Local oestrogen treatment in postmenopausal women undergoing pelvic organ prolapse surgery

ISRCTN	ISRCTN46661996
DOI	https://doi.org/10.1186/ISRCTN46661996
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	2014-000179-18
Protocol serial number	18990
Sponsor	Birmingham & Black Country (University Hospital Birmingham NHS Foundation Trust)
Funder	National Institute for Health Research

Submission date: 28/05/2015
Registration date: 28/05/2015
Last edited: 14/06/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Pelvic organ prolapse is the bulging or drooping of any pelvic organs (bladder, uterus, bowel) into the vagina. Prolapse is a common gynaecologic condition caused by weakening of the supporting tissues of the pelvic floor. Prolapse operations may include vaginal hysterectomy (removal of the womb vaginally) or pelvic floor repair (tightening of the front or back wall of the vagina or support the top of vagina). Hormone (oestrogen) replacement might improve the condition of the vaginal wall and help strengthen the pelvic floor, reducing complications of surgery eg water infections and improving the quality of the surgical repair. Postmenopausal women with vaginal dryness are sometimes treated with oestrogen in the form of tablets (pessaries) they insert into the vagina. However, it's not known whether vaginal application of oestrogen might reduce complications during operations for prolapse and improve long term postoperative outcomes. The aim of the LOTUS study will be to test whether treatment with vaginal oestrogen pessaries, improves prolapse related quality of life after surgery. We also want to see whether surgical complications are reduced and sexual function improved in these patients. Before starting a large study, it's important to rehearse the trial plan in a small feasibility study (treatment v no treatment), to see, for example, how many eligible women could be recruited to the study, how many would be willing to have treatment assigned at random, and how many would stick with the treatment for a specified period of time. This feasibility study will also help calculate the number of patients required for a definitive study, and the resources needed.

Who can participate?
Postmenopausal women about to undergo surgery for a pelvic organ prolapse and that have not had HRT in the last 12 months.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 (intervention) are put on a 6 week course of oestradiol (once daily for 2 weeks followed by twice weekly for four weeks) and then again twice weekly from 6-26 weeks after surgery. Those participants in group 2 (control) are not given the oestradiol treatment. All participants are then followed up 12 months after the surgery to assess their quality of life.

What are the possible benefits and risks of participating?
To date, there has been no robust data on the benefits of pre and postoperative oestrogen treatment in postmenopausal women undergoing POP surgery. A Cochrane review published in 2010 did not find any clear evidence to suggest whether oestrogens help in reducing the symptoms of POP.3 However due to frequent use, it was recommended that adequately powered RCTs with long term follow up is needed to identify benefits or risks.

Where is the study run from?
University of Birmingham Clinical Trials Unit (UK)

When is the study starting and how long is it expected to run for?
July 2015 to July 2017

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Mrs Lisa Leighton

Contact information

Mrs Lisa Leighton
Public

University of Birmingham
Birmingham Clinical Trials Unit
Division of Medical Sciences
Robert Aitken Institute
Edgbaston
Birmingham
B15 2TT
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Not specified, Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Local Oestrogen Treatment in postmenopausal women Undergoing pelvic organ prolapse Surgery (LOTUS) feasibility study
Study acronym	LOTUS
Study objectives	The aim of the LOTUS study is to establish whether treatment with vaginal oestrogen pessaries, for 6 weeks before and 52 weeks after prolapse repair surgery, improves prolapse related quality of life one year following surgery. We also want to assess whether surgical complications are reduced and sexual function improved. This will require a clinical trial of several hundred women, half of whom would receive oestrogen and half who would receive no treatment. This feasibility study is being conducted in order to help calculate the number required for a definitive study, and the resources needed.
Ethics approval(s)	West Midlands Ethics Committee, 28/04/2015, ref: 15/WM/0092
Health condition(s) or problem(s) studied	Topic: Reproductive health and childbirth; Subtopic: Reproductive Health and Childbirth (all Subtopics); Disease: Reproductive Health & Childbirth
Intervention	Intervention group (Group A): This will comprise of 6 weeks course of oestradiol 10 µg preoperatively per vaginum (once daily for 2 weeks followed by twice weekly for four weeks) and then 10µg oestradiol per vaginum twice weekly from 6-26 weeks postoperatively Follow Up Length: 12 month(s); Study Entry : Single Randomisation only
Intervention type	Biological/Vaccine
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Not provided at time of registration
Primary outcome measure(s)	Current primary outcome measure as of 04/02/2020: To obtain estimates for important aspects of the protocol to allow the development of a definitive trial Previous primary outcome measure: Improvement in prolapse related QoL at 12 months as assessed by PFDI SF20.
Key secondary outcome measure(s)	Current secondary outcome measures as of 04/02/2020: 1. Assessment of the effectiveness of patient identification and screening processes 3. Assessment of the effectiveness of the randomization process of patients 4. Evaluation of robustness of data collection processes 5. The proportion of patients followed up at six months 6. Derivation of the preliminary data from clinical outcome measures (e.g.PFDI-SF20) to inform the sample size calculation for the substantive study Previous secondary outcome measures: Improvement sexual function related quality of life (QoL) at 12 months with the use of PISQ 12 1. Reduction of intraoperative complications like tearing or button holing of the vagina and blood loss 2. Reduction in the incidence of surgical wound infection and urinary tract infection postoperatively 3. Validate Patient Global Impression of Improvement (PGI-I)19 in relation to the POP surgery, PFDI SF20 and PFIQ-7
Completion date	01/07/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	30 Years
Upper age limit	90 Years
Sex	Female
Target sample size at registration	100
Total final enrolment	100
Key inclusion criteria	1. Postmenopausal women 2. Consented to undergo surgical intervention for pelvic organ prolapse 3. Have not received HRT in the last 12 months 4. Willing to be randomised 5. Give written informed consent; Target Gender: Female; Upper Age Limit 90 years ; Lower Age Limit 30 years
Key exclusion criteria	1. Previous breast or uterine malignancy or other hormone dependent neoplasms 2. Genital bleeding of unknown origin 3. Previous thromboembolic episodes in relation to oestrogen therapy 4. Women who cannot understand speak or write in English 5. Women known to be allergic to any of the components of vaginal oestrogens 6. Two or more episodes of culture positive UTI in the last 6 months 7. Previous POP surgery 8. Voiding dysfunction(PVR>150ml) 9. Current or previous POP surgery involving mesh
Date of first enrolment	01/07/2015
Date of final enrolment	01/07/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Birmingham Women’s Hospital (Lead site)

Mindelsohn Way
Birmingham
B15 2TG
United Kingdom

Croydon University Hospital

530 London Road
Croydon
Surrey
CR7 7YE
United Kingdom

Medway Maritime Hospital

Windmill Road
Gillingham
ME7 5NY
United Kingdom

Basingstoke and North Hampshire Hospital

Aldermaston Road
Basingstoke
Hampshire
RG24 9NA
United Kingdom

Queen Alexandra Hospital

Southwick Hill Road
Portsmouth
Hampshire
PO6 3LY
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	10/09/2020	15/09/2020	Yes	No
Results article		25/08/2020	14/06/2023	Yes	No
Basic results			28/05/2020	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

14/06/2023: Publication reference added.
15/09/2020: Publication reference added.
28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
03/02/2020: The following changes have been made:
1. The primary outcome measure has been updated.
2. The secondary outcome measures have been updated.