Clinical trial NCT01384331: New Treatments for Troublesome Bleeding in Implanon Users
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Menstrual Problem
Keywords: Implanon users
Frequent bleeding
Prolonged bleeding
Comparison of treatments
Placebo controlled
Randomly allocated tretment
Lead sponsor: Family Planning Association New South Wales
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-06-29
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The number of days to stop bleeding after initiation of each treatment group and placebo
timeFrame: Within 3 weeks of starting therapy
Secondary outcomes:
measure: The mean total number of bleeding and spotting days during the 90 day "treatment" reference period
timeFrame: Six months after entering study
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Sydney centre for Reproductive Health Research, FPNSW
state: New South Wales
Study officials:
affiliation: Family Planning NSW
name: Edith Weisberg, MB BS MM
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Ian S FRASER, BSC MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.