Early Amniotomy Following Transcervical Foley Balloon in the Induction of Labor: a Randomized Clinical Trial
Phase: NA
Conditions: Labor Induction, Early Amniotomy
Sponsor: The University of Texas Medical Branch, Galveston

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Title: Early amniotomy following transcervical Foley balloon in the induction of labor: a randomized 
clinical trial 
 
NCT#: 04573517 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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The University of Texas Medical Branch at Galveston  
 
Research Protocol IRB #20-0163 
 
 
Title: Early amniotomy following transcervical Foley balloon in the induction of labor: a randomized 
clinical trial 
 
Principal Investigator: Marissa Berry, MD 
 
Collaborators: Amanda Wang, MD, Corrie Degraffenreid, MD, Yihharn Hwang, MD, Christopher 
Moutos, MD, Daphne Arena Goncharov, MD, Jacey Beasley, MD, Rachel Dillard, MD, Kelly Lamiman, 
MD, Jennifer Rogers, MD, Megan Slan, Xue Zhang, MD 
 
Faculty supervisor: Antonio Saad, MD 
 
Funding: Departmental 
 
1. Introduction and Purpose: 
Amniotomy is a common practice in the management of labor induction. It is performed using a plastic 
hooked device to rupture the amniotic membranes. Currently at UTMB, it is left to the discretion of the 
provider to determine when amniotomy is performed during labor. There is little data to guide the timing 
of amniotomy. A recent meta-analysis suggests that amniotomy performed earlier in the labor course is 
associated with a decreased time from induction to delivery, with no change in rates of cesarean section1. 
However, one study showed longer labors with an increase in rates of cesarean section with early 
amniotomy2. Additionally, this meta-analysis was limited by the small number of trials included with 
varying methods of cervical ripening used prior to amniotomy, including Foley balloon, prostaglandins, 
or a combination2,3,4,5. Lastly, in two of the studies included, spontaneous rupture of membranes was used 
as the control group, which does not provide clear guidance regarding the timing of amniotomy during 
labor, as in many cases amniotomy was not performed4,5. Further data is needed to sufficiently evaluate 
the timing of amniotomy during induction, controlling for the method of cervical ripening. 
 
The purpose of this study is to evaluate the impact of early versus delayed amniotomy on time from 
induction to the active phase of labor, as well on total time to delivery and maternal and neonatal 
outcomes in women undergoing cervical ripening with the Foley balloon.  
 
2. Background:  
Amniotomy, i.e. artificial rupture of amniotic membranes, has become a common method used in 
management of both induction and augmentation of labor. It has been shown to shorten the duration of 
labor6. Risks associated with amniotomy include ascending infection, fetal heart rate decelerations, 
umbilical cord prolapse, and rupture of vasa previa6. While there are risks associated with amniotomy, 
there are also risks associated with prolonged labor, including an association with cesarean delivery and 
decreased fetal cord pH6.  
 
Timing of amniotomy in the management of induction of labor has not been widely studied. The limited 
studies have mixed results, but a recent meta-analysis suggests that early amniotomy shortens the length 

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of labor and has no effect on rates of cesarean section1,3,4,5. However, these studies use a variety of 
methods for cervical ripening prior to amniotomy, which may affect the outcome as well. Additionally, 
the studies differed in whether they compared early amniotomy to delayed amniotomy or spontaneous 
rupture of membranes. Levy et al. showed longer labors with increased cesarean section rates in those 
receiving early amniotomy after cervical ripening with a Foley balloon2. These results may be in part due 
to the fact that oxytocin infusion was not initiated in these subjects until the labor progress was deemed to 
be inadequate.  
 
With the limited amount of published research, and conflicting results, more data is needed to be able to 
determine the ideal time for amniotomy during the management of the induction of labor, specifically 
when using a Foley balloon for cervical ripening.   
 
The primary objectives of this study are to evaluate time to reach active phase of labor (defined as 6 cm or 
more of cervical dilation). The secondary objectives of this study are to evaluate in these subjects 1) 
cesarean section rates and indications, 2) occurrence of maternal complications including isolated 
maternal fever, chorioamnionitis, postpartum hemorrhage, endometritis, wound infection, and 3) 
occurrence of neonatal complications including umbilical cord prolapse, Apgar score <7 at 1 and 5 
minutes, cord pH <7.0, NICU admission, neonatal infection. We will also be looking at time to vaginal 
delivery and vaginal deliveries within 24, 36 and 48 hours. 
 
3. Concise Summary of Project: 
• 
The target population for our study is both nulliparous and parous women who present for 
induction of labor. If there is a decision by the obstetric team to place a transcervical Foley 
balloon for cervical ripening, the obstetric team will notify the research team so that the patient 
may be screened for the study. If the subject consents to participation, written informed consent 
will be obtained by person-to-person contact. The PI or a collaborator will be responsible for the 
informed consent. After informed consent is obtained, the transcervical Foley balloon will be 
placed. The method of placement will be left to the discretion of the provider. After placement of 
the Foley balloon, the subject will be randomized to the study group (early amniotomy) or the 
control group (delayed amniotomy). 
 
The control group will undergo amniotomy at least four hours after expulsion of the Foley 
balloon. 
 
The study group will undergo amniotomy as soon as possible after Foley balloon expulsion or 
within two hours of expulsion. 
 
At any point, if the treating provider determines amniotomy is unsafe, amniotomy may be 
delayed and performed as soon as the provider deems safe.  
 
This will be an unblinded randomized clinical trial. 
 
No significant adverse effects are expected with the use of amniotomy. The most significant risks 
associated with amniotomy are fetal heart rate decelerations, ascending infection, umbilical cord 
prolapse (<1%), rupture of vasa previa (<1%). The subject will undergo inpatient induction of 
labor, so any adverse reaction would be promptly detected and addressed. 
 
• 
The number of subjects studied will be 174 subjects at UTMB. 
The subjects will be withdrawn from the study if she wishes to discontinue participation. If any of 
the exclusion criteria listed above are met, or there is a change in condition that leads to inclusion 

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criteria no longer being met, data collection will be terminated and the subject will be withdrawn 
from the study.  
 
4. Study Procedures 
The decision to place a transcervical Foley balloon as a means of mechanical dilation will be made by the 
managing clinical team independent of the trial. After a subject who meets inclusion criteria agrees to be 
screened for participation in our study, the obstetric team will contact one of the investigators. Signed 
informed consent will be obtained by the PI or collaborator. Intrapartum management will be performed 
by the obstetric team. Providers will only be performing activities that are standard of care, but will 
receive protocol training. Documentation of provider training will be maintained with the research records 
as a training log dated and signed. The total participation time in the study will be considered terminated 
at time of delivery. 
 
The data collected will be kept on a password-secured UTMB computer. An encrypted USB flash drive 
will be used to transfer data. The data will be linked to the subject by the subject's MRN number. This 
identifier is needed to access and analyze demographic data. During analysis of the data, all identifiers 
will be deleted. 
 
 
4.1 Screening, Recruitment, and Consenting: 
• 
Under the direction of the PI, trained research staff will be available 24/7 to screen and consent 
subjects according to study protocol. Subjects will be enrolled at the time a decision to place a 
transcervical Foley balloon for purposes of mechanical dilation is made in labor and delivery. 
Potential subjects will be approached for recruitment at least 30 minutes prior to Foley balloon 
placement in order to ensure adequate time to make an informed decision regarding their 
participation. 
• 
After informed consent is obtained, the subject will be randomized to the study group or the 
control group. A screening log will be used to track all subjects approached for the study. 
Subjects will only be randomized on L&D after the transcervical Foley balloon has been placed 
AND they continue to be eligible.  
• 
Recruitment: We will recruit all pregnant patients admitted to L&D for induction of labor who 
have had a decision made by their managing clinical team to place a transcervical Foley balloon 
for purposes of mechanical dilation who do not meet any of the exclusion criteria listed above. 
Once the inclusion criteria for our study are met, the primary team will inform the patient about 
the study and ask her authorization to contact one of the study personnel. Eligible subjects may 
not be patients of the study providers; hence, in these cases, the managing clinical providers will 
inform eligible subjects for permission to research staff approach for potential recruitment. All 
clinical providers (residents, midwife and obstetricians) that work in the L&D unit will be 
educated by email and in person of the trial’s eligibility and purpose before initiation of the trial.  
• 
Consenting process: Written consent will be obtained by direct person-to-person contact. The 
principal investigator or a collaborator will be responsible for the informed consent. The consent 
form will be thoroughly reviewed with the subjects prior to signing. Questions will be invited and 
just prior to signing, the research staff will ask questions of the subject to ensure her complete 
understanding of the study and her voluntary willing participation.  
Subjects will be informed that their decision about participating in the study will in no way affect 
the care they will receive. Consent will be obtained prior to placement of the Foley balloon. Non-
English-speaking subjects are anticipated to be part of the study population and informed consent 
will be provided in their primary language. For non-English speaking subjects, a certified 
translator will review the consent with them. Additionally, the consent will be translated in 
Spanish.  

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Privacy will be maintained by approaching and consenting subjects in their private room in L&D.  
 
 
The data collected will not be used for clinical diagnosis or treatment purposes. 
 
Subjects will be reassured that participation in the study is voluntary and will not interfere with the 
diagnosis or treatment of her condition. 
 
The subjects will receive the same care and expertise as any other patient treated in our unit. 
 
Placement of the Foley balloon and amniotomy will be performed by the managing obstetrical team, that 
are trained physicians that perform these procedures in a daily schedule as part of their routine clinical 
skills and duties. 
 
4.2. Randomization and Masking 
A confidential computer-generated simple randomization scheme (using STATA 16, Dallas, TX) has 
been prepared. A randomization log with group assignment, subject name, and medical record number 
will be used to track the randomization process. 
 
Subjects will be randomized in a ratio of 1:1 for delayed or early amniotomy. 
 
Due to the nature of the intervention, blinding of subjects or providers will not be possible. 
 
The subject will be included in the analysis by intent-to-treat once the randomization assignment has been 
made. 
 
4.3. Amniotomy 
The control group will undergo delayed amniotomy. At least four hours after Foley balloon expulsion, the 
provider will perform amniotomy using a plastic amniotomy hook. After amniotomy, standard 
intrapartum management of the subject will ensue. 
 
The study group will undergo early amniotomy. The provider will perform amniotomy as soon as 
possible after Foley balloon expulsion or within two hours of expulsion. After amniotomy, standard 
intrapartum management of the subject will ensue. 
 
If the provider feels the amniotomy is unsafe (floating or ballotable presenting part, head not engaged in 
the pelvis), amniotomy will be performed as soon as it is deemed safe. If amniotomy is performed outside 
of the time limits outlined, the subject will remain in the study since we will perform an intent-to-treat 
analysis. 
 
Foley balloon placement is standard of care in our facility for cervical ripening. Decision for its 
placement will be solely left to provider’s discretion. Both groups will have a foley balloon placed as per 
standard protocol in our institution. 
 
Oxytocin infusion will be left to provider’s discretion based on our unit’s standard of practice. 
 
4.4. Baseline Procedures 
Routine intrapartum care will be provided by the subject’s managing obstetric team. 
 
Trained and experienced research staff will be responsible for all research data abstraction. 
 

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The PI and collaborators will review and validate the diagnosis for all subjects identified to have the 
primary outcomes. 
 
Maternal and neonatal outcomes will be assessed following delivery. 
 
Subjects will be encouraged to call the principal investigator with any concerns. 
 
Data collection forms will be used during these processes and charts will be reviewed up to 30 days 
postpartum. We will collect demographic data, as well as data related to the subject’s intrapartum course, 
delivery, and immediate postpartum period while inpatient. Data on newborn status, including those 
admitted to the NICU, will be obtained from the infants’ charts. 
 
Subjects’ participation will end after being discharged home from the hospital. 
  
4.5. Study visits / Follow-up  
No additional postpartum follow-up visits will be performed. 
 
4.6. Withdrawals 
Subjects who withdraw from the study after randomization will be excluded from further follow-up. 
Outcomes ascertained up until the time of withdrawal will be reported in intent-to-treat fashion.  
!
 

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Study Summary Flow Diagram 
!
 
Assessed for eligibility  
Excluded 
¨   Not meeting inclusion criteria 
¨   Declined to participate  
¨   Other reasons  
The PI will review and validate the diagnosis 
for all subjects identified to have the primary 
outcomes. 
Outcomes will be assessed by chart review 
following delivery. 
Allocated to Control Arm 
¨  Delayed amniotomy 
-
Amniotomy will be performed > 4 hours 
after Foley balloon expulsion 
Outcomes will be assessed by chart review 
following delivery. 
Allocated to Experimental Arm 
¨  Early amniotomy 
-
Amniotomy will be performed within 2 
hours of Foley balloon expulsion 
The PI will review and validate the diagnosis 
for all subjects identified to have the primary 
outcomes. 
Allocation 
Analysis 
Follow-Up 
Randomized 
Enrollment on L&D 
Informed consent obtained 

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4.9. Primary Outcomes 
• Time interval from Foley balloon placement to reaching the active phase of labor (6 cm 
cervical dilation) 
 
4.10 Secondary Outcomes 
• Induction to delivery time in minutes 
• Time interval from completion of cervical ripening to delivery in minutes 
• Vaginal delivery within 24, 36 and 48 hours of induction 
• Cesarean section rates and indications 
• Operative delivery rates 
• Total length of hospital stay 
• Maternal outcomes 
o Isolated maternal fever 
" Chorioamnionitis (also known at “IAI,” or “triple I”): 
# A presumptive diagnosis of IAI (suspected triple I) can be made in 
women with: 
• Fever – ≥39.0°C [102.2°F] or 38.0°C [100.4°F] to 38.9°C 
[102.02°F] on two occasions 30 minutes apart, without another 
clear source PLUS one or more of the following [1]: 
• Baseline fetal heart rate >160 beats/min for ≥10 minutes, excluding 
accelerations, decelerations, and periods of marked variability 
• Maternal white cell count >15,000/mm3 in the absence of 
corticosteroids and ideally showing a left shift (bandemia) 
• Purulent-appearing fluid coming from the cervical os visualized by 
speculum examination 
# A confirmed diagnosis of IAI can be made in women with: 
• All of the above PLUS one or more of the following objective 
laboratory findings: 
" Positive Gram stain of amniotic fluid 
" Low glucose level in amniotic fluid 
" Positive amniotic fluid culture 
" High white cell (WBC) count in amniotic fluid in the 
absence of a bloody tap 
" Histopathologic evidence of infection or inflammation or 
both in the placenta, fetal membranes, or the umbilical cord 
vessels (funisitis) 
" Endometritis - must meet the following criteria: 
# Infection occurs within 30 days after the operative procedure AND 
# Infection presumed to involve the uterus AND 
# Subject has at least one of the following: 

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• Purulent drainage from a drain that is placed through a stab wound 
into the abdomen or pelvis 
• Organisms isolated from an aseptically-obtained culture of fluid or 
tissue in the organ / space 
o Postpartum hemorrhage 
§ EBL >1000 cc 
o Wound infection 
o Umbilical cord prolapse 
 
• Neonatal outcomes 
o Apgar score <7 at 1 and 5 minutes 
o Cord arterial pH <7.0 
o NICU admission 
o Neonatal infection, defined as sepsis, fever, positive cultures, or a suspicious 
clinical course that warranted treatment with antibiotics 
 
5. Sub-Study Procedures:  No sub-studies will be performed 
 
6. Criteria for Inclusion of Subjects 
• Age ³ 18 
• Singleton pregnancy 
• Term gestation (³37 weeks gestation) 
• Cephalic presentation 
• Undergoing labor induction with transcervical Foley balloon 
 
7. Criteria for Exclusion of Subjects 
• Previous uterine surgery 
• Prelabor rupture of membranes 
• Severe pre-eclampsia, HELLP, or eclampsia 
• HIV, HCV, or HBV 
• Heart disease 
• Fever (≥38 0C) at admission 
• Category II or III fetal heart rate tracing prior to randomization 
• Polyhydramnios 
• Fetal growth restriction <3% 
• EFW > 4200 g 
• Fetal demise or major congenital anomaly 
• Prisoners 
 
8. Sources of Research Material: Electronic medical chart / records 
 
9. Potential Risks: 
 
9.1. Amniotomy & Randomization Risk 

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Since the timing of amniotomy will be randomized, it is possible that the subject may be in a 
group with higher adverse outcomes, such as early amniotomy. Risks with amniotomy including 
fetal heart rate decelerations, ascending infection, umbilical cord prolapse, and bleeding due to 
vasa previa, and it is possible to see a difference in the rates of these complications with earlier 
amniotomy.  
 
9.2. Loss of Confidentiality 
Any time information is collected, there is a potential risk for loss of confidentiality. Every effort 
will be made to keep subject’s information confidential; however, this cannot be guaranteed. 
 
10. Subject Safety, Data Monitoring and Protocol deviations 
Subjects will be continuously monitored throughout their labor course for the development of 
any adverse events. If a complication is identified, immediate treatment will ensure per standard 
of care. Study collaborators will be responsible for notifying the principal investigator of any 
adverse events. The PI and research collaborators will be responsible for monitoring the safety of 
this study. The PI will notify the faculty sponsor of the occurrence of any adverse events. The 
yearly report, submitted at time of continuing review, will include participant demographics, 
expected versus actual recruitment rates, summary of any quality assurance or regulatory issues, 
summary of adverse events (AEs) or serious adverse events (SAEs) which may have occurred, 
and any changes in the protocol as a result of these issues. 
 
The PI and collaborators will ensure all aspects of data quality including monitoring for 
adherence to consent procedures, inclusion and exclusion criteria, valid abstraction, correct 
entry, timeliness and responsiveness to data queries. The faculty sponsor will be notified by the 
PI if any issues are identified regarding data quality during the monitoring process. 
  
Data will be collected and stored with the participant ID code only. The master enrollment log 
linking patient identifiers with study ID numbers will be kept in a password-protected database 
on the OB/GYN department’s internal server separate from the data. Data collection forms will 
be used. Data on these forms devoid of personal identifiers will be securely stored at our 
perinatal research division. The PI will be available to monitor the data and correct any 
discrepancies based on source documents if needed. 
 
For each patient enrolled in the study, their primary obstetric care providers and team currently 
taking care of the patient will be notified of their participation in person after randomization. 
For any deviations from study group assignment that may arise, providers will be asked to notify 
the study team or if missed, the deviation will be identified chart review. The study team will 
then complete documentation which will be submitted to the IRB as a protocol deviation via 
InfoEd; according to IRB policies. 
 
11. Procedures to Maintain Confidentiality 
• The data collected will be indirectly linked to the subject by subject's MRN number.  
• When the subject accepts to participate in the study, a number will be attributed to the 
subject, and this number will be entered on the data collection sheet. 

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• The data collected will be transferred to the PI's password-secured UTMB computer that is 
stored in a locked room using an USB flash drive.  
• The study PI will be the only person to have a list with the number designated to each subject 
and the corresponding subject’s MRN number. This list will be kept in a locked cabinet of 
the PI's locked UTMB office. This identifier is needed to access and analyze demographic 
data. During analysis of the data, all identifiers will be deleted. 
• Data will not be disclosed to outside persons or entities. 
  
12. Potential Benefits 
Subjects who undergo either early or delayed amniotomy may be at decreased risk for adverse 
perinatal outcomes. If this is the case, our study stands to benefit women who have amniotomy in 
future cases of labor induction. 
 
13. Statistical Approach 
Analysis will be performed by intent to treat. Univariable and multivariable analysis will be used 
to describe the population in the study and to identify potential confounding variable.  For this 
analysis normality will be tested using Shapiro-Wilk method. Demographics and descriptive 
statistics such as t test, Pearson’s chi square, and Mann-Whitney tests will be used as indicated. 
Data will be either shown as median +/- Range or mean +/- SDEV.  Statistical analyses of 
primary and secondary outcomes between two groups will be performed by multivariate logistic 
regression analysis accounting for confounding variables if indicated. 
 
Based on our prior results (DILAFOL Trial), women who received Foley balloon and delayed 
amniotomy reached active phase of labor in 1111 mins with a standard deviation of 525 mins8. 
Using difference rate of 25%, power of 90% and 2-sided alpha of 0.05, we estimate that we will 
need 150 with complete ascertainment. This difference of 278 or ~4hours was decided after 
consulting clinical experts in the field of obstetrics, supporting clinical reasoning that a 
difference between both methods is clinically significant. Detailed from stata 16 : Estimated 
sample sizes for a two-sample means test (z test ) ;Study parameters: alpha =    0.0500; power =    
0.9000; delta = -278.0000;  mean1 = 1111.0000; mean2 =  833.0000 sd =  525.0000 Estimated 
sample sizes: N =       150 
 N per group =        75. Assuming a 13% loss to follow, we propose to enroll a total of 174 
subjects. Analyses will be performed by intent to treat. We will be using STATA 16 (Dallas, TX) 
for statistical computations 
This trial will be registered with Clinical Trials Register (Clinicaltrials.gov), before recruitment 
is initiated and after IRB approval. 
 
 
 
 
 
 
 
 
 
 

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References 
 
1. De Vivo V, Carbone L, Saccone G, Magoga G, De Vivo G, Locci M, et al. Early amniotomy 
after cervical ripening for induction of labor: a systematic review and meta-analysis of 
randomized controlled trials. Am J Obstet Gynecol 2020 
 
2. Levy R, Ferber A, Ben-Arie A, Paz B, Hazan Y, Blickstein I, et al. A randomized comparison 
of early versus late amniotomy following cervical ripening with a Foley balloon. BJOG 
2002;109:168-172 
 
3. Macones GA, Cahill A, Stamilion DM, Odibo AO. The efficacy of early amniotomy in 
nulliparous labor induction: a randomized controlled trial. Am J Obstet Gynecol 
2012;207:403.e1-5 
 
4. Makarem MH, Zahran KM, Abdellah MS, Karen MA. Early amniotomy after vaginal 
misoprostol for induction of labor: a randomized clinical trial. Arch Gynecol Obstet 
2013;288:261-265 
 
5. Bostanci E, Eser A, Abide CY, Kilicci C, Kucukbas M. Early amniotomy after dinoprostone 
insert used for the induction of labor: a randomized clinical trial. J Matern Fetal Neonatal Med 
2018;31:352-356 
 
6. Smyth R, Alldred SK, Markham C. Amniotomy for shortening spontaneous labor. Cochrane 
Database of Systematic Reviews 2013;1 
 
7. Spong CY, et al. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy 
Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal 
Medicine, and American College of Obstetricians and Gynecologists Workshop. Obstet Gynecol. 
2012 Nov;120(5):1181-93.   
8. Saad AF, Villarreal J, Eid J, Spencer N, Ellis V, Hankins GD, Saade GR. A randomized 
controlled trial of Dilapan-S vs Foley balloon for preinduction cervical ripening (DILAFOL 
trial). Am J Obstet Gynecol 2019;220(3):275.e1-275.e9