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Trial registered on ANZCTR


Registration number
ACTRN12614000169640
Ethics application status
Approved
Date submitted
11/12/2013
Date registered
11/02/2014
Date last updated
8/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of Analgesia Nociception Index (ANI) guided analgesia administration with Standard Clinical Practice during Routine General Anaesthesia
Scientific title
Comparison of Analgesia Nociception Index (ANI) guided analgesia administration with Standard Clinical Practice during Routine General Anaesthesia on post-operative pain scores and post-operative opioid requirement in patients undergoing spinal surgery
Secondary ID [1] 283757 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Pain 290731 0
Condition category
Condition code
Anaesthesiology 291093 291093 0 0
Anaesthetics
Anaesthesiology 291094 291094 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed study aims to evaluate Analgesia Nociception Index (ANI) titrated analgesia in patients undergoing spinal surgery. The ANI Monitor examines small fluctuations in heart rate to determine the level of analgesia to nociception balance. This clinical utility study is designed to investigate the effect of ANI monitor guided fentanyl administration on post-operative events, including self-reported post-operative pain scores, analgesia administration, recovery times, and opioid-related side effects. The monitor will be applied prior to induction of anaesthesia and removed once the patient is ready for transfer to a general nursing ward. The study will also record the incidence of unwanted intra-operative events such as tachycardia, hypertension, and the consumption of fentanyl under constant hypnotic level balanced general anaesthesia.
Intervention code [1] 288443 0
Treatment: Devices
Comparator / control treatment
Standard Clinical Practice. This involves titrating fentanyl to traditional variables, such as heart rate, blood pressure, respiratory rate and surgical stimulus.
Control group
Active

Outcomes
Primary outcome [1] 291075 0
Post-operative pain scores using Numerical rating scales (NRS). Patients rate their pain intensity on the scale of 0 to 10 where 0 represents ‘no pain’ and 10 represents ‘worst pain
imaginable’. The Verbal NRS (VNRS) is administered using a phrase such as: ‘On ascale of 0 to 10, with 0 being no pain at all and 10 being the worst pain you could imagine, where would you rate the pain you are experiencing right now?
Timepoint [1] 291075 0
Within 1 hour of completion of surgery
Primary outcome [2] 291158 0
Post-operative fenanyl Consumption in micrograms (total) and micrograms per hour.
Timepoint [2] 291158 0
Until ready for discharge from PACU
Secondary outcome [1] 305970 0
Intra-operative hemodynamic disturbance.
a. Defined as a change in blood pressure < or > 20% of baseline as measured by a non-invasive blood pressure machine at 2.5 minutely intervals
b. Defined as a change in heart rate < or > 20% of baseline as measured via Electrocardiogram
c. Total time spent (total and %) within these limits and outside of these limits
Timepoint [1] 305970 0
Intra-operatively every 5 minutes.
Secondary outcome [2] 305972 0
Post-operative sedation scores with Ramsay Sedation Score.
Timepoint [2] 305972 0
5 minutely within 1 hour post-operatively
Secondary outcome [3] 305974 0
Post-operative opioid side-effects:
a. Nausea and vomiting: to measure the incidence of any nausea, emetic episodes (retching or vomiting), or both (i.e., postoperative nausea and vomiting) during the first 24 postoperative hours. Upon Discharge from PACU, and at 24 hours post surgery, patients will verbally rate their worst nausea episode since emergence on an 11-point scale, where 0 represented no nausea and 10 the most severe nausea.
b. Respiratory depression: respiratory rate recorded at 5 minute intervals. This will be done by the PACU nurse, counting the number of breaths the patient takes over a 30 second period and multiplying by 2. Requirement for naloxone reversal of opioids will be recorded.
c. Airway Obstruction: recorded as episodes of intervention, either manual support (jaw-thrust/chin lift) or devices used (oro-pharyngeal airway/nasopharyngeal airway)
Timepoint [3] 305974 0
Within 24 hours post-operatively
Secondary outcome [4] 305975 0
Post-operative time to discharge from Post Anaesthesia Care Unit (PACU)
Timepoint [4] 305975 0
Post-operative time to ready for discharge from Post Anaesthesia Care Unit (PACU)

Eligibility
Key inclusion criteria
Patients scheduled for non-emergent, spinal surgery, aged 18-75 years, American Society of Anesthesiologists (ASA) score 1 or 2, competent to consent to participation, able to use a Visual Analogue Scale (VAS) and able to activate a patient controlled analgesia (PCA) machine post-operatively.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Emergency surgery
Inability to consent, lack of written consent or speak English fluently
Pregnancy or lactation. Pregnancy test will be performed in all women of child bearing potential
Cardiac morbidity
Non-regular sinus cardiac rhythym
Cardiac disease which impacts usual daily functioning (equivalent to ASA greater than or equal to 3)
Implanted cardiac pacemaker
Concurrent medications with a major effect affect upon the sinus node
Expected duration of surgery greater than 3 hours (180 minutes)
Extremes of weight (Body Mass Index less than or equal to 19 or greater than or equal to 35 kg per meter squared)
Pre-operative chronic opioid use or chronic pain, equivalent to oxycodone 20mg per oral, per day for more than 6 weeks
Allergy or intolerance to any of the study drugs
Use of neuraxial anaesthesia

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)
Subjects are enrolled once inclusion and exclusion criteria have been checked and informed consent obtained. Allocation to placebo or active arms of the trial will involve contacting the holder of the allocation schedule who is at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation to treatment or standard clinical practice via random allocation using random permuted blocks (i.e. computerised sequence generation). Allocation to trial will be the randomisation point.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size estimation is based on the primary outcome (early post-operative pain scores). Post-operative pain will be measured by a numerical pain rating scale (NPRS) from 0-10. If we assume that ANI guided analgesia administration reduces the post-operative pain NPRS from 5 to 3, and a Standard Deviation equal to 4, then recruitment of 25 participants in each group will result in a statistical power (1-Beta) of 0.8 at an a error level of 0.05. The reduction of pain from a NPRS of 5 (moderate pain) to 3 (mild pain) has been chosen as a clinically significant improvement in clinical practice that would make the use of such a monitor clinically beneficial. This is supported by evidence that reduction in pain intensity by 30% to 35% from baseline has been rated as clinically meaningful by patients with postoperative pain. It has been shown recently in an observational study that the mean NPRS upon waking from anaesthesia was 5 following ENT and endoscopic proceedures and the standard deviation used in the sample size calculation has been taken from research examining NPRS post-operatively.

Previous studies from other investigators looking at the effect of intraoperative drug delivery and monitoring of analgesia and have required between 40-80 subjects. We believe that 50 subjects will be sufficient to detect a difference between the groups if one exists. We plan to recruit 30 participants to each group (Total 60) to allow withdrawals from the study and data failures.

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)
SA
Recruitment hospital [1] 1853 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 7636 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 288422 0
University
Name [1] 288422 0
The University of Adelaide
Address [1] 288422 0
The University of Adelaide
North Terrace
Adelaide SA 5000
Country [1] 288422 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
The University of Adelaide
North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 287127 0
None
Name [1] 287127 0
none
Address [1] 287127 0
Country [1] 287127 0
Other collaborator category [1] 277727 0
Individual
Name [1] 277727 0
Professor Guy Ludbrook
Address [1] 277727 0
Professor of Anaesthesia and Intensive Care
University of Adelaide
North Terrace
Adelaide SA 5000
Country [1] 277727 0
Australia
Other collaborator category [2] 277728 0
Individual
Name [2] 277728 0
Professor Jamie Sleigh
Address [2] 277728 0
Professor of Anaesthesiology
University of Auckland
22 Princes St Auckland
New Zealand 1010
Country [2] 277728 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290297 0
The Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 290297 0
The Royal Adelaide Hospital
North Terrace
Level 3 Hanson Building
Adelaide SA 5000
Ethics committee country [1] 290297 0
Australia
Date submitted for ethics approval [1] 290297 0
Approval date [1] 290297 0
24/09/2013
Ethics approval number [1] 290297 0
130714

Summary
Brief summary
The proposed study aims to evaluate Analgesia Nociception Index (ANI) titrated analgesia in patients undergoing spinal surgery. This clinical utility study is designed to investigate the effect of ANI guided fentanyl administration on post-operative events, including self-reported post-operative pain scores, analgesia administration, recovery times, and opioid-related side effects. The study will also record the incidence of unwanted intra-operative events such as tachycardia, hypertension, and the consumption of fentanyl under constant hypnotic level balanced general anaesthesia.
Trial website
None
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44942 0
Dr Andrew Wing
Address 44942 0
Department of Anaesthesia and Hyperbaric Medicine
North Terrace
The Royal Adelaide Hospital
Adelaide SA 5000
Country 44942 0
New Zealand
Phone 44942 0
+61882224000
Fax 44942 0
Email 44942 0
andrewwing1@netscape.net
Contact person for public queries
Name 44943 0
Dr Andrew Wing
Address 44943 0
Department of Anaesthesia and Hyperbaric Medicine
North Terrace
The Royal Adelaide Hospital
Adelaide SA 5000
Country 44943 0
Australia
Phone 44943 0
+61882224000
Fax 44943 0
Email 44943 0
andrewwing1@netscape.net
Contact person for scientific queries
Name 44944 0
Dr Andrew Wing
Address 44944 0
Department of Anaesthesia and Hyperbaric Medicine
North Terrace
The Royal Adelaide Hospital
Adelaide SA 5000
Country 44944 0
Australia
Phone 44944 0
+61882224000
Fax 44944 0
Email 44944 0
andrewwing1@netscape.net

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