects 290100 0
Morphine patient controlled analgesia side effects 290101 0
Condition category
Condition code
Anaesthesiology 290476 290476 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A Morphine 1mg/mL + Ketamine 2mg/mL patient controlled analgesia (PCA) administered intravenously, with 5 minute lockout, and 10mL hourly limit to be commenced after adequate pain relief is achieved in recovery with a verbal numerical rating scale of <4, post total knee replacement. PCA to cease at the discretion of the Acute Pain Service as is the usual protocol at the institution of this study, usually 48 hours postoperatively.
Intervention code [1] 287957 0
Treatment: Drugs
Comparator / control treatment
Morphine 1mg/mL patient controlled analgesia (PCA) administered intravenously, with 5 minute lockout, and 10mL hourly limit to be commenced after adequate pain relief is achieved in recovery with a verbal numerical rating scale of <4, post total knee replacement. PCA to cease at the discretion of the Acute Pain Service as is the usual protocol at the institution of this study, usually 48 hours postoperatively
Control group
Active

Outcomes
Primary outcome [1] 290503 0
Patient pain scores measured by the Verbal numerical rating scale for pain (VNRS) 0 - 10, commencing at discharge from recovery until 48 hours post surgery.
Timepoint [1] 290503 0
Median pain scores for each patient at day 0, day 1 and day 2.
Secondary outcome [1] 304645 0
Side effects measured using a Yes/No questionnaire by the Acute Pain Service nurse. Specifically, these are: drowsiness, hallucinations, nausea, and pruritus.
Timepoint [1] 304645 0
Day 0, 1 and 2.
Secondary outcome [2] 304646 0
Patient satisfaction measured as a percentage out of 100%
Timepoint [2] 304646 0
24 hours and 48 hours
Secondary outcome [3] 304647 0
Total amount of patient controlled analgesia (PCA) solution used over 48 hours measured in mililitres
Timepoint [3] 304647 0
48 hours
Secondary outcome [4] 304648 0
Day patient mobilised measured as day post operatively
Timepoint [4] 304648 0
Day 1 or 2
Secondary outcome [5] 304649 0
Would patient use a patient controlled analgesia (PCA) system again, measured as a Yes/No questionnaire
Timepoint [5] 304649 0
48 hours

Eligibility
Key inclusion criteria
Elective patients undergoing a Total Knee Replacement
18 years or older
Would be able to understand the use of a Patient Controlled Analgesia (PCA) system
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
An allergy to morphine or ketamine
Patient inability to use a PCA
Pre-existing neurological or psychiatric illnesses
Evidence of severe cardiovascular, renal, hematologic or hepatic disease
Patients unsuitable for the study’s standardised anaesthetic technique
Patients requiring other analgesic drugs or regional techniques which may affect the appreciation of pain
Alcohol and opioid dependent patients
Patients with a history of chronic pain

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)
Following hospital ethics committee approval, all elective patients undergoing a TKR at The Wollongong Hospital from July 2004 are given an explanation of research activity and a patient information sheet by an independent medical officer, the Anaesthetic Registrar, at the peri-operative clinic. The patient's Anaesthetist on the day of surgery is to obtain written informed consent from the patient to enrol them in the trial.
Randomisation to occur in the Post Anaesthesia Care Unit (PACU) by the nurse looking after the patient, who is not involved in the study. The nurse is to draw the group allocation out of an opaque envelope in an area away from the patient, and prepare the appropriate PCA solution for the patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculations were based on a type I error of 0.05 and a type II error of 0.2, leading to a power of 0.8. An initial sample size of 100 (that is 50 for each of the main groups) was selected arbitrarily to indicate size of effect. Calculating Cohen’s D on this initial sample indicated a mean size of effect for Group 1 vs Group 2 (morphine vs morphine+ketamine PCA) of 17.6%, and for Group 1a vs Group 2a (morphine+NSAID vs morphine+ketamine+NSAID) of 17.0%. Thus the aim was the recruit 530 patients.

Recruitment
Recruitment status
Completed
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
Recruitment postcode(s) [1] 7364 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 287975 0
Hospital
Name [1] 287975 0
The Anaesthetic Department
The Wollongong Hospital
Address [1] 287975 0
The Anaesthetic Department
The Wollongong Hospital
Crown Street, Wollongong, New South Wales, 2500
Country [1] 287975 0
Australia
Primary sponsor type
Individual
Name
Yoon Leng Ooi
Address
The Anaesthetic Department, Level 4
St Vincent's Public Hospital
390 Victoria Street, Darlinghurst, New South Wales, 2010
Country
Australia
Secondary sponsor category [1] 286696 0
Individual
Name [1] 286696 0
Carol Jeffs
Address [1] 286696 0
The Anaesthetic Department
The Wollongong Hospital
Crown Street, Wollongong, New South Wales, 2500
Country [1] 286696 0
Australia
Secondary sponsor category [2] 286697 0
Individual
Name [2] 286697 0
Sonia Markocic
Address [2] 286697 0
Nurse Practitioner, Acute Pain Service
Level 8, Block C, The Wollongong Hospital
Crown Street, Wollongong, New South Wales, 2500
Country [2] 286697 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289902 0
University of Wollongong Human Research Ethics Committee
Ethics committee address [1] 289902 0
Research Services Office
Level 1, Building 20 Communications Centre
University of Wollongong, New South Wales, 2522
Ethics committee country [1] 289902 0
Australia
Date submitted for ethics approval [1] 289902 0
Approval date [1] 289902 0
Ethics approval number [1] 289902 0
HE04/115

Summary
Brief summary
Total Knee Replacements are associated with a frequent incidence of intense postoperative pain, particularly during early attempts at mobilisation. This trial will investigate the effective of adding Ketamine to a Morphine Patient Controlled Analgesia (PCA) system in order to improve analgesic efficacy, focusing on the first 48 hours. It will also measure side effects that might emerge from adding Ketamine to a Morphine PCA, the level of patient satisfaction with their PCA, and whether the addition of Ketamine leads to less PCA use.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42994 0
Dr Carol Jeffs
Address 42994 0
The Anaesthetic Department
The Wollongong Hospital
Crown Street, Wollongong, New South Wales, 2500
Country 42994 0
Australia
Phone 42994 0
+61 2 4222 5521
Fax 42994 0
+61 2 4222 5468
Email 42994 0
carolmjeffs@gmail.com
Contact person for public queries
Name 42995 0
Dr Carol Jeffs
Address 42995 0
The Anaesthetic Department
The Wollongong Hospital
Crown Street, Wollongong, New South Wales, 2500
Country 42995 0
Australia
Phone 42995 0
+61 2 4222 5521
Fax 42995 0
+61 2 4222 5468
Email 42995 0
carolmjeffs@gmail.com
Contact person for scientific queries
Name 42996 0
Dr Yoon Leng Ooi
Address 42996 0
The Anaesthetic Department
St Vincent's Public Hospital
390 Victoria Street, Darlinghurst, New South Wales, 2010
Country 42996 0
Australia
Phone 42996 0
+61 2 8382 3200
Fax 42996 0
Email 42996 0
yoonleng@hotmail.com

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary