Clinical trial NCT03714880
Conditions: Second Trimester Abortion
Sponsor: University of California, Davis
Start date: 2019-04-26; Completion date: 2021-02-26
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators plan to study the role of mifepristone prior to the placement of cervical osmotic dilators to evaluate if the medication helps increase the number of dilators. This may help improve safety of dilation and evacuation (D\&E) procedures.

Detailed description:
No clear guideline currently exists for best practices involving cervical preparation for women planning dilation and evacuation at 20 weeks and greater. The investigators plan to perform a pilot, randomized, double-blind, placebo-controlled trial. On day 1, 66 participants will receive mifepristone 200 mg orally or placebo 18-24 hours prior to osmotic dilator (Dilapan-S 4-mm) placement (day 2). On day 3, participants will have a D\&E procedure. Enrollees will be 18 weeks 0 days to 23 weeks 6 days gestation on the day of the procedure. The primary objective is to evaluate the role of adjunctive mifepristone the day prior to osmotic dilator placement for dilation and evacuation procedures. The primary outcome will be the number of dilators successfully placed. Investigators will compare the number of dilators placed between study arms stratified by gestational age. Secondary outcomes include cervical dilation at time of procedure, proportion of women requiring mechanical dilation at time of surgery, provider impression on ease of procedure and/or difficulty in dilating the cervix when clinically required, and overall complications. Complications or adverse events include cervical laceration requiring repair, perforations, blood transfusions, ED visits, hospitalizations, infection, additional surgical procedures, or extramural deliveries.

Arms: arm 1: Participants ingest mifepristone 200 mg oral medication once 18-24 hours prior to dilator placement arm 2: Participants ingest placebo oral medication once 18-24 hours prior to dilator placement
Interventions: intervention 1: Mifepristone 200 MG intervention 2: Placebo Oral Tablet
Intervention descriptions: intervention 1: Ingestion of study medication vs placebo intervention 2: Ingestion of study medication vs placebo

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Mifepristone prior to osmotic dilators for dilation and evacuation cervical preparation:  
A randomized, double-blind, placebo-controlled pilot study 
Clinicaltrials.gov: NCT03714880 
Protocol Proposal original submission October 2018 
 
 


1.1 Design methodology 
1.1.1 
Research design and general methodological approach 
The planned research design is a double-blind, placebo-controlled randomized trial.  
A. Study arm: mifepristone 200 mg orally 18-24 hours prior to osmotic dilator placement 
B. Control arm: placebo oral medication 18-24 hours prior to osmotic dilator placement 
The total number of women will be 66 and 33 women will be allocated to each group 
(Appendix – CONSORT Flow Diagram).  
1.1.2 
Criteria for the selection of subjects 
Inclusion criteria: 
A. Women planning dilation and evacuation with cervical dilator placement at gestational 
ages 20 weeks 0 days to 23 weeks 6 days on procedure day 
B. English-speaking/writing 
Exclusion criteria: 
A. Allergy to mifepristone 
B. Any condition that in the opinion of the investigator could impede study participation or 
collection of study data 
1.1.3 
Subject recruitment and allocation 
Participant identification 
Potential participants will be identified either at time of referral to UC Davis Family Planning 
Center from outside clinics after dating ultrasound is performed or when presenting directly 
for dating ultrasound at UC Davis Family Planning Center.  
Pre-visit phone call 
For women who have been referred to UC Davis and have already had a dating ultrasound, 
research staff will call to explain the study. For women not interested in the study, a 
standard pre-operative visit per clinic guidelines will be scheduled. For women who are 


interested in enrolling in the study, a screening and enrollment visit with be scheduled. 
Women will be notified that they will be randomly allocated to mifepristone or placebo 
medication. 
1.1.4 
Description of the drugs and devices to be studied 
Mifepristone exerts anti-progestin activity by binding with high affinity to progesterone 
receptors and causing an increase in glycosaminoglycans, such as hyaluronic acid, increases 
collagenase activation and tissue water content 14-17. These actions promote softening and 
dilation of the cervix 14,15 and also increase the myometrial response to exogenous 
prostaglandins, such as misoprostol 17.  
1.1.5 
Admission procedure 
Day 1: Screening and Enrollment 
This visit is scheduled after a pre-visit phone call or at the time of the dating ultrasound visit. 
Pre-operative examination and operative consents will be reviewed and signed per usual 
practice. Research staff will review the study and obtain informed consent for the study. 
Office or formal radiologic ultrasounds will be performed based on clinical indication. Study 
medication will then be dispensed with instructions to take 18-24 hours prior to scheduled 
pre-operative visit. All women will receive a diary to collect side effect information.  
Day 2: Pre-operative visit 
Women will return for their scheduled pre-operative visit the day prior to their scheduled 
procedure. Diaries will be collected and reviewed and osmotic dilators (Dilapan-S 4-mm) will 
be placed. Pain score measured by VAS will be collected at time of dilator placement. 
Day 3: Standard dilation and evacuation procedure 


Participants will proceed to the operating room and undergo sedation per anesthesia 
guidelines. Initial cervical dilation using Pratt dilators will be measured after dilator removal. 
Standard dilation and evacuation will be performed.  
 
1.1.6 
Follow-up procedure 
There will be no follow-up necessary and the end of the procedure will indicate study 
completion. 
1.1.7 
Criteria for discontinuation 
Women who report not taking the study medication will be discontinued from the study. 
Participants may discontinue from the study for any reason. 
1.1.8 
Laboratory and other investigations 
Not applicable 
1.1.9 
Data management 
Each participant will be assigned a file in a locked cabinet of a locked office. Participant files 
will contain signed consent forms, study allocation number, and paper copies of data 
collection forms.  
1.1.10 Data analysis 
As the primary outcome is a dichotomous variable, I will perform logistic regression 
analyses. The number of cervical dilators will be collected either at time of clinic visit or by 
chart review. Missing data will be minimized by allowing for exclusion of any potential 
participant who may be judged to have increased risk for loss to follow up at time of 
enrollment and prior to randomization. We will include all women randomized and perform 
intent-to-treat analysis with no apparent exclusions. In addition, a second analysis will be 
conducted excluding women who do not report ingesting the study medication.  


 
At time of enrollment, we plan to collect baseline demographic data, including age, race, 
ethnicity, education level, obstetric history, and history of cervical procedures. I will perform 
univariate analyses to compare the two study groups at baseline. If any variables are 
significantly different, I will utilize those variables to adjust the logistic regression for the 
primary outcome. While not powered to detect a statistically significant difference among 
the two groups for the secondary outcomes, exploratory analyses will be performed to 
identify possible trends and areas of interest for a subsequent larger trial. The data analysis 
will be as follows: 
Secondary outcome 
Data analysis plan 
Proportion of appropriate number of dilators 
Logistic regression 
Cervical dilation at time of procedure 
Linear regression 
Number of tablets of ibuprofen and Tylenol #3 utilized with dilators 
in place 
Logistic regression 
Proportion of women requiring mechanical dilation at time of 
procedure 
Logistic regression 
Pain at time of dilator placement (VAS) 
Linear regression 
Provider perception of overall ease of procedure 
Provider perception of difficulty in dilating the cervix when required 
Logistic regression 
Overall complication and adverse event rate 
Logistic regression 
 
  
1.1.11 Number of subjects and statistical power 
 
Control group 


 
% with +2 
dilators 
1 
5 
10 
15 
20 
Study group 
10 
242 
950 
-- 
-- 
-- 
20 
100 
176 
438 
1864 
-- 
30 
60 
86 
144 
268 
632 
35 
50 
68 
102 
166 
304 
40 
42 
54 
76 
114 
182 
45 
36 
44 
60 
84 
124 
50 
30 
38 
50 
66 
90 
60 
24 
28 
34 
44 
56 
70 
18 
22 
26 
30 
38 
80 
14 
16 
20 
22 
26 
 
The appropriate number of dilators is based on gestational age at this university:  
a. 20 weeks 0 days to 20 weeks 6 days: at least 5 dilators  
b. 21 weeks 0 days to 21 weeks 6 days: at least 6 dilators 
c. 22 weeks 0 days to 23 weeks 6 days: at least 7 dilators 
Without adjunctive medications, it is assumed that placing two more than the standard 
number of dilators will be difficult and a rare occurrence in about 10% of women. With 
adjunctive preparation with mifepristone, dilator placement will lead to an increased 
proportion of women (45%) receiving two additional dilators than the indicated number. We 
require 60 participants to detect a difference of 35% between the two groups and maintain 
80% power and an alpha of 0.05. To account for medication nonadherence, we plan to 
recruit 10% more patients for a total of 66 women.