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Trial registered on ANZCTR


Registration number
ACTRN12615000828527
Ethics application status
Approved
Date submitted
9/07/2015
Date registered
11/08/2015
Date last updated
21/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Hysteroscopic Morcellator versus Electrosurgical resection for Submucosal Leiomyoma
Scientific title
A Randomised Controlled, Cost Minimisation Trial of Hysteroscopic Morcellation versus Electrosurgical Resection for Submucosal Leiomyomas in Women with Abnormal Uterine Bleeding Type Leiomyoma (AUB-L)
Secondary ID [1] 287067 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Submucosal Leiomyoma 295565 0
Condition category
Condition code
Reproductive Health and Childbirth 295833 295833 0 0
Other reproductive health and childbirth disorders
Surgery 295983 295983 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Hysteroscopic morcellator for removal of submucosal leiomyoma

A rigid tube 7mm in diameter is introduced into the uterine cavity. It has a light source, camera head, and inflow and outflow valves, and channel to allow the morcellator to be inserted. The hysteroscopic morecellator is a rigid tube with a oscillating blade contained within a metal sheath. It works by sucking material into the open tube and the blade cuts the material and sucks in one movement.

The hysteroscopic morcellator to be used is the Myosure (Registered trademark)

Distension medium is normal saline. The maximum amount allowed to be absorbed by the patient is 2500ml. This will be controlled by aquasence (registered trademark) that will measure the inflow and outflow of normal saline

The procedure will be performed by a certified gynaecologist or trainee under their supervision. All gynaecologists involved are experienced in the use of this device.

The procedure will be undertaken under general anaesthetic

The duration of the procedure will depend on the type, number, and location of leiomyoma. It is expected the average resection time will be 24 minutes.

Intervention code [1] 292299 0
Treatment: Devices
Comparator / control treatment
Monopolar electrosurgical hysteroscopic resection

The resectoscope is a rigid tube 10mm in diameter and it is introduced into the uterine cavity. It has a light source, camera head, and inflow and outflow valves, and an operating channel to allow the instruments to be inserted into the uterus to undertake resection. The monopolar loop is the instrument being inserted into the operating channel. Using electrosurgery, the monopolar loop directly cuts into the leiomyoma and removes it in pieces under direct vision.

Distension medium is glyciene. The maximum amount allowed to be absorbed by the patient is 1000ml. This will be controlled by aquasence (registered trademark) that will measure the inflow and outflow of glyciene

The procedure will be performed by a certified gynaecologist or trainee under their supervision. All gynaecologists involved are experienced in the use of this device.

The procedure will be undertaken under general anaesthetic

The duration of the procedure will depend on the type, number, and location of leiomyoma. It is expected the average resection time will be 30 minutes.

Control group
Active

Outcomes
Primary outcome [1] 295521 0
The primary outcome of this trial is cost effectiveness. As the 2 procedures are identical in their initial approach, the 2 determining factors are cost of the device, and the operating theatre costs. To identify the cost difference, the resection time of the leiomyoma is of primary importance.
Timepoint [1] 295521 0
From insertion of the hysteroscope to removal of instrumentation
Secondary outcome [1] 315767 0
Fluid deficit
This is measured by aquasence (Registered trademark). There are strict policies on the maximum fluid (either normal saline or glycine) that can be absorbed by the patient before the become at risk for electrolyte disturbances
Timepoint [1] 315767 0
At the end of the operation
Secondary outcome [2] 315768 0
Completeness of resection

This will be estimated by the surgeon at the time of operation. Where resection is <90%, the surgeon will be asked to identify the cause of this.
Timepoint [2] 315768 0
1. At the end of the operation

2. The impact of the completness of resection will be compared against a patients symptoms at 6 weeks and 6 months post operatively
Secondary outcome [3] 316125 0
Number of adverse events, inlcuding minor and major events.

Minor complications that may occur with resection of a submucosal leiomyoma include:
1. General anaesthesia reaction
2. Nerve injury
3. Trauma to the vascular system < 500 mL blood loss but not requiring blood transfusion e.g. haematoma formation.
4. Unintentional trauma to the genital system e.g. Perforated uterus
5. Glycine Deficit > 1000ml or Normal Saline > 2500ml with resulting electrolyte disturbance

Major complications that may occur with resection of a submucosal leiomyoma include:
1. Unintentional trauma to bladder, ureter, intestinal tract, fallopian tube, and ovary
2. Trauma to the vascular system > 500mL requiring blood transfusion
3. Unplanned removal of organ e.g. ovary, fallopian tube, uterus, appendix
Timepoint [3] 316125 0
The Timepoints to identify adverse events include:
1. At the time of surgery
2. At 6 week check up
3. At 6 month check up

There are also systems in place to identify patients who have attended a health care setting for possible complications in between these times.

Eligibility
Key inclusion criteria
Women undergoing surgical resection of submucosal leiomyoma
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Pregnant women.
2. Immunocompromised women.
3. Current involvement in any other research project.
4. Women who are suspected to have a gynaecological malignancy

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)
Point of entry into the study will occur during clinical consultation where hysteroscopy and removal or a leiomyoma is deemed necessary by the clinician. There is no benefit to the clinician to enrol women without a leiomyoma. As enrolment will occur after outpatient consultation, it is expected that women would present with symptoms relating to the leiomyoma. If an incidental leiomyoma is identified sonographically in the absence of symptoms, this woman would not be eligible for inclusion in the study since determination of outcomes is not possible in this clinical setting. Following a decision to list a woman for a hysteroscopy and removal of a symptomatic leiomyoma, all women will be offered participation in the study subject should they meet the inclusion and exclusion criteria.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
After women have been enrolled into the study and completed their pre-operative documentation they will be randomised to treatment allocation. Randomisation of women into treatment groups will occur via phone to an automated service that uses simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
From an RCT of hysteroscopic resection examining clinical outcomes, resection time was reported with a mean of 49.4 minutes and standard deviation of 29.4 minutes. The surgeons in this RCT were all experienced consultants and other studies have reported a wide range of mean monopolar hysteroscopic resection times for submucosal leiomyomas ranging from 23.2min (SD 8.2min) to 42.2min (SD 2.5min). When these studies are pooled, the mean hysteroscopic resection time is 30.6min (Variance 192.15, SD 13.9min).
Accepting an estimated mean monopolar resection time of 30.6min, a sample size of 81 women in each group would be needed to detect a conservative 20% decrease in resection time with 80% power at the 5% significance level.
Analysis of all primary and secondary outcome measures will be on an intention-to-treat basis. Demographic data will be compared using appropriate parametric and non-parametric statistical tests following the assessment of the distribution of the data by the Kolgarov-Smirnov method.
An economic evaluation will be conducted to determine the relative costs and benefits of hysteroscopic morcellation versus electrosurgical resection. Medical costs will be estimated using the relevant MBS fees to each occasion of service; in-hospital treatment costs for the original procedure (hysteroscopic morcellator versus electrosurgical resection) and any repeat procedures carried out during the follow-up period will be estimated using standard hospital cost weights; and any pharmaceutical costs (for example for the treatment of fluid overload) will be estimated based on standard prescription protocols and pharmaceutical product prices. Out of pocket costs will be measured as the difference between average fees paid by women for medical practitioner services, hospital services, pharmaceuticals and alternative therapies and any health insurance rebates (including Medicare) available to women for those services. Costs directly associated with the trial (i.e. procedure and pharmaceutical costs) will be available from the treatment protocols and women’s medical records. The services of a health economist have been retained for the purposes of consultation at the time of initiation of this protocol and for analyses of data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/01/2016
Actual
26/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
162
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4026 0
Royal Hospital for Women - Randwick
Recruitment hospital [2] 4027 0
Prince of Wales Private Hospital - Randwick
Recruitment hospital [3] 4028 0
Mater Sydney - North Sydney

Funding & Sponsors
Funding source category [1] 291625 0
University
Name [1] 291625 0
University of New South Wales
Country [1] 291625 0
Australia
Primary sponsor type
Other
Name
Gynaecology Research and Clinical Evaluation Group
Address
School of Women's and Children's Health
Level 1, Barker St
Randwick, NSW, 2031
Country
Australia
Secondary sponsor category [1] 290297 0
Hospital
Name [1] 290297 0
Royal Hospital for Women
Address [1] 290297 0
Barker St
Randwick, NSW 2031
Country [1] 290297 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293156 0
South Eastern Sydney Local Health District (EC00134)
Ethics committee address [1] 293156 0
Ethics committee country [1] 293156 0
Australia
Date submitted for ethics approval [1] 293156 0
31/07/2015
Approval date [1] 293156 0
30/05/2016
Ethics approval number [1] 293156 0
15/169

Summary
Brief summary
This study will compare the use of a mechanical hysteroscopic morcellator to monopolar electrosurgical
hysteroscopic resection to remove submucosal fibroid in symptomatic women. We hypothesize the hysteroscopic
morcellator may reduce intraoperative time and allow additional procedures to be performed in a single operating
list. The primary outcome of this study is to determine the difference if there is a difference in cost between two devices used to to resect the leiomyomas. As the operating time will is the most likely to have an impact on this, the time to resect intrauterine pathology between these two different instruments, from insertion of the hysteroscope to removal of instrumentation will form part of this primary outcome. Secondary
outcomes include: Fluid deficit, Completeness of resection, and adverse events

This is a prospective, randomised, single blinded
study, with a minimum of 162 patients to be enrolled over a 1year recruitment period. All cases must satisfy the inclusion/exclusion criteria and will be followed for 6 months after
surgery.

Following decision to list a woman for a hysteroscopy and resection of fibroid, women will be considered for the
study and offered participation. Women who qualify will be randomised to one of two groups: Hysteroscopic
morcellator (Myosure, Registered trademark) with normal saline distension medium or monopolar electrosurgical hysteroscopic resector
with a glycine distension medium.

To ensure concealment, randomisation of women into treatment groups will occur via phone to an automated
randomisation service. At the time of surgery, a diagnostic hysteroscopy will first be performed to confirm
requirement for resection of a fibroid. Those that do not require resection will continue to have outcome data
collected during the operation and followup
but will not be included in analysis.

Data collection will occur at: recruitment, on the day of admission for surgery and intraoperatively, postoperative
review at 6 weeks after index surgery, and postoperative
review at 6 months after index surgery. An economic
evaluation will be conducted to determine the relative costs and benefits of hysteroscopic morcellation versus
electrosurgical resection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58694 0
A/Prof Jason Abbott
Address 58694 0
School of Women's and Children's Health
Level 1, Barker St
Randwick, NSW, 2031
Country 58694 0
Australia
Phone 58694 0
+61 2 9382 6733
Fax 58694 0
Email 58694 0
[email protected]
Contact person for public queries
Name 58695 0
Dr Aaron Budden
Address 58695 0
School of Women's and Children's Health
Level 1, Barker St
Randwick, NSW, 2031
Country 58695 0
Australia
Phone 58695 0
+61 2 9382 6733
Fax 58695 0
Email 58695 0
[email protected]
Contact person for scientific queries
Name 58696 0
Dr Aaron Budden
Address 58696 0
School of Women's and Children's Health
Level 1, Barker St
Randwick, NSW, 2031
Country 58696 0
Australia
Phone 58696 0
+61 2 9382 6733
Fax 58696 0
Email 58696 0
[email protected]

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

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

Documents added automatically
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