Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04832906 |
| Other study ID # |
FMASU M D 71/2019 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 13, 2019 |
| Est. completion date |
March 13, 2021 |
Study information
| Verified date |
April 2021 |
| Source |
Ain Shams Maternity Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Study objective: To prove that Ulipristal acetate is an effective line of management for
uterine fibroids by causing a significant decline in fibroid volumes resulting in a
substantial relief of fibroid-related symptoms, and to compare its results with those of
uterine artery embolization.
Design: A randomized control trial. Setting: Maternity Hospital, Ain Shams University.
Patients: Women with symptomatic uterine fibroids.
Interventions: 70 women were randomly assigned to either Ulipristal Acetate (UA) group or
uterine artery embolization (UAE) group (35 in each group). Both groups were followed up to
detect the decline in fibroid size as well as the improvement of symptoms.
Description:
Inclusion Criteria:
Women with symptomatic uterine fibroids were recruited into the study after fulfilling the
following criteria:
- Their age should range from 35 to 50 years.
- Their body mass index (BMI) should range from 18 to 35 Kg/m2.
- The presence of multiple symptomatic type 2, 3, 4, 5, or 6 uterine fibroids according to
the FIGO classification.
- The dominant fibroid diameter should range from 4 to 8 cm as assessed by ultrasound.
- They should not be seeking future fertility.
- They should be refusing any surgical intervention whether myomectomy or hysterectomy.
Exclusion Criteria:
1. Post-menopausal status or premature ovarian failure.
2. Type 0, 1 and 7 uterine fibroids according to FIGO classification.
3. Previous myomectomy or any uterine surgery.
4. Previous or ongoing hormonal treatment.
Sampling Method:
The study sample will be a "convenient sample" where women fulfilling the inclusion criteria
and consenting to participate in the study will be recruited.
Sample Size justification:
The study will include 70 women with symptomatic uterine fibroids who will be randomized into
two groups with 35 women in each group.
The required sample size has been calculated using the PASS 15 Power Anal-ysis and Sample
Size Software (PASS©) version 15 (2017); NCSS, LLC. Kaysville, Utah, USA.
The main outcome measure is the reduction in fibroid volume. The secondary outcome measures
are symptoms relief and improvement in quality of life.
A previous study reported that Ulipristal Acetate (UA) was comparable to uterine artery
embolization (UAE) as regards the percentage of reduction in fibroid volume with median
(interquartile range) percentage reduction of 48.1 (24.8 - 66) % versus 47.3 (29.5 - 69.5) %
for UPA and UAE respectively (Czuczwar et al., 2015).
Using the methods described by Wan et al (2014) and Luo et al (2018), we calculated that the
mean ± SD percentage of reduction in fibroid volume was 44.0 ± 28.5 % versus 48.9 ±32.3 % for
UPA and UAE respectively, with mean difference of 4.9 % and common within group SD of 30.5%.
Taking into consideration a "drop-out rate" of about 10%, due to loss of follow up or
withdrawal from the study, it is estimated that a sample size of 35 patients per group
achieves 80% power using a one-sided equivalence test with a significance level of 5%
(alpha-error = 0.05), when the difference between the two means is 4.9 %, common within group
SD is 30.5 %, and equivalence limits are -25% and 25%.
On the other hand, this sample size achieves a power of 82% to detect a statistically
significant difference between the two groups as regards the symptoms scores and measures of
ovarian reserve (AFC and AMH) for an effect size equivalent to a Cohen's d of 0.75 (i.e.,
0.75 common SD) using a two-sided unpaired t-test with the same significance level of alpha =
0.05.
These equivalence limits and effect size have been targeted, as they may be considered
clinically important.
Informed consent:
The nature and scope of the clinical study will be explained in an understand-able way to the
patients and an informed consent form, in Arabic language, including all the study
procedures, advantages and possible risks and specifying who informed the patient, will be
provided and the patient must sign on it before participation. The study protocol and patient
informed consent will be reviewed and approved by the Ethics Committee of the Obstetrics and
Gynecology Department, Ain Shams University.
Funding:
This study will be funded by the researcher himself and Ain Shams University
Randomization and Allocation concealment:
The participants will be randomly assigned into one of the two study groups using a computer
random sequence generator. The randomization will be made using sequentially numbered, opaque
sealed envelopes; each envelope contains the method of intervention according to the random
sequence and will be opened just before the intervention.
Study Procedures:
All participants will undergo full assessment before starting either treatment options. This
assessment will include:
Detailed History:
- Personal history: including patient's full name, age, marital status, parity, occupation
and residence will be recorded.
- Menstrual history: including age of menarche, D/C, amount of menstrual flow and
associated dysmenorrhea.
- Contraceptive history: to exclude other causes for uterine bleeding.
- Past medical history of Diabetes Mellitus, hypertension, bronchial asthma, cardiac
diseases, anemia, etc.
- Past surgical history of uterine surgeries.
- History of present illness with detailed analysis of each patient's complaint whether
abnormal uterine bleeding, dysmenorrhea and pelvic pressure symptoms such as urinary
urgency or constipation.
Physical Examination:
- General examination including: Pulse, blood pressure, temperature, body mass index
(BMI), auscultation of lungs and heart, and complex-ion as pallor due to anemia caused
by heavy bleeding.
- Abdominal examination: inspection for any scar, palpation of the abdomen for any
tenderness and for pelviabdominal masses.
- Pelvic examination: complete bimanual examination for uterine size, mobility and
palpable uterine fibroids.
Investigations:
- Baseline hemoglobin, hematocrit, and blood grouping.
- Blood chemistry: AST, ALT, serum creatinine and RBS.
- Trans-vaginal ultrasound for uterine volume and fibroid location, volume and maximum
diameter. Uterine volume (expressed in cubic centimeters) will be calculated by
measuring the maximum length, antero-posterior and transverse diameters of the uterine
corpus, using the US device software formula for calculation of the uterine volume.
Myoma volumes will be measured by using the existing 2-dimensional US methods. The FIGO
classification system (figure 1) will be used for defining the myoma location.
Study groups:
Patients recruited in this study will be randomized into one of the following study groups:
1. Group A "Ulipristal Acetate (UA) - Fibristal group" (n=35):
Patients within this group will receive oral Ulipristal Acetate (Fibristal ©) 5 mg / day
starting from the first day of menstrual bleeding, and for 3 months (period of the
study).
2. Group B "Uterine artery embolization (UAE) group" (n=35):
Patients within this group will undergo bilateral selective uterine artery embolization,
during which polyvinyl alcohol (PVA) particles will be administered via a catheter followed
by capping with a plug of gelatin sponge. The end point for embolization is to have a static
column of contrast in the uterine artery, with only a stump filling when the internal iliac
artery was injected. The gelatin sponge cap was thought to both complete the occlusion of the
uterine artery and to prevent PVA particles from being drawn out of the uterine artery by the
Venturi effect, which would result in non-target embolization.
Follow up:
Each patient within both groups will be subjected to follow-up trans-vaginal ultrasound (US)
3 months after Ulipristal acetate (UA) therapy or after uterine artery embolization (UAE)
session to detect the decline in uterine fibroid volumes in comparison to their baseline. To
reduce inter-observer variability associated with ultrasound imaging, measurements will be
always taken by the same sonographer.
Each patient within both groups will be evaluated clinically for the symptoms reported at
least 1 month before starting the treatment (baseline) and 3 months after Ulipristal acetate
(UA) therapy or after uterine artery embolization (UAE) session. Durability of the used
treatment line will be tested by follow up after one year from initiating therapy.
Fibroid-related heavy menstrual bleeding (HMB) will be evaluated by the pictorial blood
assessment chart score (figure 2). This instrument is a self-administered pictorial chart
that takes account of the number of sanitary pads and tampons used, presence of blood clots,
and episodes of bleeding. The 1-month pictorial blood assessment chart score was calculated
from the addition of daily scores for 28 days. A score of higher than 100 during the first 8
days of menstruation will be defined as heavy menstrual bleeding (HMB).
Subjective feelings of pelvic pressure, urinary urgency, and constipation will be recorded on
a simplified questionnaire containing 2 categories defined as "absent "and "present." The
visual analog scale (VAS) pain score (figure 3) will be used to determine the presence or
absence of pelvic pain.
Statistical Methods:
Data will be analyzed using Intention to treat (ITT) analysis. According to Fisher et al
(1990), the ITT analysis includes all randomized patients in the groups to which they were
randomly assigned, regardless of their adherence with the entry criteria, regardless of the
treatment they actually received, and regardless of subsequent withdrawal from treatment or
deviation from the protocol.
In other words, ITT analysis includes every subject who is randomized according to randomized
treatment assignment. It ignores non-compliance, protocol deviations, withdrawal, and
anything that happens after randomization. ITT analysis is usually described as "once
randomized, always analyzed".
ITT analysis avoids overoptimistic estimates of the efficacy of one of the two interventions
resulting from the removal of non-compliers by accepting that noncompliance and protocol
deviations are likely to occur in actual clinical practice.
Efficacy of the two study interventions will be compared using Odds ratio (OR), Relative risk
(RR), Number needed to treat (NNT) and Number needed to harm (NNH).
Data will be analyzed using IBM© SPSS© Statistics version 23 (IBM© Corp., Armonk, NY).
Normally distributed numerical data will be presented as mean and SD, and skewed data as
median and interquartile range. Qualitative data will be presented as number and percentage.
Normally distributed numerical data will be compared using the unpaired t test and skewed
data using the Mann-Whitney test. Categorical data will be compared using the Pearson
chi-squared test or Fisher's exact test, if appropriate. A two-sided p-value <0.05 will be
considered statistically significant.
