New Treatments for Troublesome Bleeding in Implanon Users - Full Text View

Purpose

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	Intervention	Phase
Menstrual Problem	Drug: Marvelon	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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

Resource links provided by NLM:

MedlinePlus related topics: Menstruation

Drug Information available for: Estradiol Ethinyl Estradiol Estradiol cypionate Estradiol valerate Estradiol acetate Estradiol hemihydrate Desogestrel Etonogestrel

U.S. FDA Resources

Further study details as provided by Family Planning Association New South Wales:

Primary Outcome Measures:

The number of days to stop bleeding after initiation of each treatment group and placebo [ Time Frame: Within 3 weeks of starting therapy ] [ Designated as safety issue: No ]
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 [ Time Frame: Six months after entering study ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	200
Study Start Date:	July 2011
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Marvelon 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: Marvelon 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: Marvelon 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: Marvelon NuvaRing

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

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384331

Contacts

Contact: Edith Weisberg, MB BS MM FRANZCOG	+61 2 8752 4342	edithw@fpnsw.org.au
Contact: Lorraine Edney, RN	+61 2 8752 4381	lorrainee@fpnsw.org.au

Locations

Australia, New South Wales
Sydney centre for Reproductive Health Research, FPNSW	Not yet recruiting
Sydney, New South Wales, Australia, 2131
Principal Investigator: Edith Weisberg, MB BS MM

Sponsors and Collaborators

Family Planning Association New South Wales

Merck

Investigators

Principal Investigator:	Edith Weisberg, MB BS MM	Family Planning NSW
Principal Investigator:	Ian S FRASER, BSC MD	University of Sydney

More Information

Publications:

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. Epub 2009 Apr 15.

Responsible Party:	Dr Edith Weisberg, Sydney Centre for Reproductive Health Research, Family Planning NSW
ClinicalTrials.gov Identifier:	NCT01384331 History of Changes
Other Study ID Numbers:	R2011-01, ACTRN12611000617965
Study First Received:	June 27, 2011
Last Updated:	June 28, 2011
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Family Planning Association New South Wales:

Implanon users
Frequent bleeding
Prolonged bleeding

Comparison of treatments
Placebo controlled
Randomly allocated tretment

Additional relevant MeSH terms:

Hemorrhage
Menstruation Disturbances
Pathologic Processes
Contraceptive Agents
3-keto-desogestrel
Desogestrel
Contraceptives, Oral
Contraceptives, Oral, Combined
Ethinyl Estradiol
Reproductive Control Agents

Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Progestins
Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on May 16, 2013