Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001385336p
Ethics application status
Submitted, not yet approved
Date submitted
24/09/2017
Date registered
29/09/2017
Date last updated
31/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Intraoperative nitrous oxide and its role in surgery of the middle ear:
Scientific title
Intraoperative nitrous oxide and its role in surgery of the middle ear:
A randomized control trial
Secondary ID [1] 292747 0
NONE
Universal Trial Number (UTN)
U1111-1201-3482
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tympanic Membrane Retraction 304521 0
Condition category
Condition code
Ear 303858 303858 0 0
Other ear disorders
Anaesthesiology 304204 304204 0 0
Other anaesthesiology
Surgery 304205 304205 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients from both cohorts will be pre-oxygenated (100 % O2) prior to induction of anaesthesia via an open circuit for 3mins. At the discretion of the anaesthetist, patients will undergo an inhalation or intravenous induction. Inhalational induction is performed with a spontaneously breathing patient with sevoflurane in 100% oxygen. Intravenous induction is performed with propofol and preferred adjuncts. A Laryngeal mask airway or endotracheal tube is then introduced, avoiding positive pressure ventilation until the establishment of an airway device.

Once the airway has been secured, the tympanic membrane will be visualised by the surgeon, its state recorded & wide band absorbance tympanometry performed.

Following initial review, patients are randomised into 2 groups, single blinded to the Surgeon

Interventional group:
Inhale 30% O2 and 70 % Nitrous Oxide at a total flow rate of 6L for 10 mins.
The surgeon will return at 10 mins post exposure repeat tympanography and visualisation of the tympanic membrane will be performed and recorded.

Following second review, nitrous oxide will be discontinued and the anaesthetic will be conducted at the discretion of the anaesthetist. Risk of increasing rates of PONV are low due to the limited exposure to nitrous oxide 5 mins as shown by Peyton and Wu 2014.
Intervention code [1] 298987 0
Treatment: Drugs
Comparator / control treatment
Controlled Group:
Inhale 30% O2 and 70% Air at a total flow rate of 6L for 10 mins.
The surgeon will return at 10 mins post exposure repeat tympanography and visualisation of the tympanic membrane will be performed and recorded.
Following second review, nitrous oxide will be discontinued and the anaesthetic will be conducted at the discretion of the anaesthetist.
Control group
Placebo

Outcomes
Primary outcome [1] 303214 0
Tympanic Membrane Retraction vs No Tympanic Membrane Retraction
- This will be assessed under microscopy by the consultant surgeon
- The tympanic membrane will be reported as retracted, and graded according to Sade 1-5.
Timepoint [1] 303214 0
Following intubation the consultant will review the tympanic membrane this will be considered 0 mins (prior to intervention). 10 minutes post conduction of intervention the surgeon will again eyeball the tympanic membrane.
Secondary outcome [1] 338259 0
Tympanometry will be conducted using a portable instrument, results will be graphed accordingly admittance over air pressure.
Timepoint [1] 338259 0
Following intubation the consultant will review the tympanic membrane, after this tympanometry will be performed this will be considered 0 mins (prior to intervention). 10 minutes post conduction of intervention the surgeon will again eyeball the tympanic membrane and tympanometry will again be repeated.
Secondary outcome [2] 339044 0
Surgeon Satisfaction:
- Three-point linkert scale will be used
Timepoint [2] 339044 0
Post-operatively
Secondary outcome [3] 339045 0
Acute Post-operative complications:
- Nausea as reported by the patient Y/N
- Vomiting Y/N
- Antiemetic use - all anti-emetics used post-operatively will be documented.
Timepoint [3] 339045 0
within 24 hours post-operatively
Secondary outcome [4] 339046 0
Post-operative outcomes:
Tympanometry will be conducted using a portable instrument, results will be graphed accordingly admittance over air pressure.
Timepoint [4] 339046 0
3 months post surgery

Eligibility
Key inclusion criteria
Patients aged 2-80 with Sade stage 2 tympanic membrane retraction or higher undergoing surgery to the outer or middle ear at the Townsville Hospital or Mater Health Service North Queensland.
Minimum age
2 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any condition where there is potential pathological gas fluid space - post-op recent bowel surgery; pneumoperitoneum, pneumocranium.

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)
Using computer generated sealed envelopes patients were allocated to one of two treatment groups; those receiving nitrous oxide as part of operative procedure versus those receiving a standardized anaesthetic regime with equal persons to both cohorts.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised 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
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
• Sample Size: Sample size was based upon findings from Koivenen et al. 1996. Thirty patients are required to have a 95% chance of detecting, as significant at the 5% level, an increase in the primary outcome measure from 25% in the control group to 90% in the experimental group with a 10% adjustment for non-compliance.
• Data Analysis: Data will be collected using SPSS database. Pearson’s chi-squared test for independence will be used to assess the relationship between Nitrous versus the control group on normalization of the tympanic membrane. Analysis of covariance will be used to assess if there is a significant difference in the middle ear pressure in participants receiving Nitrous Oxide versus the control group while controlling for their pre-intervention scores.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2018
Actual
Date of last participant enrolment
Anticipated
1/09/2019
Actual
Date of last data collection
Anticipated
1/12/2019
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 8899 0
The Townsville Hospital - Douglas
Recruitment hospital [2] 9099 0
Mater Hospital Pimlico - Pimlico
Recruitment postcode(s) [1] 17598 0
4810 - Pimlico
Recruitment postcode(s) [2] 17145 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 297385 0
Hospital
Name [1] 297385 0
The Townsville Hospital
Country [1] 297385 0
Australia
Primary sponsor type
Hospital
Name
The Townsville Hospital
Address
The Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville QLD 4814
Country
Australia
Secondary sponsor category [1] 296369 0
None
Name [1] 296369 0
Address [1] 296369 0
Country [1] 296369 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 298485 0
The Townsville Health Service District Institutional Ethics Committee
Ethics committee address [1] 298485 0
The Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville QLD 4814
Ethics committee country [1] 298485 0
Australia
Date submitted for ethics approval [1] 298485 0
25/09/2017
Approval date [1] 298485 0
Ethics approval number [1] 298485 0

Summary
Brief summary
Tympanic membrane retraction can lead to increased technical difficulties for surgeons when conducting tympanoplastic procedures. Nitrous Oxide is a commonly used inhaled anaesthetic agent that has a solubility 35 times higher than Nitrogen. Its diffusion into the middle ear has been well reported and the effects on middle ear pressure and effusions have previously been investigated. Currently, at the discretion of the anesthetist and surgeon the use of Nitrous Oxide as part of anesthetic prior to surgery to the middle ear is conducted at our hospital. It has been noted that in patients with a retraction, normalization of the tympanic membrane can occur thereby allowing for ease of surgery. This study aims to assess the effect of Nitrous Oxide on retracted tympanic membranes, in a controlled manner to see if this practice should be implemented as a standard of care. It is hypothesized that the use of Nitrous Oxide at the time of induction on patients with tympanic membrane retraction will result in normalization of positioning of the membrane thereby allowing for ease of surgery.

A multicenter randomized prospective control trial will be conducted at the Townsville Hospital and the Mater Health Service North Queensland. All patients undergoing middle ear surgery with a retracted tympanic membrane graded Sade 2 or higher will be assessed for suitability for participation. Patients will be randomized via random number generator into two groups of either 30% Oxygen and 70 % Nitrous Oxide vs 30% Oxygen and Air. At time of surgery following the insertion of airway device, the tympanic membrane will be visualized by the surgeon, its state recorded and tympanography will be performed. Single blinded to the Surgeon; who will leave the operating room to prepare for surgery, the maintenance gases will be commenced at 6L/min for 10 minutes. Following cessation, the surgeon will return and again visualize the tympanic membrane and repeat tympanography will be performed allowing for comparison. The operation will then commence. Following the surgery the surgeon will document his personal experience or ease of surgery using a standardized system. Postoperative nausea or vomiting will be documented as well as use of antiemetic’s. Patients will be followed up at 3 months as per our hospitals standard procedures and any complications will be noted.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77234 0
Dr Jemma Porrett
Address 77234 0
The Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville QLD 4814
Country 77234 0
Australia
Phone 77234 0
+61, 7, 44331111
Fax 77234 0
Email 77234 0
jemma.porrett@health.qld.gov.au
Contact person for public queries
Name 77235 0
Dr Jemma Porrett
Address 77235 0
The Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville QLD 4814
Country 77235 0
Australia
Phone 77235 0
+61, 7, 44331111
Fax 77235 0
Email 77235 0
jemma.porrett@health.qld.gov.au
Contact person for scientific queries
Name 77236 0
Dr Jemma Porrett
Address 77236 0
The Townsville Hospital
100 Angus Smith Drive
Douglas, Townsville QLD 4814
Country 77236 0
Australia
Phone 77236 0
+61, 7, 44331111
Fax 77236 0
Email 77236 0
jemma.porrett@health.qld.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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