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Trial registered on ANZCTR


Registration number
ACTRN12611001220954
Ethics application status
Approved
Date submitted
21/11/2011
Date registered
29/11/2011
Date last updated
18/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Tramadol vs. Morphine for refractory pain in the recovery room
Scientific title
Post-operative patients who have ongoing pain in the recovery room despite post-operative morphine will be randomized to receive either more morphine or tramadol and time to readiness to discharge from the recovery room will be measured.
Secondary ID [1] 273425 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative pain 279212 0
Condition category
Condition code
Anaesthesiology 279418 279418 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed study is to recruit patients from the post-operative recovery unit(PACU) who have ongoing pain despite receiving post-operative morphine. They would then be randomized to receive either tramadol or further morphine for their ongoing pain. The primary outcome measure would be time from first administration of study drug to readiness for discharge from the recovery room. Secondary outcome measures would be pain scores measured every 5 minutes while in the recovery room, total time spent in the recovery room and the presence or absence of opioid related side effects such as sedation, respiratory depression, nausea, vomiting while in the recovery room. The requirement and types of anti-emetic use while in recovery would also be recorded. There will be 2 active treatment groups, no placebo group. One group will receive morphine 1mg intravenous boluses titrated to a maximum of 10mg. They will receive the bolus's at 3-5 minute intervals up to a maximum of 10 bolus's or until the pain score is less than 3 (out of 10). The other group will receive Tramadol 10mg intravenous boluses titrated to a maximum of 100mg. They will receive the bolus's at 3-5 minute intervals up to a maximum of 10 bolus's or until the pain is less than 3 (out of 10).
Intervention code [1] 283760 0
Treatment: Drugs
Comparator / control treatment
There will be 2 active treatment groups, no placebo group. One group will receive morphine 1mg intravenous boluses titrated to a maximum of 10mg. This group will be considered the control group. The other group will receive Tramadol 10mg intravenous boluses titrated to a maximum of 100mg. Each group will receive a 1ml (1mg morphine or 10mg tramadol) bolus every 3-5 minutes up to a maximum of 10ml.
Control group
Active

Outcomes
Primary outcome [1] 285988 0
Time to readiness for discharge from recovery after entry into the study.
Timepoint [1] 285988 0
Discharge from recovery
Secondary outcome [1] 294903 0
Incidence of side effects, which are likely to include nausea and vomiting, dizziness and respiratory depression. Nausea and dizziness will be elicited by questioning. The vomiting will be recorded as present or absent, and the respiratory depression will be based on the respiratory rate which will be recorded every 5 minutes with the other observations.
Timepoint [1] 294903 0
During the study period while in recovery
Secondary outcome [2] 294904 0
Pain scores during the titration of the study drug. These will be recorded by a numerical rating scale every 5 minutes with the other observations.
Timepoint [2] 294904 0
During the study period while in recovery

Eligibility
Key inclusion criteria
- Major surgery
- American Society of Anesthesia (ASA) rating of 1 or 2 or 3
- Morphine based analgesia indicated post-operatively
- Adequate English language skills
- Adequate intellectual capacity
- Age between 18-80 years old
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient refusal
- Allergy to either morphine or tramadol
- Chronic opioid use
- Severe chronic pain
- Epilepsy
- Pregnancy
- Depression requiring treatment with monoamine oxidase inhibitor or selective serotonin reuptake inhibitor (SSRI)
- Severe renal or hepatic impairment
- Expected to be intubated and ventilated electively post-operatively

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)
All healthy patients who are coming for major surgery would be eligible to participate in the study. Recruitment of the patients and the informed consent process would take place pre-operatively. Conduct of the anaesthetic would be entirely at the discretion of the attending anaesthetist. Once in the patients were in the recovery room they would receive standard recovery room cares. This care includes monitoring of pain scores and titration of morphine 1-2mg IV each 3-5 minutes (up to 10mg) to achieve patient comfort. If any patient had a pain score greater than 5 at rest 5 minutes after the last dose of morphine then they would then enter the study. At this point they would be randomised by toss of coin to receive either further morphine (titrated dose up to 10mg more) or tramadol (titrated dose up to 100mg) until pain was controlled. The syringes that the study drug is made up in will be labelled study drug one or two. Therefore the recovery nurses will be blinded to which drug they are giving. If after this period of further drug titration a patient’s pain score remains greater than 5 then the attending anaesthetist would take over management of that patient’s pain. The outcome measure (time to readiness to discharge from recovery) would be determined by the recovery nurse by scoring patients of a 14 point recovery score where they have to score 13/14 to be eligible for discharge.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The study drugs will be made up in pre-filled syringes which will be labelled study drug 1 or 2, but not labelled with which drug they contain. On meeting the criteria for entry to the study (i.e.having received 10mg of morphine post-operatively) the recovery nurse will enter the patient in the study. A coin will be flipped for each patient, and if tails appears then the patient will receive study drug one and if heads comes up then the patient will receive study drug 2.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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 outside Australia
Country [1] 3969 0
New Zealand
State/province [1] 3969 0
Waikato

Funding & Sponsors
Funding source category [1] 284236 0
Hospital
Name [1] 284236 0
Anaesthetic department, Waikato hospital
Address [1] 284236 0
Pembroke St
Hamilton
Waikato 3204
Country [1] 284236 0
New Zealand
Primary sponsor type
Individual
Name
Kelly Byrne
Address
C/- Anaesthetic department,
Waikato hospital,
Pembroke St
Hamilton
Waikato 3204
Country
New Zealand
Secondary sponsor category [1] 269192 0
Individual
Name [1] 269192 0
Professor Jamie Sleigh
Address [1] 269192 0
c/- Anaesthetic department
Waikato Hospital
Pembroke St
Hamilton
Waikato 3204
Country [1] 269192 0
New Zealand
Other collaborator category [1] 260358 0
Individual
Name [1] 260358 0
Dr John Barnard
Address [1] 260358 0
C/- Anaesthetic department
Waikato hospital
Pembroke St
Hamilton
Waikato 3204
Country [1] 260358 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286201 0
Northern Y Ethics committee
Ethics committee address [1] 286201 0
3rd floor, BNZ building
354 Victoria St
PO Box 1031
Hamilton
Ethics committee country [1] 286201 0
New Zealand
Date submitted for ethics approval [1] 286201 0
23/11/2011
Approval date [1] 286201 0
26/03/2012
Ethics approval number [1] 286201 0

Summary
Brief summary
Objective

The objective of this study is to determine whether patients who have ongoing post-operative pain despite administration of morphine in the recovery room respond better to tramadol than to further morphine.

Hypothesis

Our hypothesis is that there will be no difference in the time to readiness to discharge from recovery in those patients who receive either morphine or tramadol for ongoing post-operative pain in the recovery room.

Methods

All healthy patients who are coming for major surgery would be eligible to participate in the study. Recruitment of the patients and the informed consent process would take place pre-operatively. Conduct of the anaesthetic would be entirely at the discretion of the attending anaesthetist. Once in the patients were in the recovery room they would receive standard recovery room cares. This care includes monitoring of pain scores and titration of morphine 1-2mg IV each 5 minutes (up to 10mg) to achieve patient comfort. If any patient had a pain score greater than 5 at rest 5 minutes after the last dose of morphine then they would be randomised to receive either further morphine (titrated dose up to 10mg more) or tramadol (titrated dose up to 100mg) until pain was controlled. If after this period of further drug titration a patient’s pain score remained greater than 5 then the attending anaesthetist would take over management of that patient’s pain.

The recovery room nurses would be blinded to the group allocation of the patients. The medications will be provided in identical pre-mixed syringes labelled to identify the study but not the drug contained. Each study syringe would contain 10 ml of fluid, either morphine 10mg/10ml or tramadol 100mg/10ml. Previous work has suggested that the conversion ratio between the 2 medications is between 8.5:1 and 11:1 .

Data will be collected from the recovery room observations, which include pain scores, vital sign observations and administration of anti-emetics and observations whether or not the patient is feeling nauseous or is vomiting. Time to readiness for discharge will be measured from the time the patient receives the first dose of the study medication to the time that they meet the recovery room criteria for discharge.

The proportion of patients failing to meet discharge criteria in each arm of the study will be compared and the reasons why they did not meet the criteria analysed. The proportion of patients who did not receive study drugs will be recorded and their time in recovery will provide a comparator to those whose pain was difficult to control.

Inclusion criteria
- Major surgery
- ASA 1 or 2 or 3
- Morphine based analgesia indicated post-operatively
- Adequate English language skills
- Adequate intellectual capacity
- Age between 18-80 years old

Exclusion criteria
- Patient refusal
- Allergy to either morphine or tramadol
- Chronic opioid use
- Severe chronic pain
- Epilepsy
- Pregnancy
- Depression requiring treatment with monoamine oxidase inhibitor or SSRI
- Severe renal or hepatic impairment
- Expected to be intubated and ventilated electively post-operatively

Analysis

Time to readiness to discharge and mean pain scores will be compared with a 2-tailed student t-test. Presence of side effects will be compared with Chi squared testing. Other data will be presented as mean and standard deviation where appropriate.

A power analysis using an alpha value of 0.05 and a beta value of 0.8 yielded a sample size of 43 patients for each group. Accounting for potential drop outs and incomplete data collection we aim to enrol 50 patients in each group for a total of 100 patients.
Trial website
Nil
Trial related presentations / publications
Byrne K, Nolan A, Barnard J, Tozer M, Harris D, Sleigh J. Managing Postoperative Analgesic Failure: Tramadol Versus Morphine for Refractory Pain in the Post-Operative Recovery Unit. Pain Med. 2017 Feb 1;18(2):348-355.
doi: 10.1093/pm/pnw084.
Public notes
Attachments [1] 2383 2383 0 0

Contacts
Principal investigator
Name 33418 0
Dr Kelly Byrne
Address 33418 0
c/- department of anaesthesia, Waikato hospital, Pembroke Street, Hamilton 3200, NZ
Country 33418 0
New Zealand
Phone 33418 0
+642102224390
Fax 33418 0
Email 33418 0
kpa.byrne@gmail.com
Contact person for public queries
Name 16665 0
Dr Kelly Byrne
Address 16665 0
c/- Anaesthetic department
Waikato hospital
Pembroke Street
Hamilton 3204
Country 16665 0
New Zealand
Phone 16665 0
+6478398899
Fax 16665 0
Email 16665 0
kpa.byrne@gmail.com
Contact person for scientific queries
Name 7593 0
Dr Kelly Byrne
Address 7593 0
c/- Anaesthetic department
Waikato hospital
Pembroke Street
Hamilton 3204
Country 7593 0
New Zealand
Phone 7593 0
+6478398899
Fax 7593 0
Email 7593 0
kpa.byrne@gmail.com

No information has been provided regarding IPD availability
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