New Treatments for Troublesome Bleeding in Implanon Users

Sponsor

Family Planning Association New South Wales (Other)

Overall Status

Unknown status

CT.gov ID

NCT01384331

Collaborator

Merck Sharp & Dohme LLC (Industry)

200

Enrollment

Location

Arms

Duration (Months)

9.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Menstrual Problem	Drug: Marvelon	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 Marvelon ,placebo 7 days daily intake of oral capsule containing "Marvelon" ethinyl oestradiol 30micrograms plus desogestrel 150 micrograms followed by 14 days oral placebo capsules containing starch for 21 day treatment Cycle	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 Other Names: NuvaRing
Active Comparator: Marvelon 21 days daily intake of oral capsules containing ethinyl oestradiol 30micrograms plus desogestrel 150 micrograms for one cycle of 21 days	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 Other Names: NuvaRing
Active Comparator: NuvaRing 21 days NuvaRing contraceptive vaginal ring releasing ethinyl oestradiol 15micrograms plus etonorgestrel 120 micrograms dailyleft in situ for 21 days Treatment will be for 21 days	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 Other Names: NuvaRing
Placebo Comparator: Starch capsule 21 days daily oral placebo capsules Treatment will be for one 21 day cycle	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 Other Names: NuvaRing

Outcome Measures

Primary Outcome Measures

The number of days to stop bleeding after initiation of each treatment group and placebo [Within 3 weeks of starting therapy]
The number of days to stop bleeding after initiation of each treatment group and placebo determined from menstrual diaries completed by subjects

Secondary Outcome Measures

The mean total number of bleeding and spotting days during the 90 day "treatment" reference period [Six months after entering study]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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