Endometriosis Clinical Trial
Official title:
Maintenance Therapy of LNG-IUS in Conjunction With the GnRH Agonist to Prevent the Recurrence of Symptomatic Endometriosis After Conservative Surgery: A Prospective Randomized, Phase III Trial
The recurrence rates of endometriosis reported in women 5 years after therapy with
gonadotropin releasing hormone (GnRH) agonist were 74% for severe disease . No strategies to
prevent the recurrence of endometriosis have been uniformly successful. Local progesterone
treatment of endometriosis-associated dysmenorrhea with a levonorgestrel-releasing
intrauterine system (LNG-IUS) for 12 months has resulted in a significant reduction in
dysmenorrhea, pelvic pain and dyspareunia; a high degree of patient satisfaction; and a
significant reduction in the volume of rectovaginal endometriotic nodules. LNG-IUS may
become a more important option if a long-term medical suppression of endometriosis.
Based on literature review, I hypothesized that maintenance therapy of LNG-IUS in
conjunction with the GnRH agonist could lower the recurrence rates endometriosis after
conservative surgery. We try to answer the question whether maintenance therapy of LNG-IUS
in conjunction with the GnRH agonist could lower the recurrence rates and thus extend the
symptom-free interval (menorrhagia and dysmenorrhea) as compared to GnRH agonist alone after
conservative surgery in severe endometriosis cases.
Participants:
This post-surgical medical therapy trial will be undertaken among patients with
moderate-severe symptomatic endometriosis (rASRM score >16, according to the American
Society for Reproductive Medicine) or adenomyosis. Symptomatic endometriosis means
menorrhagia or dysmenorrhea. All patients were surgically treated by a conservative approach
(means preserve uterus and ovary).
Interventions:
In all patients, were prescribed 600 mg elemental Ca and 400 IU vitamin D (bid). The first
group of patients receive LNG-IUS for 5 years and GnRH agonist (triptorelin 3.75 mg, sc
q28day) for 24 weeks.
The second group of patients receive GnRH agonist (triptorelin 3.75 mg, sc q28day) alone for
24 weeks.
Patients were evaluated every month for 24 weeks, and at 3,6,9,12,15,18,21,24 months after
the end of medical treatment.
Objectives and outcomes:
The main objective of this trial was to assess the clinical efficacy of LNG-IUS maintenance
therapy to prevent recurrence of endometriosis. Thus the primary outcome measures of this
trial is the recurrence rate of endometriosis.
During this trial, recurrence was defined as elevation of CA125 (6) or endometriosis lesion
in sonography or symptoms suggesting endometriosis including menorrhagia or dysmenorrhea.
The pain score diary was based on the visual analogue scale in which patients recorded the
occurrence an intensity of their pain daily. VAS consists of a subjective evaluation of the
pain on a scale of 10 in which 0 is no pain and 10 the most severe pain (7).
Bleeding and menorrhagia were assessed as: 0= no bleeding; 1=spotting (light bleeding not
requiring sanitary protection); 2=light bleeding (light bleeding requiring sanitary
protection); 3=normal bleeding (bleeding similar to normal menstrual blood flow); and
4=heavy bleeding (bleeding exceeding normal menstrual blood flow). No bleeding was defined
as 30 consecutive days with bleeding score 0 (8).
Randomization process:
Treatment allocation was performed in accordance with a computer-generated randomization
sequence using numbered, sealed envelopes.
Evaluation of efficacy:
Sample size:
In calculating the sample size required, the primary assessment was the recurrence rates. A
31% recurrence rate after laparoscopic reproductive surgery and post-surgical treatment with
a GnRH agonist has been reported (9). We expected a decrease in recurrence rates after
laparoscopic conservative surgery and post-surgical treatment with GnRH agonist plus
LNG-IUS. A difference of 25% between the allocated treatments was considered significant. To
have a 90% chance of detecting such a difference at an overall significant level of 5%, 40
patients for each group were required.
Endpoints:
We will follow the patients for 2 years, after the end of GnRH agonist medical treatment.
Thus the primary outcome measures of this trial is the recurrence rate of endometriosis.
The main objective of this trial was to assess the clinical efficacy of LNG-IUS maintenance
therapy to prevent recurrence of endometriosis.
Statistical analysis plan:
The cumulative proportion of recurrences by plotting percent recurrences as a function of
time was estimated by the method of Kaplan and Meier. The survival curves for each allocated
treatment were compared with the log-rank test.
For quantitative variables with normal distribution, the parametric t-test was used; in the
case of the other variables, the non-parametric Mann-Whitney test was applied. For
qualitative variables, x2-test or Fisher's exact test were used. For dependent variables
with numerical scores referring to long-term measurement, multivariate analysis of variance
( MANOVA) was used.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
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