Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02353247 |
| Other study ID # |
14-N0278 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 2015 |
| Est. completion date |
June 29, 2017 |
Study information
| Verified date |
February 2022 |
| Source |
Norton Healthcare |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The overall objective of this study is to confirm that oral progesterone is an effective way
to manage bothersome bleeding; thus increasing the rate of continuation of the etonogestrel
contraceptive implant in adolescents.
Description:
The investigators will conduct a prospective study of adolescents using the etonogestrel
contraceptive implant. Participants will be recruited from the Kosair Children's Hospital
Gynecology Specialists practice in Louisville, Kentucky. This practice provides care to a
diverse population of females, from a wide range of socioeconomic statuses, age birth to 25
years.
All patient presenting and choosing to have an implant placed will be offered participation.
All enrollments will be voluntary. Participants will not receive compensation for their
participation. After obtaining informed consent and assent, participants will provide
baseline demographic information, including: age, race/ethnicity, zip code of residence,
health insurance provider, number of current and past partners, use of prior contraceptive
methods, concomitant condom use, sexually transmitted infection history,smoking status,
weight and height. The date of etonogestrel implant insertion will be confirmed.
All patients using etonogestrel contraceptive implants will receive daily SMS texts in the
evening via the Qualtrics SMS program asking them to respond with their bleeding pattern that
day. The investigators will record responses according to the World Health Organization
definitions of bleeding: (a) bleeding day, (b) spotting day, (c) bleeding--- free day [see
Table I for WHO bleeding definitions]. At their initial follow---up visit 3 months after
Nexplanon insertion, the investigators will identify those who report "bothersome" bleeding
patterns. For the purpose of this study, "bothersome" bleeding will be defined as prolonged
and/or frequent bleeding, as characterized by World Health Organization---recommended
definitions of bleeding. The definitions are listed in Table I.
Bleeding day Any day with vaginal discharge containing blood that required more than 1
sanitary pad or tampon per day
Spotting day Any day with vaginal discharge containing blood that required at most one
sanitary pad or tampon per day Bleeding---free day A day during which neither bleeding nor
spotting was reported
Bleeding--- spotting episode One or more consecutive days during which bleeding or spotting
was entered in the diary, bounded by bleeding---free days
Amenorrhea No bleeding or spotting days throughout the 90---day reference period
Infrequent bleeding Less than three bleeding---spotting episodes in a 90---day reference
period, excluding amenorrhea
Normal frequency Three to five bleeding---spotting episodes in a 90---day reference period
Frequent bleeding More than five bleeding---spotting episodes in a 90---day reference period
Prolonged bleeding Any bleeding---spotting episode (uninterrupted) lasting more than 14 days
in the 90---day reference period
Table I: WHO bleeding descriptions and patterns
Norethindrone acetate (aygestin) will be used to manage bothersome bleeding. Patients will be
prescribed aygestin 5 mg by mouth twice daily for one month, followed by aygestin 5 mg by
mouth once daily for two months. Medication will then be discontinued. Patients will be
evaluated in the office three months after medication initiation, and then again six months
after medication initiation. If the patient is unable to take norethindrone acetate
(aygestin) due to medical contraindications or cost, they will receive medroxyprogesterone
acetate (provera) 10 mg once daily as alternate oral progesterone. Figure 1 below highlights
the study design.
Contraceptive implant inserted & enrollment in the study
Bleeding patterns recorded via SMS text x 3 months
Office visit
Normal bleeding pattern Bothersome bleeding pattern
Continue to record bleeding pattern Aygestin 5 mg PO BID x 1 month*
Continue to record bleeding pattern Aygestin 5 mg PO daily x 2 months
Continue to record bleeding pattern No mediation x 3 months
Office visit Office visit
*Or provera 10 mg PO daily x 3 months
Figure 1: Study design
During the aygestin administration, patients will again receive daily SMS texts in the
evening via the Qualtrics SMS program asking them to respond with their bleeding pattern that
day. The investigators will record responses according to the World Health Organization
definitions of bleeding: (a) bleeding day, (b) spotting day, (c) bleeding--- free day.
Patients not reporting bothersome bleeding after the initial 90 days will continue to record
bleeding via SMS texts for the next 6 months to serve as the control group (normal bleeding
group).
All completed demographic data collection forms and electronic menstrual calendars will be
kept in a database, de---identified, and stored on a password--- protected computer. Study
size will be a convenience sample. Based on the current rate of etonogestrel implant
insertions in our practice, it is anticipated that 30 participants can be recruited over a
six---month period of time.
Data Collection and Analysis
All patients who meet the inclusion criteria and enroll in the study will be sent a text
message daily for 90 days (3 months). The daily message will prompt the participant to
indicate the bleeding level for the day. This single question will have 4 options:
1. Bleeding Day
2. Spotting Day
3. Bleeding Free Day
4. Prefer not to answer today.
On day 90, descriptive tallies of the responses will be done. Using SPSS v20, an algorithm
will count the number of bleeding days, spotting days, and bleeding free days and prefer not
to answer (PNA) days; the data record for each participant will contain four count variables
(bleeding, spotting, free, PNA). Secondly, the algorithm will identify and tally -according
to WHO guidelines in Table 1 --- bleeding---spotting episodes (BSE),amenorrhea (AM),
infrequent bleeding (IF), normal frequency of bleeding (NF), frequent bleeding (FB), and
prolonged bleeding (PB).
Participants who have at least a single episode of FB or PB will be assigned the label of
"bothersome bleeding". Those without a single episode of FB or PB will be labeled "normal
bleeding". Participants in the Bothersome Bleeding group will be offered aygestin to control
the bothersome bleeding. Participants in the Normal Bleeding group will continue as before,
with no additional medications. Following the principle of intent---to---treat, data from
those in the Bothersome Bleeding group will be assigned to the aygestin group, despite that
they are not taking it. During the first month, participants in the Bothersome Bleeding group
will take one 5 mg tablets of aygestin twice daily (morning and evening). After 30 days, the
dose of aygestin will be halved, such that only one 5 mg tablet is taken daily. Sixty days
later, the Bothersome Bleeding group will discontinue aygestin. Ninety days later, both the
normal group and the Bothersome Bleeding group will be re-evaluated.
Data Analysis
A descriptive table will be used to sort participants into Normal Bleeding and Bothersome
Bleeding. Non---parametric and parametric statistics will be used to compare the demographics
of these two groups.
A dose---response curve covering six months will be plotted for the Bothersome Bleeding group
to visually reveal the impact of one month of 10 mg of aygestin vs. two months of 5 mg
aygestin vs. three months 0 mg of aygestin. Plotted on the curve will be the group averages
of the daily bleeding value (1 for no bleeding, .5 for spotting, 0 for bleeding). A second
no---dose curve will be added to the X---Y plot for the six months of data from the Normal
Bleeding group.
Repeated Measure Multivariate Analysis of Variance (RM---ANOVA) with a Between--- Subjects
variable included, will be conducted (assuming sufficient data is available - e.g., low PNA
rates) to compare the first 30 day average bleeding value, the 90 day bleeding average, and
the 180 day bleeding average between the two groups. Planned post---hoc comparisons will
evaluate changes between the control group and intervention group at the three time points.
Additional analyses may also include regression analysis to assess for predictive factors
related to response to aygestin.
