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Trial registered on ANZCTR


Registration number
ACTRN12624000927527
Ethics application status
Approved
Date submitted
10/07/2024
Date registered
1/08/2024
Date last updated
1/08/2024
Date data sharing statement initially provided
1/08/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
ENDOmetriosis appearance with hormonal COntraceptives at LaparOscopy: a pRospective cohort study (ENDO-COLOR Trial)
Scientific title
ENDOmetriosis appearance with hormonal COntraceptives at LaparOscopy: a pRospective cohort study (ENDO-COLOR Trial) in 18-60 year old women
Secondary ID [1] 312489 0
Nil
Universal Trial Number (UTN)
Trial acronym
ENDO-COLOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 334347 0
Condition category
Condition code
Reproductive Health and Childbirth 330995 330995 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All participants planned for laparoscopic excision of endometriosis who meet inclusion and exclusion criteria will be divided into two groups; hormonal users (HUs) and non-users (NUs).

Hormone use will be defined as women using any of the following within 30 days of surgery; combined hormonal contraceptive pill, progesterone only contraceptive pill, contraceptive implant (Implanon NXT), levonorgestrel releasing intrauterine device (LNG-IUD) or a progesterone depot contraceptive injection within 90 days of surgery. A preoperative participant questionnaire will capture participant reported hormone use. All other women will be defined as non-users.

Participants will be recruited pre-operatively and followed up for 6 months following laparoscopic excision of endometriosis until completion of the 6 month postoperative questionnaire.

Demands on participants
Participants of this study will be asked to consent to enrolment, complete a preoperative and postoperative questionnaire, and to have intraoperative medical data prospectively collected by research staff.

The participant questionnaires include questions about:
- Hormonal medication use
- Demographics
- Pelvic pain
- Past medical history
- EHP-30 to assess quality of life
These will be assessed with an online questionnaire administered through RedCap. We estimate this to take participants 20-30 minutes to complete.
Intervention code [1] 329006 0
Diagnosis / Prognosis
Comparator / control treatment
All women not meeting the aforementioned criteria as hormonal contraceptive users will be defined as non-users.
Control group
Active

Outcomes
Primary outcome [1] 338763 0
Colour of endometriosis lesions at laparoscopy, presented as the frequency and percentage of participants with black lesions.
Timepoint [1] 338763 0
At laparoscopy
Secondary outcome [1] 437364 0
Percentage and frequency of stage of endometriosis by r-ASRM stage.
Timepoint [1] 437364 0
At laparoscopy
Secondary outcome [2] 437365 0
Colour of endometriosis lesions, presented as frequency and percentage of participants with each of the four lesion colours in the hormonal medication user (HU) and non-hormone user (NU) groups.
Timepoint [2] 437365 0
At laparoscopy
Secondary outcome [3] 437366 0
Histopathological diagnosis of endometriosis presented as percentage and frequency.
Timepoint [3] 437366 0
Histopathology review questionnaire, completed 1-2 weeks postoperatively.
Secondary outcome [4] 437367 0
Percentage and frequency of stage of endometriosis by deep infiltrating endometriosis (DIE) stage.
Timepoint [4] 437367 0
At laparoscopy
Secondary outcome [5] 437368 0
Mean difference in pain scores on passing urine.
Timepoint [5] 437368 0
Preoperative questionnaire, 6 weeks questionnaire
Secondary outcome [6] 437369 0
Mean difference in pelvic pain scores.
Timepoint [6] 437369 0
Preoperative questionnaire, 6 week postoperative questionnaire
Secondary outcome [7] 437370 0
Mean difference in EHP-30 score.
Timepoint [7] 437370 0
Preoperative participant questionnaire, 6 week postoperative participant questionnaire.
Secondary outcome [8] 437371 0
Percentage and frequency of haemosiderin-laden macrophages on histopathology reports.
Timepoint [8] 437371 0
Histopathology review questionnaire, completed 1-2 weeks postoperatively.
Secondary outcome [9] 437685 0
Mean difference in pain scores on opening bowels
Timepoint [9] 437685 0
Preoperative questionnaire, 6 weeks questionnaire
Secondary outcome [10] 437687 0
Mean difference in pain scores with sexual intercourse
Timepoint [10] 437687 0
Preoperative questionnaire, 6 weeks questionnaire
Secondary outcome [11] 437688 0
Mean difference in period pain scores.
Timepoint [11] 437688 0
Preoperative questionnaire, 6 weeks questionnaire

Eligibility
Key inclusion criteria
Women aged between 18-60 years of age undergoing laparoscopy for diagnosis and excision of suspected endometriosis.
Women with the capacity to give written consent freely
Minimum age
18 Years
Maximum age
60 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous surgical excision of endometriosis
- Use of GNRH analogues, danazol, selective oestrogen receptor modulators in the 6 months prior to laparoscopy
- Patients unsure of their current or recent hormonal contraceptive use
- Pregnant women

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Primary outcome
The primary outcome, colour of endometriosis lesions, will be presented in a contingency table as frequency and percentage of black lesions in the HCU compared to the NU group. As we expect the event rate of black lesions to be greater than 10%, relative risk will be used to present the estimate of effect. Their association will be analysed with a Chi-squared test to test for statistical significance, charting frequencies in a 2 x 2 contingency table.

Secondary outcomes
Lesion colour will also be compared between the HCU and NU groups in a contingency table with lesion colour (white, black, red or mixed) as the dependent variable.
Categorical data will be presented as frequencies and percentages. Correlations will be analysed using a chi-squared test or Fischer’s exact test for variables with expected frequencies of less than 5 in a single cell of a resultant contingency table.
Mean difference in pelvic pain, pain in other domains and EHP-30 scores will be assessed with a dependent-samples t-test or Wilcoxon’s signed-rank test (depending on normality of data) by comparing preoperative scores with 6 week postoperative scores between the HCU and NU groups.
Estimates of effect will be presented as relative risk for categorical variables or mean difference for continuous variables, with accompanying 95% confidence intervals. A p value of < 0.05 will be considered as statistically significant.

Given the relatively small sample size we will not undertake regression analyses.

Every attempt will be made to collect full follow-up data on all women (unless a woman withdraws consent for follow-up data collection). It is thus anticipated that missing data will be minimal. Women with missing primary outcome data will not be included in the primary analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
25/04/2022
Date of last participant enrolment
Anticipated
31/07/2024
Actual
Date of last data collection
Anticipated
11/09/2024
Actual
Sample size
Target
106
Accrual to date
92
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 316909 0
Government body
Name [1] 316909 0
South Eastern Sydney Local Health District
Country [1] 316909 0
Australia
Funding source category [2] 316990 0
Other Collaborative groups
Name [2] 316990 0
Sydney Minimally Invasive Gynaecological Research Group (SMIGs-RG)
Country [2] 316990 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Sydney Minimally Invasive Gynaecology Research Group
Address
Country
Australia
Secondary sponsor category [1] 319158 0
None
Name [1] 319158 0
Address [1] 319158 0
Country [1] 319158 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315667 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 315667 0
https://www.seslhd.health.nsw.gov.au/services-clinics/directory/research-home/ethics
Ethics committee country [1] 315667 0
Australia
Date submitted for ethics approval [1] 315667 0
10/02/2021
Approval date [1] 315667 0
30/03/2021
Ethics approval number [1] 315667 0
2021/ETH00246

Summary
Brief summary
Endometriosis is a common condition where deposits of endometrium are found outside of the uterus, typically in other pelvic organs. Endometriosis has a significant impact on quality of life, pain, sexual function and fertility for women who suffer from it. Laparoscopy (keyhole surgery) plays a crucial role in allowing diagnosis of endometriosis and therapeutic benefit in excision of disease.

While black pigmented “powder-burn” endometriosis lesions are classically described, other non-pigmented red or white lesions are common. Causes of variation in lesion appearance have not been well explored and are not well understood. Past studies have found high concentrations of iron deposition in endometriotic lesions compared to normal peritoneum. This iron deposition is due to cyclical bleeding into ectopic endometrial implants, due to falling progesterone levels at the end of the menstrual cycle. Macrophages (a type of white blood cell) initially phagocytose (ingest) haemoglobin, which is broken down into iron and then converted to hemosiderin, which is typically black or pigmented. These hemosiderin-laden macrophages are one of the diagnostic features of endometriosis on histopathology.

Hormonal contraceptive medications are commonly used to treat endometriosis. They prevent pain through a range of mechanisms but crucially by suppressing a woman's production of sex hormones, thereby preventing cyclical bleeding from endometriosis deposits and an associated inflammatory response. We hypothesize that the use of hormonal contraceptives would inhibit proliferation of endometrial tissue and subsequent bleeding from endometriotic deposits. This effect of hormonal contraceptives would also reduce the number of haemosiderin-laden macrophages in endometriosis lesions, thereby reducing their black appearance.

No previous studies have investigated the factors that influence lesion appearance at laparoscopy. As such reasons for variation in lesions and the effect of hormonal contraceptives on lesion appearance is unknown.

Fewer black lesions may lead to more missed lesions at laparoscopy, with more lesions appearing red or white. It may also lead to atrophy of endometrial glandular tissue leading to difficulty in diagnosing endometriosis on histopathology. If this effect exists, awareness of it by surgeons would be useful and may facilitate complete excision of endometriosis at initial laparoscopy. This has been shown to improve pain and quality of life compared to incomplete excision.

Our primary objective is to assess whether the use of hormonal contraceptives effects the colour of endometriosis lesions at laparoscopy. Our secondary objective is to assess if hormonal contraceptives effect the histological appearance of endometriosis lesions and if this this is related to their colour.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135438 0
Dr William Stobie
Address 135438 0
Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086
Country 135438 0
Australia
Phone 135438 0
+61 425891556
Fax 135438 0
Email 135438 0
[email protected]
Contact person for public queries
Name 135439 0
William Stobie
Address 135439 0
Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086
Country 135439 0
Australia
Phone 135439 0
+61 425891556
Fax 135439 0
Email 135439 0
[email protected]
Contact person for scientific queries
Name 135440 0
William Stobie
Address 135440 0
Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086
Country 135440 0
Australia
Phone 135440 0
+61 425891556
Fax 135440 0
Email 135440 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We plan to publish data and findings in full in a relevant peer-reviewed medical journal on completion of the trial. At present there is no plan, nor do we have a platform to publish individual participant data, but this may be shared for the purposes of future systematic reviews on request.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23976Ethical approval    388095-(Uploaded-10-07-2024-05-52-45)-383564-(Uploaded-02-04-2022-14-57-40)-Study-related document.pdf



Results publications and other study-related documents

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