DEsogestrel for Bleeding on the Implant (DEBI)
| ISRCTN | ISRCTN10116165 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10116165 |
| IRAS number | 1007190 |
| Secondary identifying numbers | 24045 |
- Submission date
- 27/03/2025
- Registration date
- 28/05/2025
- Last edited
- 03/07/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English summary of protocol
Background and study aims
The contraceptive implant (68mg etonogestrel) is a hormone-containing rod that is placed under the skin of the arm and is more than 99% effective at preventing pregnancy. Unfortunately, 24% of users have the implant removed early due to frustrating and unpredictable changes in their periods. Bad experiences with the implant deter people from using other effective contraceptive methods and may increase the risk of unintended pregnancy.
The current first-line treatment that is recommended is to take the combined oral contraceptive pill (COCP). This research aims to see whether desogestrel is as good as COCP in reducing problematic bleeding while using the implant. Desogestrel is slightly safer and cheaper than the combined pill, can be used in people who cannot take the combined pill and can be bought without a prescription. Using desogestrel means that people are only exposed to one type of hormone rather than two in the combined oral contraceptive pill. People taking the combined pill require annual blood pressure and weight monitoring, which is not required with desogestrel. If desogestrel is found to be as good as the combined pill, it will mean a safer, cheaper, more accessible treatment for problematic bleeding on the implant.
Who can participate?
The trial will recruit 690 menstruating people aged 16-45 with self-reported problem bleeding whilst using the etonogestrel implant. Problem bleeding is defined as bleeding of any type (e.g. spotting/heavy) considered problematic by the person. They must be willing to complete a daily bleeding diary for the trial duration.
What does the study involve?
The research aims to see whether desogestrel is as good as the combined oral contraceptive pill in settling problem bleeding during 90 days for people with problem bleeding whilst using the etonogestrel implant. Resolution of problem bleeding is defined as people self-reporting a significant improvement in the bleeding pattern during the 90-day reference period. Daily bleeding diary and adherence questions have been combined to reduce the time burden on participants. There are no follow-up visits required in addition to usual care, and follow-up questionnaires have been designed to only ask what is needed to answer the trial outcomes.
What are the possible benefits and risks of participating?
Both desogestrel and the COCP have marketing authorisation in the UK for oral contraception, but for this trial they will be used outside of their marketed purpose. Desogestrel is an unevidenced treatment used in clinical practice. Risks related to trial treatment (common side effects) are described in the patient information sheet and medicine information leaflet (for both COCP and desogestrel), and they will be advised by the clinician on treatment in accordance with their local policies. Full details of side effects are available in the individual SmPC patient information sheet. Safety monitoring will be conducted as per the Monitoring Plan.
Where is the study run from?
University of Nottingham, UK
When is the study starting and how long is it expected to run for?
April 2024 to July 2027
Who is funding the study?
NIHR Health Technology Assessment Programme, HTA
Who is the main contact?
debi@nottingham.ac.uk
Contact information
Scientific, Principal Investigator
University of Nottingham
Academic O&G Corridor
D Floor
East Block Queen's Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
| Phone | +44 (0)7812276028 |
|---|---|
| Kate.walker@nottingham.ac.uk |
Scientific
Community Sexual and Reproductive Health Consultant
Nottingham University Hospitals NUH Trust
Integrated Sexual Health Service, Nottingham City Hospital, GU Medicine Building, Gate 2, Hucknall Road
Nottingham
NG5 1PB
United Kingdom
| Phone | +44 (0)115 969 1169 ext. 73696 |
|---|---|
| hlathamcork@nhs.net |
Public
University of Nottingham
Nottingham Clinical Trials Unit
Applied Health Research Building
Nottingham
NG7 2RD
United Kingdom
| DEBI@nottingham.ac.uk |
Study information
| Study design | Multicentre clinician- and participant-blinded randomized non-inferiority trial with economic evaluation |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Efficacy |
| Scientific title | Clinical and cost-effectiveness of desogestrel versus the combined oral contraceptive pill for problematic bleeding on the etonogestrel implant: DEBI trial |
| Study acronym | DEBI |
| Study objectives | To establish whether desogestrel is non-inferior to the combined oral contraceptive pill (COCP) in settling problem bleeding during a 90-day reference period for people with problem bleeding whilst using the etonogestrel implant. Resolution of problem bleeding is defined as people self-reporting significant improvement in the bleeding pattern during the 90-day reference period. To establish if the proportion of participants reporting problem bleeding is not worse in participants treated with desogestrel compared to COCP. To determine the effect of desogestrel compared with COCP on total number of non-bleeding, spotting and bleeding days during the 90-day treatment period. To determine the effect of desogestrel compared with COCP on the number and duration of bleeding episodes (one or more consecutive days of bleeding, bounded by bleed-free days) within the 90 days . To determine the effect of desogestrel compared with COCP on the time to the longest consecutive non-bleeding days. To determine the acceptability with trial treatment. To establish participant adherence to treatment. To determine the effect of desogestrel and COCP on participant Quality of life. To determine the cost of treating implant user problem bleeding with desogestrel or the COCP. To determine the proportion of participants who intend to continue their allocated treatment. |
| Ethics approval(s) |
Approved 07/05/2025, North West - Greater Manchester Central Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8084; gmcentral.rec@hra.nhs.uk), ref: 25/NW/0110 |
| Health condition(s) or problem(s) studied | Self-reported problem bleeding on the contraceptive implant |
| Intervention | Intervention: desogestrel 75 micrograms, once daily by mouth. Active comparator: 30 microgram ethinylestradiol and 150 microgram levonorgestrel COCP, 1 tablet daily by mouth (without a hormone-free interval). Both COCP and desogestrel tablets will be similar oval, unmarked, white tablets to mask the allocation. This is a phase IV, multicentre, clinician and participant-blinded, randomised non-inferiority trial, with economic evaluation. Equal allocation (1:1) to receive either desogestrel (intervention) or COCP (usual care). Recruitment of 690 participants is required to achieve 90% power and conclude non-inferiority with respect to the resolution of problem bleeding. Randomisation will be provided by REDCap, a secure online randomisation system at the NCTU. Unique log-in usernames and passwords will be provided to those who have been delegated the role of randomising participants into the trial as detailed on the DEBI Delegation Log. The online randomisation system will be available 24 hours a day, 7 days a week, apart from short periods of scheduled maintenance. After participant eligibility has been confirmed, informed consent has been received, baseline data items have been provided, the participant can be randomised into the trial and a trial number allocated. Following randomisation, a confirmatory email will be sent to the randomising clinician, local Principal Investigator, and the local pharmacy. A randomisation notification will be sent to the Chief Investigator and NCTU. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacoeconomic, Therapy, Others (non-inferiority) |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Feanolla (Desogestrel) 75 mcg film coated tablets (Lupin Healthcare ltd, PL 35507/0195). [desogestrel] , Levest (Levonorgestrel 150mcg and Ethinylestradiol 30mcg) coated tablets [150 micrograms levonorgestrel, 30 micrograms ethinylestradiol] |
| Primary outcome measure | Participant-reported resolution of problem bleeding, with resolution defined as self-reported significant improvement in the bleeding pattern during the 90-day reference period. Improvement in problem bleeding will be measured by participants’ self-determination that their bleeding pattern has improved using a 5-point Likert scale, 90 days after the participants start their study medicine |
| Secondary outcome measures | Clinical effectiveness 1. Longest duration of consecutive non-bleeding (no bleeding or spotting) whole days within the 90 days measured using a 5-point Likert scale at Days 30 and 60 2. Total number of non-bleeding, spotting and bleeding days measured using a Daily bleeding diary during the 90-day treatment period 3. Number and duration of bleeding episodes (one or more consecutive days of bleeding, bounded by bleed-free days) measured using a Daily bleeding diary within the 90 days 4. Time to the longest consecutive non-bleeding days measured using a Daily bleeding diary within the 90 days Treatment acceptability and adherence 1. Acceptability of treatment (global and progestogenic side effects) measured using a Participant Questionnaire on days 30, 60 and 90 2. Adherence to treatment measured using a Daily bleeding diary Safety Discontinuation of allocated treatment and of implant measured using participant-reported discontinuation/removal of their implant in a Participant Questionnaire on days 30, 60 and 90 Cost-effectiveness 1. Quality of life (EQ-5D-5L and ICECAP-A) measured using participant-reported EQ-5D-5L and ICECAP-A on days 30, 60 and 90 2. Primary care, sexual health, and secondary care health resource use measured using a Participant Questionnaire on days 30, 60 and 90 3. Personal and out-of-pocket expenses arising from problem bleeding measured using a Participant Questionnaire on days 30, 60 and 90 4. Intention to continue the trial drug at 3 months measured using a Participant Questionnaire on days 30, 60 and 90 |
| Overall study start date | 01/04/2024 |
| Completion date | 31/07/2027 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target number of participants | 690 |
| Key inclusion criteria | 1. Female, or trans-male and non-binary people with a uterus, ovary/ovaries and vagina not using hormones other than etonogestrel implant 2. 16 – 45 years old 3 Etonogestrel implant user, with current implant in situ for at least 3 but no more than 24 months 4. Self-reported problem bleeding 5. Willing to complete daily bleeding diary for the trial duration 6. Able to provide Informed Consent 7. Sexually transmitted infection screening undertaken and high sensitivity pregnancy test negative at time of recruitment |
| Key exclusion criteria | 1. Current routine use of oral NSAIDs 2. Current use or use within the last 3 months of hormones or medications known to affect menstrual bleeding, including progestogens, estrogens, androgens, tranexamic acid, selective progestogen receptor modulators 3. Current use or use within the last 6 weeks of liver enzyme inducing medicines which induce the cytochrome CYP3A4 4. Postpartum < 6 weeks (UKMEC 3 or 4) 5. Current use or use within the last 6 months of gonadotrophin-releasing hormone analogues 6. Current use or use within the last 9 months of DMPA 7. Surgery to genital tract altering bleeding, including hysterectomy, bilateral-oophorectomy or endometrial ablation 8. Contraindication (UKMEC Category 3 or 4) or allergy to desogestrel or excipients (including soya bean oil) 9. Contraindication (UKMEC Category 3 or 4) or allergy to COCP containing levonorgestrel and ethinylestradiol or excipients 10. Established pathological reasons for abnormal uterine bleeding, including malignancy or endometrial hyperplasia, fibroids, cervical polyps or lesions (seen on speculum examination), endometrial polyp(s), adenomyosis, coagulopathy, ovulation disorder (e.g. polycystic ovary syndrome) 11. Current known sexually transmitted infection (If STI screening comes back positive then the participant will remain in the trial) 12. Currently pregnant (positive urinary pregnancy test) 13. Previous participation in this trial 14. Declines screening for sexually transmitted infection dual nucleic amplification test (NAAT) for Neisseria Gonorrhoeae and Chlamydia Trachomatis at the time of presentation 15. Declines a speculum examination to assess the cervix for abnormality or other cause for problem bleeding at the time of presentation 16. Declines examination of the implant insertion site to ensure palpable and present at the time of presentation |
| Date of first enrolment | 01/08/2025 |
| Date of final enrolment | 31/10/2026 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
University/education
Room A02, Nottingham Clinical Trials Unit, Applied Health Research
Nottingham
NG7 2RD
England
United Kingdom
| Phone | +44 (0)115 8231595 |
|---|---|
| DEBI@nottingham.ac.uk | |
| Website | https://www.nottingham.ac.uk/ |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/07/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Conference presentation 3. Publication on website 4. Submission to regulatory authorities 5. Other |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from debi@nottingham.ac.uk. Anonymised participant data may be shared with researchers external to the trial research team in accordance with the NCTU’s data sharing procedure and the National Institute for Health Care Research (NIHR) policy on the sharing of research data. All requests for data should be sent to the Nottingham Clinical Trials Unit. Participants consent to their anonymised information being used to support other research in the future and that it may be shared with other researchers. |
Editorial Notes
03/07/2025: The date of first enrolment was changed from 01/07/2025 to 01/08/2025.
09/05/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 09/05/2025
27/03/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)
