ANZCTR - Registration

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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]

Nil

Universal Trial Number (UTN)

Trial acronym

ENDO-COLOR

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Endometriosis

Condition category

Condition code

Reproductive Health and Childbirth

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]

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]

Colour of endometriosis lesions at laparoscopy, presented as the frequency and percentage of participants with black lesions.

Timepoint [1]

At laparoscopy

Secondary outcome [1]

Percentage and frequency of stage of endometriosis by r-ASRM stage.

Timepoint [1]

At laparoscopy

Secondary outcome [2]

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]

At laparoscopy

Secondary outcome [3]

Histopathological diagnosis of endometriosis presented as percentage and frequency.

Timepoint [3]

Histopathology review questionnaire, completed 1-2 weeks postoperatively.

Secondary outcome [4]

Percentage and frequency of stage of endometriosis by deep infiltrating endometriosis (DIE) stage.

Timepoint [4]

At laparoscopy

Secondary outcome [5]

Mean difference in pain scores on passing urine.

Timepoint [5]

Preoperative questionnaire, 6 weeks questionnaire

Secondary outcome [6]

Mean difference in pelvic pain scores.

Timepoint [6]

Preoperative questionnaire, 6 week postoperative questionnaire

Secondary outcome [7]

Mean difference in EHP-30 score.

Timepoint [7]

Preoperative participant questionnaire, 6 week postoperative participant questionnaire.

Secondary outcome [8]

Percentage and frequency of haemosiderin-laden macrophages on histopathology reports.

Timepoint [8]

Histopathology review questionnaire, completed 1-2 weeks postoperatively.

Secondary outcome [9]

Mean difference in pain scores on opening bowels

Timepoint [9]

Preoperative questionnaire, 6 weeks questionnaire

Secondary outcome [10]

Mean difference in pain scores with sexual intercourse

Timepoint [10]

Preoperative questionnaire, 6 weeks questionnaire

Secondary outcome [11]

Mean difference in period pain scores.

Timepoint [11]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

NSW

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

South Eastern Sydney Local Health District

Address [1]

Country [1]

Australia

Funding source category [2]

Other Collaborative groups

Name [2]

Sydney Minimally Invasive Gynaecological Research Group (SMIGs-RG)

Address [2]

Country [2]

Australia

Primary sponsor type

Other Collaborative groups

Name

Sydney Minimally Invasive Gynaecology Research Group

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Eastern Sydney Local Health District HREC

Ethics committee address [1]

https://www.seslhd.health.nsw.gov.au/services-clinics/directory/research-home/ethics

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/02/2021

Approval date [1]

30/03/2021

Ethics approval number [1]

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

Dr William Stobie

Address

Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086

Country

Australia

Phone

+61 425891556

Fax

wmstobie@gmail.com

Contact person for public queries

Name

William Stobie

Address

Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086

Country

Australia

Phone

+61 425891556

Fax

wmstobie@gmail.com

Contact person for scientific queries

Name

William Stobie

Address

Northern Beaches Hospital, 105 Frenchs Forest Rd W, Frenchs Forest NSW 2086

Country

Australia

Phone

+61 425891556

Fax

wmstobie@gmail.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
23976	Ethical 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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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