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Trial registered on ANZCTR


Registration number
ACTRN12613000806763
Ethics application status
Approved
Date submitted
17/07/2013
Date registered
22/07/2013
Date last updated
31/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized trial of sevoflurane versus desflurane on the quality of recovery following knee arthroscopy
Scientific title
A randomized trial of sevoflurane versus desflurane on the quality of recovery following knee arthroscopy
Secondary ID [1] 282838 0
nil
Universal Trial Number (UTN)
U1111-1145-7074
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
recovery following knee arthroscopy 289645 0
Condition category
Condition code
Anaesthesiology 289964 289964 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Common management for both groups will include the following:

1. Pre-medication other than oral analgesic (such as paracetamol) will not be used.
2. Induction will be with intravenous propofol (50-200mg), including co-induction consisting of fentanyl 25-100 micrograms and midazolam 1-5 mg. Antimemetics including dexamethasone and 5HT3 antagonists (such as ondansetron) may be administered by the treating anaesthetist.
3. Analgesia will consist of intraoperative opiates, 1 g paracetamol orally four times per day, intravenous opiates during early recovery (such as fentanyl up to 30 mionutes after surgery), Morphine 2.5-10mg subcutaneously 3 hourly, or oral oxynorm 10-20mg 6 hourly will be used for breakthrough analgesia. NSAIDs including Cox II inhibitors (such as paracoxib 40mg intravenously may be used.
4. Patients will not be included in the study if the treating anaesthetist considers that a regional anaesthetic rather than a general anaesthetic would be in the best interest of the patient. This would most likely be a spinal anaesthetic.

Intervention drug.
Following induction of general anaesthesia either desflurane or sevoflurane via inhalation will be introduced as the maintenance anaesthetic and titrated to maintain an adequate clinical depth of anaesthesia for the remainder of the operation and stopped after the last skin stitch is completed. Typically this will involve inhaled anaesthetic concentrations of 6% desflurane and 2.0% sevoflurane, reflecting the different potencies of the drugs. If Bispectral index monitoring (depth of anaesthesia monitor) is available, the target range is 40-60.
Intervention code [1] 287530 0
Treatment: Drugs
Comparator / control treatment
Comparison of two anaesthetic agents - sevoflurane and desflurane
Control group
Active

Outcomes
Primary outcome [1] 290016 0
Quality of recovery, as measured by the postoperative quality recovery scale (PQRS) at Day 3 for recovery in all of the individual recovery domains (all domains recovery).
Timepoint [1] 290016 0
Day 3 postoperative
Secondary outcome [1] 303779 0
Recovery for all domains measured by the postoperative quality of recovery scale (PQRS) at the other time points of measurement (15 minutes, 40 minutes 1 day, 3 days and 3 months following cessation of anaesthesia).
Timepoint [1] 303779 0
15 minutes, 40 minutes 1 day, 3 days and 3 months following cessation of anaesthesia

Eligibility
Key inclusion criteria
1. Adult patients undergoing knee arthroscopy surgery under general anaesthesia
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are not fluent in English will be excluded, as they may be unable to answer the recovery questionnaire adequately.
2. Patients undergoing regional anaesthesia only.
3. Unable to give informed consent.

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)
Concealment will be by placing the card containing the allocation information in double opaque sealed envelopes, and concealment will be maintained until after recruitment and the patients is admitted into the operating theatre. The treating anaesthetist will then open the envelopes to reveal the allocation. A non-participant in any process of the study will perform preparation of the envelopes. A copy of the randomization sequence will be stored in a separate databank, which is password protected and not available to the investigators until the study is complete.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization sequence will by produced using a computer generated randomization sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary endpoint will be assessed using a comparison of two proportions. Recovery profiles over time will be compared using the Cochran Mantel Haenszel test for repeated measurement of proportions, and will test the global hypothesis for difference between groups over time.

Sample-size estimates are based on the pilot data for all domains recovery at day 3 (desflurane 35.2% vs. sevoflurane 20%) and using Fisher’s exact method test to determine a difference of 10% difference in the total score using a 2-tailed test with 80% power at a P=0.05 significance. The minimal sample size is 137 for each group. This will be increased to 150 patients per group to account for potential non-completions.

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)
VIC
Recruitment hospital [1] 1317 0
Epworth Richmond - Richmond
Recruitment hospital [2] 1318 0
Epworth Eastern Hospital - Box Hill

Funding & Sponsors
Funding source category [1] 287620 0
Self funded/Unfunded
Name [1] 287620 0
Address [1] 287620 0
Country [1] 287620 0
Primary sponsor type
University
Name
The University of Melbourne
Address
Grattan Street Parkville VIC 3010
Country
Australia
Secondary sponsor category [1] 286363 0
None
Name [1] 286363 0
Address [1] 286363 0
Country [1] 286363 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289589 0
Epworth Hospital HREC
Ethics committee address [1] 289589 0
Ethics committee country [1] 289589 0
Australia
Date submitted for ethics approval [1] 289589 0
Approval date [1] 289589 0
18/07/2013
Ethics approval number [1] 289589 0

Summary
Brief summary
Aims: To identify whether the quality of recovery over time is affected by sevoflurane versus desflurane when used as the primary anaesthetic for knee arthroscopy surgery.

Significance: Quality of recovery is an emerging field within anaesthesia of great importance. Although large outcome studies are very important in anaesthesia, there is a changing focus from “mortality and morbidity studies”, to quality of recovery. The reason is that the frequency of mortality is now very low with the result that few interventions will further reduce mortality. Very large numbers are required to demonstrate any improvements in surgery and anaesthesia when mortality is used as an outcome. However early data on the PQRS as well as clinical reports indicate that the quality of recovery is often poor in many patients, and yet these are not identified by the treating anaesthetist. There are implications for the individual patient, for the practice of anaesthesia, and for the community (such as safe return to work or to driving). Knee arthroscopy is often performed as an outpatient (day) procedure, and therefore may be perceived as “minor surgery”. However, for some patients the quality of recovery including cognitive decline may be more profound than would be expected from brief peripheral surgery. The role of the anaesthetic agent may have an important influence on this recovery. It is frequently assumed by anaesthetists that anaesthetics from the same class should produce similar effects when administered for a brief anaesthetic, but there are insufficient data to validate that assumption. This study will help anaesthetists to choose the anaesthetic that is best for their patients undergoing brief surgery.

Hypothesis: The null hypothesis is that there is no difference in recovery in all domains measured using the PQRS, in patients undergoing knee arthroscopy under general anaesthesia with either sevoflurane or desflurane as the primary anaesthetic

Methods: A parallel group, randomised trial with 1:1 allocation ratio will be conducted in adult patients undergoing arthroscopy, where the intervention is to receive sevoflurane or desflurane as the primary anaesthetic agent. Quality of recovery will be measured using the Post-operative Quality of Recovery Scale (PQRS), at baseline (preoperative), 15 and 40 minutes, one and three days, and three months following surgery. Patients who are unable to complete the PQRS due to language limitations, or who will receive regional anaesthesia will be excluded. Recovery is defined as “return to baseline values or better” for each of the survey questions and is dichotomised to recovered or not recovered. Recovery is grouped within domains (physiological, emotive, nociceptive, cognitive, and activities of daily living, with a sixth domain of self-assessment). The primary endpoint will be the incidence of recovery for all domains (not including self-assessment) on the third day after surgery. Based on a pilot study performed at the Epworth Hospital, we estimate the ability to detect a clinically important difference with 150 patients in each group. Guidelines for other aspects of patient care including co-induction agents, antiemetics, and post-operative analgesics will be issued to reduce variability between patients.

Likely benefits: There are pharmacological differences between sevoflurane and desflurane that make them more or less attractive to the anesthetist. Desflurane, should provide for earlier and more complete recovery then sevoflurane, but sevoflurane is an easier drug to administer due to a lower incidence of airway irritability. There are very few data investigating quality of recovery with these two drugs beyond emergence and PACU care. This study will provide data into whether there are longer-term differences in the quality of recovery between these two drugs.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41470 0
Prof Colin Royse
Address 41470 0
The University of Melbourne
245 Cardigan St
Carlton, Vic 3053
Country 41470 0
Australia
Phone 41470 0
+61390354704
Fax 41470 0
Email 41470 0
colin.royse@unimelb.edu.au
Contact person for public queries
Name 41471 0
Prof Colin Royse
Address 41471 0
The University of Melbourne
245 Cardigan St
Carlton, Vic 3053
Country 41471 0
Australia
Phone 41471 0
+61390354704
Fax 41471 0
Email 41471 0
colin.royse@unimelb.edu.au
Contact person for scientific queries
Name 41472 0
Prof Colin Royse
Address 41472 0
The University of Melbourne
245 Cardigan St
Carlton, Vic 3053
Country 41472 0
Australia
Phone 41472 0
+61390354704
Fax 41472 0
Email 41472 0
colin.royse@unimelb.edu.au

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