New Treatments for Troublesome Bleeding in Implanon Users

Menstrual Problem Clinical Trial

Official title:

Phase 4 Study Comparison of Two Combined Oral Contraceptive Regimens and an Intravaginal Hormonal Ring Against Placebo for Management of Bleeding Problems in Women Using Implanon, the Sub-dermal Contraceptive Implant

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01384331
• Other study ID #: R2011-01
• Secondary ID: ACTRN12611000617
• Status: Not yet recruiting
• Phase: Phase 4
• First received: June 27, 2011
• Last updated: June 28, 2011
• Start date: July 2011
• Est. completion date: April 2013

Study information

• Verified date: June 2011
• Source: Family Planning Association New South Wales
• Contact: Edith Weisberg, MB BS MM FRANZCOG
• Phone: +61 2 8752 4342
• Email: edithw[@]fpnsw.org.au
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

Most Implanon users experience a reduction in the frequency and volume of menstrual bleeding, but a substantial minority experience unpredictable and frequent and/or prolonged episodes of bleeding. This is a double blind, placebo controlled, randomised study with an additional randomised non-blinded arm. Two hundred women between the ages of 18-45 years, who are Implanon users with prolonged or frequent breakthrough bleeding (WHO definition) will be recruited and randomised into 4 equal-sized treatment groups of 50 women assigned to Marvelon 7 days or 21 days, NuvaRing 21 days or placebo. Recruited subjects will maintain a daily menstrual diary chart for a minimum of 90 days prior to randomisation, and will be enrolled into the treatment phase provided that they have met one of the World Health Organization criteria for prolonged or frequent bleeding Following the initial 90 day record, eligible women will begin designated treatment on day 1 of the next episode of bleeding or spotting. Analysis of the subsequent menstrual pattern will begin from day 1 of that bleeding/spotting episode and will continue through 90 days.

Description:

This is a double blind, placebo controlled, randomised study with an additional randomised non-blinded arm. Two hundred women between the ages of 18-45 years, who are Implanon users with prolonged or frequent breakthrough bleeding (WHO definition) will be recruited and randomised into 4 equal-sized treatment groups of 50 women assigned to Marvelon 7 days or 21 days, NuvaRing 21 days or placebo. Recruited subjects will maintain a daily menstrual diary chart for a minimum of 90 days prior to randomisation, and will be enrolled into the treatment phase provided that they have met one of the World Health Organization criteria for prolonged or frequent bleeding (in the 90 day reference period one episode of bleeding and/or spotting lasting > 10 days, or more than 4 bleeding/spotting episodes). Randomisation will be performed by computer generation of a random number table in blocks of ten, with equal numbers in each of the four groups. The medications will be packed in sequentially numbered and sealed opaque envelopes (independent of the investigators).

Following the initial 90 day record, eligible women will begin designated treatment on day 1 of the next episode of bleeding or spotting. Analysis of the subsequent menstrual pattern will begin from day 1 of that bleeding/spotting episode and will continue through 90 days. Analysis of the pre-treatment menstrual pattern will include the 90 days immediately preceding the bleeding episode in which treatment starts.

Women will participate in the study for approximately seven months depending on their bleeding pattern.

Data analysis:

Data will be analysed on an intention to treat basis, entered on SPSS and analysed prior to breaking the randomisation code. Frequency analyses will be undertaken for demographic data and means (SD) compared to check effectiveness of the randomisation scheme. Total number of days of spotting, bleeding, bleeding and spotting and number of episodes during the pre and post 90 days reference period will be entered.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: April 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy women aged 18-45 using the subdermal progestogen-only contraceptive implant and experiencing frequent or prolonged vaginal bleeding Willing to keep a menstrual diary for 6 months

Exclusion Criteria:

Women who have currently or previously had

• Heart attack or stroke

• Blood clot in a vein

• High blood pressure

• Severe liver or kidney disease

• Blood pressure > 135 mm systolic or >85 mm diastolic

• Migraine with aura

• Breast cancer or any genital cancer

• Severe chronic liver or kidney disease

• Women with known sensitivity to ethinyl oestradiol, progestogens

• Women taking phenytoin, carbamazepine or phenobarbitol

• Women who are pregnant

• Women who are lactating

• Women who are unwilling to keep a daily menstrual diary or otherwise unwilling to follow the study criteria

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Menstrual Problem
• Menstruation Disturbances

Intervention

Drug:
• Marvelon
7 days daily intake of oral capsule containing containing ethinyl oestradiol 30micrograms plus desogestrel 150 micrograms followed by 14 days oral placebo capsules 21 days daily intake of oral capsules containing ethinyl oestradiol 30micrograms plus desogestrel 150 micrograms 21 days NuvaRing contraceptive vaginal ring releasing ethinyl oestradiol 15micrograms plus etonorgestrel 120 micrograms dailyleft in situ for 21 days 21 days daily oral placebo capsules Treatment will be for one cycle of 21 days

Locations

Country	Name	City	State
Australia	Sydney centre for Reproductive Health Research, FPNSW	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Family Planning Association New South Wales	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Weisberg E, Hickey M, Palmer D, O'Connor V, Salamonsen LA, Findlay JK, Fraser IS. A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users. Hum Reprod. 2009 Aug;24(8):1852-61. doi: 10.1093/humrep/dep081. Epub 2009 Apr 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of days to stop bleeding after initiation of each treatment group and placebo	The number of days to stop bleeding after initiation of each treatment group and placebo determined from menstrual diaries completed by subjects	Within 3 weeks of starting therapy	No
Secondary	The mean total number of bleeding and spotting days during the 90 day "treatment" reference period	The mean total number of bleeding and spotting days during the 90 day "treatment" reference period compared with the pre-treatment reference period (calculated as percentage reduction) for each group and a comparison between treatment groups and placebo and compared to the other treatment groups determined from menstrual diaries kept for 90 days prior to starting treatment and for 90 days from initiation of treatment.	Six months after entering study	No