Use of Ulipristal Acetate in Induction of Second Trimester Missed Abortion in Women With Previous Caesarian Section: A Randomized Controlled Trial.
Phase: PHASE4
Conditions: Induction of Second Trimester Abortion
Sponsor: Ain Shams University

                
 
 
Title of the Protocol: Use of Ulipristal Acetate in Induction of Second Trimestric 
Missed Abortion  in Women with Previous Caesarian section: Randomized Controlled 
Trial. 
 Document date :  November 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                
 
Background  
Miscarriage is a common event in a woman’s life. Approximately 20% of 
clinically recognized pregnancies end in a miscarriage [1] Most miscarriages occur 
before 12 weeks and it has been estimated that only 2–3% of pregnancies end 
spontaneously in the second trimester. Second-trimester pregnancy loss has been 
defined as miscarriage diagnosed between the duration of gestation of 12–24 weeks 
[2]. According to the World Health Organization, miscarriage is defined as the 
premature loss of a fetus at < 22weeks of the pregnancy and weighing < 500 g. [3]  
Medical management of miscarriage and induced abortion has become the gold 
standard in clinical practice. However, the treatment of second trimester miscarriage 
has been addressed in only few research studies. In a recent systematic review of 
medical treatments for incomplete miscarriage, no randomized trials focused 
specifically on the treatment of miscarriage beyond    week s gestation were 
identified [4]. Thus the clinical practice on the treatment of late miscarriages is mainly 
based on the knowledge derived from studies on second trimester induced abortion. 
[6] 
Medical abortion is the termination of pregnancy with use of medications to 
induce a process similar to a miscarriage. It is an alternative to aspiration curettage. 
Use of a combination of mifepristone (an antiprogesterone) and misoprostol (a 
prostaglandin) is the primary method of medication abortion used according to the  
American College of Obstetricians and Gynecologists . [7]  
 
 
 

                
Ulipristal is a selective progesterone receptor modulator (SPRM) with primarily 
antiprogestin activity. Due to its antiprogestin activity it is highly effective for use in 
emergency contraception. It’s primary mechanism of action is delay of ovulation, but 
endometrial effects that may affect implantation may also contribute to efficacy. [9]  
A  Cochrane review demonstrated that medical abortion in the second trimester 
(13–28 weeks) using the combination of mifepristone and misoprostol appeared to 
have the highest efficacy and shortest abortion time interval compared to other 
medical regimens.  [10 
 Mifepristone may be used in combination with misoprostol to decrease the 
induction-to-abortion interval and minimize pain. By opposing the activity of 
progesterone, mifepristone elicits a variety of effects that make the uterus more 
susceptible to abortion. These effects include cervical dilation, decidual necrosis, 
increased endogenous prostaglandin production, and increasing uterine sensitivity to 
exogenously administered prostaglandin. Mifepristone administration gradually elicits 
a five-fold increase in sensitivity to prostaglandin 24 to 48 hours after its 
administration [11]. The synergy between mifepristone and prostaglandin permits 
greater efficacy of prostaglandin at lower doses, potentially minimizing side effects 
[12]. 
                  The improved efficacy with mifepristone was best illustrated in a randomized 
trial that compared second-trimester abortion with misoprostol (buccal 400 mcg, then 
200 mcg every six hours) preceded by either mifepristone (oral 200 mg) or placebo 
(oral vitamin C).Women in the mifepristone group had a significantly shorter median 
procedure time (10 versus 18 hours). In addition, the mifepristone group had a non 
significant association with lower rates of retained placenta (3.1  
 

                
versus 6.3 percent) and analgesic requirements (27.2 versus 39.3 mg morphine). Side 
effects were similar between groups. [13]. 
 
What is already known on this subject? AND What does this study add? 
Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved 
for use as an emergency contraceptive and for preoperative treatment of uterine 
fibroids. It has not been used as an abortifacient drug in previous studies. However, 
due to its antiprogestin activity, like its family member Mifeprostone, it could be 
effective if it is used alongside Misoprostol according to FIGO guidelines for 
induction of abortion. This may decrease the time taken for patients to abort, may 
increase the success rate of having a complete abortion thus decreasing the need for 
aspiration& hysterotomy. All this, would lead to less morbidity, shorter hospital 
admission stay, better psychological wellbeing for patients and a decrease in all 
hospital costs 
 
The aim of this work is to assess the effectiveness and safety of Ulipristal 
Acetate in the management of 2nd trimestric missed abortion along with misoprostol in 
pregnant women with previous caesarean section versus the use of misoprostol only 
with placebo as regards the time needed for abortion. 
Research Question 
In pregnant women with 2nd trimestric missed abortion with previous caesarean 
section , does Ulipristal Acetate decrease the time interval to achieve abortion when 
combined with Misoprostol in comparison to Misoprostol alone? 
 
 
 

                
Hypothesis 
In  pregnant women with 2nd trimestric missed abortion with previous caesarean 
section , Ulipristal Acetate may decrease the time interval to achieve abortion when 
combined with Misoprostol in comparison to misoprostol alone. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                
Methods 
 
Study Design 
Type of Study: A Randomized Controlled Trial. 
Study Setting: Ain Shams University Maternity Hospital. 
Study Period: Starting from January 2019 to January 2020. 
Participants 
Study Population: Women with 2nd trimestric missed abortion  with previous 
caesarean section undergoing medication abortion attending  either  outpatient clinic 
or emergency room 
Eligibility Criteria: 
           Inclusion Criteria:  
- Women with 2nd trimestric missed abortions  
- Gestational age  13-26 weeks. 
- Women with a previous caesarian section scar,(Para-1CS till Para-4CS). 
- Women counseled and chose medication abortion rather than surgical evacuation 
          Exclusion Criteria:  
- Women with an accompanying medical disorder such as: Preeclampsia, DM or 
Heart disease. 
- Primigravida women or non scarred uterus. 
- Women with previous myomectomy or hysterotomy scar or upper segment 
caesarean section scar.  
 

                
- Induction of abortion in women with congenital fetal malformations or positive 
fetal pulsations due to medical disorder 
- Women with placenta previa. 
- Allergy or contraindications to either Ulipristal acetate or Misoprostol. 
- Women with inevitable abortion in the form of vaginal bleeding or uterine 
contractions. 
All women who met the inclusion criteria will be assessed. 
 This assessment will include: 
Detailed History: 
Personal history (Maternal age, weight, height).  
Obstetric history . Gravidity, Parity, previous operative delivery.  
Any associated complication during pregnancy.  
Menstrual history (Last menstrual period).   
Maternal medical history (Hypertension & Coagulopathies).  
Physical Examination: 
i. 
General examination: a. Vital signs b. Chest and heart examination  
ii. 
Abdominal examination: a. Gestational age b. Fetal weight, amount of liquor, 
fetal lie and presentation, fetal heart sounds c. Uterine contractions and scar of 
previous surgeries 
iii. 
Vaginal examination to detect cervical dilatation, consistency, position and 
length. 
  
 
 
 
Investigations: 

                
 CBC ,Liver Function, Kidney function, Random blood sugar, Prothrombin time 
(PT) 
Obstetric ultrasound study: For assessment of gestational age, fetal life, 
implantation site of the placenta and fetal weight. 
 
Interventions 
The study sample, will be divided into two groups as follows: 
Group A: will receive Ulipristal acetate  0mg, starting misoprostol  2 hours later 
 00µg every 6 hours buccal according to FIGO guidelines 20 7. 
Group B: will receive placebo tablet then  2 hours later start misoprostol  00µg 
every 6 hours buccal according to FIGO guidelines 20 7.  
 
Then women in both groups will have rest for 24hours after 5 doses of 
misoprostol 
and restart misoprostol-only in both groups with the same above regimens, repeating 
the same sequence for two weeks unless there is excessive bleeding or infection. If 
failed, patient will proceed to hysterotomy. 
 
Primary outcome 
1. Induction-to-abortion interval time. 
 
Secondary outcome 
1. Success rate for complete evacuation between both groups. 
2. Occurrence of side effects: i) Nausea ii) Vomiting iii) Fever iv) Pain, between 
both groups. 
3. Rate of uterine rupture between both groups. 
 

                
4. Amount of blood loss, as a comparison between both groups. 
5. Rate of hysterotomy between both groups. 
 
Sampling Method: 
Sample Size: A pilot sample was used primarily, to accurately calculate the main 
study sample. According to Julious SA. (6), a pilot sample size of 24 ( 2 per arm) was 
used. The objective is not to prove superiority of the treatment but to test trial 
procedures and processes and to get estimates of parameters for the main trial sample 
size calculation. Women fulfilling the inclusion criteria and consenting were randomly 
assigned to either group 
 
Randomization, Allocation and Concealment: 
A computer generated list via MedCalc® Software, version 13.2.2 will be used 
for randomization, assigning each participant number to either study group using 
sequentially numbered, otherwise identical, sealed envelopes (SNOSE), each  
 
 
 
containing a 2-inch by 2-inch paper with a written code designating the assigned 
group. These papers were placed in a folded sheet of aluminum foil fitted inside the  
envelope. To ensure concealment, efforts will be taken to assure absence of any 
detectable differences in size or weight between intervention and control envelopes. 
Envelopes will be chosen to be opaque and lined inside with carbon paper. Envelopes 
will be opened sequentially after writing the subject’s tracking information on the 
envelope so that the carbon paper served as an audit trail. At the time of procedure, the 

                
responsible investigator will open the envelope to reveal the assignment, and she will 
introduce the planned method.  
 
After enrollment, the cases will be randomly allocated into two groups: 
• 
Group A(n=30): Will be the case group, it includes cases who will receive 
Ulipristal Acetate plus Misoprostol. 
• 
Group  B(n=30): will be the control group, it includes cases who will receive 
Misoprostol only plus a structurally similar placebo drug manufactured at Ain Shams 
Pharmacology department.  
Ethical Considerations:  
The nature and scope of the clinical study will be explained in a form understandable 
to the patient and an informed consent document, in Arabic language, contains all 
locally required elements and specifies who informed the patient, will be provided and 
the patient must give written consent.  Patients should be counseled that medication 
abortion takes longer and that they may have a greater awareness of blood loss and 
passage of pregnancy tissue with high risk of rupture uterus (0. %)[ 6] and blood 
transfusion. 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. 
 
 
 
 
 
 
 
 

                
 
 
 
 
 
 
 
 
 
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