Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000941864
Ethics application status
Approved
Date submitted
11/03/2021
Date registered
19/07/2021
Date last updated
19/07/2021
Date data sharing statement initially provided
19/07/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Methoxyflurane versus Nitrous Oxide: Which provides better pain relief in patients undergoing Trans-Vaginal Oocyte Retrieval (TVOR) with conscious sedation?
Scientific title
Methoxyflurane versus Nitrous Oxide for analgesia in patients undergoing Trans-Vaginal Oocyte Retrieval (TVOR) with conscious sedation: A randomised, non blinded control trial
Secondary ID [1] 303671 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trans vaginal oocyte retrieval 321068 0
Condition category
Condition code
Reproductive Health and Childbirth 318875 318875 0 0
Fertility including in vitro fertilisation
Anaesthesiology 318876 318876 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Assessing the effectiveness of self administered inhaled methoxyflurane 99.9% (3ml inhalation chamber device) versus Nitrous oxide 50%/ Oxygen 50% in providing procedural analgesia for patients undergoing trans vaginal oocyte retrieval. Patient will be given the allocated inhaled analgesia after identification checks have been completed, and a minimum of 1 minute prior to the start of the procedure, with inhalation ending immediately after the procedure is completed. The average time of transvaginal oocyte procedure is approximately 15-20 minutes.
Adherance to the intervention will be monitored via audit of the operation note, with study assessors asked to denote on the operation note if there have been any issues with compliance during the procedure.
Intervention code [1] 319970 0
Treatment: Drugs
Comparator / control treatment
Nitrous oxide 50%/ oxygen 50% via a demand valve mouthpiece. Patients will be allowed to self administer as much or little of the treatment as desired for the duration of the procedure.
Control group
Active

Outcomes
Primary outcome [1] 326819 0
Pain measured on 100mm VAS
Timepoint [1] 326819 0
Immediately post procedure and 15 minutes post procedure
Secondary outcome [1] 392769 0
Side effects experienced will be assessed by a study specific patient questionnaire.
Timepoint [1] 392769 0
15 minutes Post procedure
Secondary outcome [2] 392770 0
Oocyte number, which will be recorded on a study specific data collection sheet once the final count is determined by the embryologist.
Timepoint [2] 392770 0
In theatre, once the final number is determined by the embryologist, usually within 15 minutes post procedure
Secondary outcome [3] 392771 0
Fertilization rate, which will be assessed via data linkage to patients medical records
Timepoint [3] 392771 0
One week post procedure
Secondary outcome [4] 392772 0
Blastulation rate which will be assessed via data linkage to patients medical record
Timepoint [4] 392772 0
One week post procedure
Secondary outcome [5] 392773 0
Clinical pregnancy rate which will be assessed via data linkage to patients medical record
Timepoint [5] 392773 0
6 weeks post procedure
Secondary outcome [6] 392774 0
Length of procedure (from first puncture to scanner withdrawal) which will be recorded on a study specific data proforma
Timepoint [6] 392774 0
Immediately post procedure

Eligibility
Key inclusion criteria
Women undergoing Transvaginal Oocyte Retrieval (TVOR) at The Fertility Centre Liverpool (TFCL) who have consented to partake in the study.
Minimum age
18 Years
Maximum age
47 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women who have had previous adverse reaction or hypersensitivity to either agent, patients with contraindications to either medication including significant respiratory, renal or hepatic compromise, recent eye surgery using intraocular gas, patients who have taken part in the study previously and patients who request specific agents.
Of note, at TFC, as a low cost, low risk clinic our protocol dictates we do not treat patients with significant co morbidities or severe endometriosis

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)
Allocation involved contacting the holder of the computer generated allocation schedule who will be "off-site" with no clinical involvement
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculation is based on a previous study by Bhattacharya et al, 1997, in which it was reported that the mean pain level scored on a visual analogue scale of 100mm during TVOR with conscious sedation was 46.1 with a standard deviation of 21.3. Assuming a difference in the mean of each treatment of zero, based on a previous study by porter et al comparing NO2 and MFO in a trauma setting and a non inferiority limit set at 15mm on the VAS, a sample size of 43 in each arm will be required to give a test significance of 0.025 and power of 0.8.


Statistical Analysis:

Continuous variables will be analysed using the Student’s t-test. Categorical variables will be analysed using the Fisher’s exact test. Data analysis will be performed using Microsoft Excel ver 16.35. Analysis of the data will included both intention to treat and as per protocol analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
25/03/2021
Date of last participant enrolment
Anticipated
1/10/2021
Actual
Date of last data collection
Anticipated
12/11/2021
Actual
Sample size
Target
86
Accrual to date
21
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 33395 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 308090 0
Commercial sector/Industry
Name [1] 308090 0
The Fertility Centre Liverpool
Country [1] 308090 0
Australia
Primary sponsor type
Individual
Name
Dr Aine McNally Bogue
Address
c/o The Fertility Centre Liverpool
Suite 301/302
Level 3/1 Moore St
Liverpool
NSW 2710
Country
Australia
Secondary sponsor category [1] 308836 0
Individual
Name [1] 308836 0
Dr Peter Leung
Address [1] 308836 0
c/o The Fertility Centre Liverpool
Suite 301/302
Level 3/1 Moore St
Liverpool
NSW 2710
Country [1] 308836 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308076 0
IVF Australia HREC
Ethics committee address [1] 308076 0
Level 2/179 Pacific Highway
Greenwich
NSW 2065
Ethics committee country [1] 308076 0
Australia
Date submitted for ethics approval [1] 308076 0
19/03/2021
Approval date [1] 308076 0
22/03/2021
Ethics approval number [1] 308076 0

Summary
Brief summary
We hypothesise that methoxyflurane (MOF) results in non inferior pain scores on a VAS compared to nitrous oxide50%/oxygen 50% (NO2) when used by patients undergoing TVOR with conscious sedation. Both agents are proven to be effective for procedural analgesia, with good safety profiles and tolerability. While comparisons of both have been made in the settings of emergency and out of hospital medicine, no studies have assessed the two for effectiveness during TVOR. While both agents are available for use in our unit, our routine protocol used for the majority of patients calls for NO2. However benefits of MOF include portability, single use inhaler device and potentially less concern regarding occupational exposure. We therefore plan an randomised control trial to test the efficacy. In fertility, it is important to consider potential effects of any medication used on lab outcomes, which will be considered in the secondary outcomes of the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109446 0
Dr Aine McNally Bogue
Address 109446 0
c/o The Fertility Centre Liverpool
Level 3/1 Moore St
Liverpool
NSW 2170
Country 109446 0
Australia
Phone 109446 0
+61 0435325511
Fax 109446 0
Email 109446 0
[email protected]
Contact person for public queries
Name 109447 0
Dr Aine McNally Bogue
Address 109447 0
c/o The Fertility Centre Liverpool
Level 3/1 Moore St
Liverpool
NSW 2170
Country 109447 0
Australia
Phone 109447 0
+61 0435325511
Fax 109447 0
Email 109447 0
[email protected]
Contact person for scientific queries
Name 109448 0
Dr Aine McNally Bogue
Address 109448 0
c/o The Fertility Centre Liverpool
Level 3/1 Moore St
Liverpool
NSW 2170
Country 109448 0
Australia
Phone 109448 0
+61 0435325511
Fax 109448 0
Email 109448 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All the individual participant data collected, during the trial, after deidentification
When will data be available (start and end dates)?
Immediately following publication. No end date
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
To achieve aims in approved proposal
How or where can data be obtained?
Proposals to be forwarded to [email protected]. To gain access, applicants will be required to sign a data access form


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10994Study protocol  [email protected] Request to Principal Investigator
10995Clinical study report  [email protected] Request to Principal Investigator
12579Statistical analysis plan  [email protected] Request by email to Principal Investigator
12580Informed consent form  [email protected] Request by email to Principal Investigator



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.