Outpatient Foley Catheter Compared to Usual Inpatient Care for Cervical Ripening: a Randomized Controlled Trial
Phase: NA
Conditions: Pregnancy
Sponsor: Mayo Clinic

 
 
 
 
 
 
 
Outpatient Foley Catheter 
Compared to Usual Inpatient 
Care for Cervical Ripening: A 
Non-Randomized Prospective 
Study 
NCT02546193 
November 16, 2016 

Outpatient vs. inpatient cervical ripening  
 
Version 1.9 
 
  
OUTPATIENT FOLEY CATHETER COMPARED TO USUAL 
INPATIENT CARE FOR CERVICAL RIPENING: A NON-
RANDOMIZED PROSPECTIVE STUDY 
 
 
 
 
 
Regulatory Sponsor: 
Dr. Vanessa Torbenson  
Department of Obstetrics and Gynecology  
200 First Street Southwest  
Rochester, MN 55905  
507-266-9873  
Funding Sponsor: 
 
Obstetrics and Gynecology Research Committee  
200 First Street Southwest 
Rochester, MN 55905 
507-266-7712 
 
Obstetrics and Gynecology Education Committee  
200 First Street Southwest  
Rochester, MN 55905  
507-266-3262 
 
Study Product: 
Transcervical single balloon Foley catheter 
Protocol Number: (IRBe) 
 
 
14-008988 
  
 
IND Number: 
Not applicable  
 
 
 
 
 
Initial version: 7/6/15 Version (1.1)  
Modification 4 11/20/2015 Version (1.6) 
Modification 5  2-15-16 Version (1.7) 
Modification 8, Change in PI, 4-28-16 Version (1.8) 
Modification 9, Prospective study design Version (1.9) IRB approved 11-16-16 
 

Outpatient vs. inpatient cervical ripening  
 
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Table of Contents 
 
STUDY SUMMARY ...................................................................................................................................... 5 
1 
INTRODUCTION ................................................................................................................................. 6 
1.1 
BACKGROUND .................................................................................................................................... 6 
1.2 
INVESTIGATIONAL AGENT .................................................................................................................... 7 
1.3 
CLINICAL DATA TO DATE..................................................................................................................... 7 
1.4 
DOSE RATIONALE AND RISK/BENEFITS .................................................................................................. 8 
2 
STUDY OBJECTIVES .......................................................................................................................... 8 
3 
STUDY DESIGN ................................................................................................................................... 9 
3.1 
GENERAL DESIGN ............................................................................................................................... 9 
3.2 
PRIMARY STUDY ENDPOINTS .............................................................................................................. 14 
3.3 
SECONDARY STUDY ENDPOINTS ......................................................................................................... 14 
3.4 
PRIMARY SAFETY ENDPOINTS ............................................................................................................ 16 
4 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL ...................................................... 16 
4.1 
INCLUSION CRITERIA ......................................................................................................................... 16 
4.2 
EXCLUSION CRITERIA ........................................................................................................................ 17 
4.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING ....................... ERROR! BOOKMARK NOT DEFINED. 
4.4 
EARLY WITHDRAWAL OF SUBJECTS .................................................................................................... 18 
4.4.1 
When and How to Withdraw Subjects ...................................................................................... 18 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects ............................................................ 19 
5 
STUDY DRUG .................................................................................................................................... 19 
5.1 
DESCRIPTION .................................................................................................................................... 19 
5.2 
TREATMENT REGIMEN ....................................................................................................................... 19 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ................................................................ 19 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ......................................................................... 19 
5.5 
SUBJECT COMPLIANCE MONITORING ................................................................................................... 19 
5.6 
PRIOR AND CONCOMITANT THERAPY .................................................................................................. 20 
5.7 
PACKAGING ...................................................................................................................................... 20 
5.8 
MASKING/BLINDING OF STUDY........................................................................................................... 20 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN ................................................................................. 20 
5.9.1 
Storage ................................................................................................................................. 20 
5.9.2 
Dispensing of Study Drug ....................................................................................................... 20 
5.9.3 
Return or Destruction of Study Drug ......................................... Error! Bookmark not defined. 
6 
STUDY PROCEDURES ...................................................................................................................... 20 
6.1 
CLINIC VISIT ..................................................................................................................................... 20 
6.2 
INITIAL ARRIVAL TO THE FAMILY BIRTH CENTER (BOTH GROUPS) .......................................................... 20 
6.3 
RETURN TO THE FAMILY BIRTH CENTER AFTER DISMISSAL HOME (INTERVENTION GROUP ONLY) ............... 21 
6.4 
INPATIENT POSTPARTUM STAY ............................................................................................................ 21 
6.5 
POSTPARTUM FOLLOW UP ................................................................................................................... 21 
7 
STATISTICAL PLAN ......................................................................................................................... 21 
7.1 
SAMPLE SIZE DETERMINATION ........................................................................................................... 21 
7.2 
STATISTICAL METHODS ..................................................................................................................... 22 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ............................................................................................. 23 
8 
SAFETY AND ADVERSE EVENTS ................................................................................................... 23 
8.1 
DEFINITIONS ..................................................................................................................................... 23 
8.2 
RECORDING OF ADVERSE EVENTS ....................................................................................................... 25 

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8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS .......................................... 25 
8.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB ........................................................... 25 
8.4 
UNMASKING/UNBLINDING PROCEDURES ............................................................................................. 26 
8.5 
MEDICAL MONITORING ..................................................................................................................... 26 
9 
DATA HANDLING AND RECORD KEEPING .................................................................................. 26 
9.1 
CONFIDENTIALITY ............................................................................................................................. 26 
9.2 
SOURCE DOCUMENTS ........................................................................................................................ 26 
9.3 
CASE REPORT FORMS ........................................................................................................................ 27 
9.4 
RECORDS RETENTION ........................................................................................................................ 27 
10 
STUDY MONITORING, AUDITING, AND INSPECTING ................................................................ 28 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 28 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 28 
11 
ETHICAL CONSIDERATIONS ......................................................................................................... 28 
12 
STUDY FINANCES ............................................................................................................................ 29 
12.1 
FUNDING SOURCE ......................................................................................................................... 29 
12.2 
CONFLICT OF INTEREST ................................................................................................................. 29 
13 
PUBLICATION PLAN ....................................................................................................................... 29 
14 
REFERENCES ................................................................................................................................... 29 
15 
ATTACHMENTS .................................................................... ERROR! BOOKMARK NOT DEFINED. 
 
 
 
 
 
 
 
 

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List of Abbreviations 
 
 
LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DSMB 
Data and Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
 
 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
 
 
 
 
   
 
 
 

Outpatient vs. inpatient cervical ripening  
 
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Study Summary 
Title 
Outpatient Foley catheter compared to usual inpatient care for cervical 
ripening: A non-randomized prospective study  
Running Title 
Outpatient vs. inpatient cervical ripening  
Protocol Number 
14-008988 
Phase 
Pivotal 
Methodology 
Prospective 
Overall Study 
Duration 
24 months  
Subject Participation 
Duration 
4-36 hours  
Single or Multi-Site  
Single site  
Objectives 
To compare the length of pre-delivery hospitalization in pregnant 
women undergoing cervical ripening with a Foley catheter in the 
outpatient setting compared with standard methods administered in the 
inpatient setting.  
Number of Subjects 
40 Outpatient Foley Subjects + 160 standard of care subjects 
Total of 400 women and their babies 
Diagnosis and Main 
Inclusion Criteria 
Pregnant women at ≥ 37 weeks gestation who are scheduled for 
induction of labor and who have an unfavorable cervical exam (Bishop 
score <9 and cervical dilation <3cm) 
Study Product, Dose, 
Route, Regimen 
The Foley catheter is a single balloon catheter that is placed 
transcervically by a provider and inflated with 60cc of normal saline. It 
mechanically dilates the cervix to 3-4cm over several hours.   
Duration of 
Administration 
The device will remain in place until it passes through the cervix, 
generally when the cervix is dilated to 3-4 cm, which typically occurs 3-
12 hours after placement.   
Reference therapy 
Cervical ripening in the inpatient setting with either a Foley catheter 
and/or vaginal misoprostol 25 mcg tablets every 4 hours.  
Statistical 
Methodology 
The mean time of pre-delivery hospitalization between outpatient Foley 
catheter and inpatient usual care groups will be compared using a two 
sample t-test or the nonparametric equivalent Wilcoxon rank sum test.  
Secondary endpoints will be compared using two sample t-tests or the 
nonparametric equivalent Wilcoxon rank sum test for continuous 
endpoints or the chi-Square or Fisher’s exact test for categorical 
endpoints.  
 
 

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1 Introduction 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the procedures described in this protocol, applicable United States government 
regulations, and Mayo Clinic policies and procedures.  
 
1.1 
Background 
In 2012, 23% of pregnant women underwent induction of labor in the United States [1].  
Induction of labor is the use of pharmacologic and/or mechanical methods to initiate labor [2]. 
Cervical ripening generally refers to the early part of labor induction in cases where methods are 
required to achieve a “favorable cervix,” variably defined at ≥6 or ≥8 by Bishop score (a scoring 
system based on 5 components including cervical dilation, effacement, position, consistency, and 
fetal station with a range of 0-13) [3]. Cervical ripening in women with unfavorable cervical 
examinations has been shown to decrease cesarean delivery compared with oxytocin alone [4].  
Vaginal prostaglandins and the transcervical catheter are the two most common methods of 
cervical ripening. Cervical ripening can be a lengthy process, though often a passive one 
requiring little provider intervention.  It is conventionally performed in an inpatient setting; 
however, there has been an increasing amount of research investigating cervical ripening in the 
outpatient setting [5]. Although cervical ripening has traditionally been performed in the 
inpatient setting, the medical necessity of this practice is unproven [6].  Increasing the time a 
woman spends in her home environment has the potential to decrease the length of hospital stay 
and associated healthcare costs as well as improve maternal satisfaction.   
A recently published study comparing inpatient versus outpatient cervical ripening with 
vaginal prostaglandin E2 gel found no difference in clinical outcomes including oxytocin use, 
cesarean delivery, and vaginal delivery within 24 hours [6].  Importantly, though, women in the 
outpatient group were more likely to have tachysystole (more than 5 contractions in 10 minutes) 
with fetal heart rate changes, and less than half remained at home overnight.  The authors state, 
and we agree, that prostaglandins may not be the safest agent for outpatient cervical ripening.  
Compared to prostaglandins, the Foley catheter is associated with a decreased rate of uterine 
tachysystole with fetal heart rate changes [7]. There is no difference in the rate of 
chorioamnionitis, endometritis, undelivered women at 24 hours, meconium passage, or serious 
maternal or neonatal morbidity [7]. The Foley catheter has been shown to be comparable to 
prostaglandins with regard to cesarean delivery rates [8].  Thus, because the Foley catheter does 
not cause tachysystole with fetal heart rate changes and does not require interval dosing, it is a 
potentially promising option for outpatient cervical ripening.   
 
A recent retrospective review of 1,905 low risk women undergoing cervical ripening with 
the Foley catheter examined adverse effects occurring in the first 12 hours after Foley placement 
[9].  Of the 1,905 women studied, only 3 underwent cesarean delivery following Foley 
placement and post-placement monitoring (1 for face presentation and 2 for arrest of dilation). 
All 3 women would have been excluded from an outpatient trial based on rupture of membranes 
or spontaneous labor at the time of Foley placement. There were no stillbirths and no cesareans 
performed for abruption or nonreassuring fetal heart tracing.  Based on this study, the Foley 
catheter is a safe method of cervical ripening with no reported adverse fetal or maternal effects 
and should be considered for use in the outpatient setting.   

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Sciscione et al. performed the first prospective randomized controlled trial comparing the 
use of a Foley catheter in the inpatient versus outpatient setting [10]. A total of 111 women were 
enrolled; 61 were randomized to the outpatient setting. All women had a number 16 Foley 
catheter filled with 30cc of sterile saline placed by sterile speculum exam. The primary outcome 
was difference in Bishop score from the first cervical exam to the cervical exam the next 
morning. They found no significant difference in the change in Bishop score, pain scores, or total 
induction time between the groups. The inpatient admission time was 9.6 hours longer in the 
inpatient group compared to the outpatient group. Only 8% (n=5) returned overnight for either 
rupture of membranes or labor.   
 
A similar, more recent trial by Henry et al. compared outpatient Foley catheter placement 
to inpatient PGE2 vaginal gel in 101 women [11]. The outpatient group spent 11.1 fewer hours in 
the hospital prior to delivery compared to the inpatient group (p<.001). They also felt less pain 
and got more sleep during cervical ripening. Oxytocin was required for induction more often in 
the outpatient group. No adverse neonatal or maternal outcomes were associated with outpatient 
Foley catheter allocation. Only one woman in the outpatient group returned to the hospital earlier 
than scheduled (for regular, painful contractions). 
 
The trials by Sciscione et al. and Henry et al. have limitations, though. First, neither 
utilized a standard protocol for labor induction. Second, the inpatient control group was allocated 
to either Foley usage alone (Sciscione et al.) or prostaglandin PGE2 gel alone (Henry et al.). We 
believe the most appropriate comparison group is “usual care” wherein women may receive 
either the Foley catheter or prostaglandins based on patient and provider preference.  
The use of a Foley catheter for cervical ripening in the outpatient setting has the potential 
for substantial advancement to the induction process for the patient, provider, and healthcare 
system. The Foley catheter is a safe, inexpensive method of cervical ripening that causes less 
fetal heart rate effects than other ripening methods [7, 8]. Women may find gratification by being 
in their home environment during more of their labor course [12]. Providers and healthcare 
systems may be better able to allocate their resources with decreased length of stay during the 
early induction phase. A 2013 Cochrane review of outpatient cervical ripening concluded that 
more studies are required to demonstrate its efficacy and safety in this setting [5]. Our study will 
provide additional evidence of safety and efficacy to transition cervical ripening to the outpatient 
setting.     
 
1.2 
Investigational Agent 
The Foley catheter is a device used to achieve cervical ripening to start labor induction. It is the 
most common mechanical method used for cervical ripening in the third trimester. It is a single 
balloon catheter placed transcervically by a provider, either digitally or using a speculum for 
visualization. The balloon is placed above the internal os but below the fetal head, amniotic 
membranes, and placenta and is inflated with 30-80 mL of normal saline. Traction is placed on 
the catheter, either by taping the catheter to the patient’s thigh and/or intermittently by a 
provider. Over several hours, the balloon gradually dilates the cervix. The catheter is expulsed 
when the cervix is 3-4 centimeters. At this dilation, oxytocin (Pitocin) is much more effective.   
1.3 
Clinical Data to Date 
Please refer to section 1.1 and 1.2.  
 
  

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1.4 
Dose Rationale and Risk/Benefits 
Only one Foley catheter is placed during a patient’s labor induction course. The single balloon 
can be filled with 30-80 mL of normal saline. Our equipment best facilitates 30-60 mL. A study 
by Delaney et al. demonstrated that inflation with 60 mL increased the likelihood of delivery 
within 12 hours compared to 30 mL without any adverse maternal or neonatal outcomes [13]. 
Therefore, 60 mL was elected for this study.  
 
 
Common adverse effects of transcervical Foley catheters include discomfort and vaginal 
spotting. The patient may feel uncomfortable during placement of the Foley catheter and while 
the Foley catheter is in place. Similarly, women in the inpatient group can expect discomfort 
during the initiation of their labor induction as well, whether with the Foley catheter or vaginal 
misoprostol. Pain control options as described elsewhere in this document will be available for 
patient comfort. Available data suggests that the Foley catheter is tolerable from a pain 
perspective. Pennell and colleagues evaluated pain associated with the Foley catheter and found 
that pain with insertion was rated as 4/10 and pain during cervical ripening was 2/10 [14]. 
Overall satisfaction with induction of labor for Foley catheter was 8/10, which was equivalent to 
the other cervical ripening agents studied. 
Patients may also commonly experience vaginal spotting after placement of a Foley 
catheter. This is typically from cervical manipulation rather than clinically significant placental 
abruption. In the majority of cases, these etiologies can be distinguished by experienced clinical 
evaluations. If there is suspicion that vaginal bleeding represents placental abruption, the patient 
will be excluded from the trial and kept in the inpatient setting until delivery. The amount of 
blood lost from vaginal spotting is not clinically significant and is common during induction of 
labor in the inpatient setting.  
Less likely risks include the following: artificial or spontaneous rupture of membranes, 
initiation of spontaneous labor, and placental abruption, both clinically significant and 
insignificant. The patient will be educated regarding these risks. Should any of these events be 
diagnosed while the patient is in the Family Birth Center for post Foley monitoring, she will kept 
as an inpatient until delivery and excluded from the trial. Should any of these occur at home, the 
patient will return immediately to the Family Birth Center as outlined in both verbal and written 
instructions.  
2 Study Objectives 
2.1 Primary Objective 
The primary objective of the study is to compare the mean length of pre-delivery hospitalization 
among women undergoing induction of labor with a Foley catheter in the outpatient setting as 
compared to usual care in the inpatient setting.   
 
2.2 Secondary Objective 
Our secondary objectives are as follows: 
1) To compare the cesarean delivery rate among women undergoing outpatient Foley 
versus inpatient cervical ripening.  
2) To compare other maternal outcomes including: postpartum hemorrhage, infection, 
hospital readmission, and satisfaction with the induction process. 
3) To compare neonatal outcomes including: APGAR scores, umbilical artery pH, and 
nursery disposition. 

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3 Study Design 
3.1 
General Design 
The study began as a randomized control trial. The intervention group was comprised of low risk 
pregnant women who had a Foley catheter placed followed by dismissal home with return in 
approximately 12 hours for continuation of the labor induction process. The control group 
consisted of women who remained inpatient during the entire cervical ripening phase followed 
by continuation of the labor induction process in the inpatient setting.   
Due to difficulty enrolling women for the randomized control trial, a prospective design with an 
outpatient intervention group (Foley catheter) and matched inpatient control comparison group is 
proposed. Low risk pregnant women will be invited to participate in an outpatient Foley catheter 
intervention to begin their induction of labor process. Maternal/Neonatal outcomes and maternal 
satisfaction with the induction experience will be assessed. The comparison group will be 
enrolled to participate in the study in a limited way, providing responses to a maternal 
satisfaction of induction survey and allowing their and their baby’s electronic medical record to 
be followed for maternal/neonatal health outcomes and total hospital time. 
 
I. 
Enrollment of participants (Randomized Control Trial) 
A. Clinic nurses, clinical assistants who room patients, and the patient’s obstetric provider 
will refer eligible patients to the research coordinator.  
B. The Co-PI (Dr. Joy Beissel) will monitor the induction scheduling book in the Family 
Birth Center two weeks in advance to identify patients who may be eligible for the study. 
She will communicate the patient’s next clinic appointment to the research coordinators 
so these patients can be approached in clinic.   
C. Patients who receive their care in Mayo Clinic Family Medicine clinics will be eligible 
for this study. Their providers will be educated regarding this trial.  
II. 
Patient education, consent, and randomization 
A. The patients will be educated about induction of labor, the Foley catheter, and the 
proposed research study.  
1. 
The patient will be approached for this education during their last or 
second to last clinic visit before planned induction of labor.  
2. 
The education will be performed by a trained research coordinator, 
Principal Investigator, Co-Principal Investigator, or authorized obstetric provider.  
B. If the patient elects participation, she will undergo informed consent at that time.  
1. 
Informed consent will be obtained by a trained research coordinator, 
Principal Investigator, Co-Principal Investigator, or authorized obstetric provider. 
C. Randomization  
1. 
Randomization will occur the day before the planned induction to decrease 
drop out (for example: from spontaneous labor between the clinic visit and 
planned induction).  
2. 
The randomization will be computer generated.  
3. 
The patient’s randomization status will be accessed by the research 
coordinator. 
4. 
The research coordinator will contact the patient by phone to inform her of 
her randomization group.  
 

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5. 
Randomization will be stratified by parity (primiparous vs. multiparous) 
and by body mass index (current body mass index <30 kg/m2 vs. ≥30 kg/m2).    
 
III. 
Enrollment of participants (Prospective Study) 
A. Enrollment of outpatient intervention participants 
1. 
Clinic nurses, clinical assistants who room patients and the patient’s 
obstetric provider will refer eligible patients to the research coordinator.  
2. 
The study coordinator will screen the induction scheduling book in the 
Family Birth Center weekly to identify patients who may be eligible for the study. 
She will communicate with eligible women by telephone share general 
information about the study. If women are interested in learning more, she will 
meet with them at the patient’s next clinic appointment.  
3. 
Patients who receive their care in Mayo Clinic Family Medicine clinics 
will be eligible for this study. Their providers will be educated regarding this 
study. These women will be enrolled in the same manner as women from the 
antenatal clinic. 
(a) 
Patient education and consent 
(a) 
The patients will be educated about induction of 
labor, the Foley catheter, and the proposed research study.  
(b) 
If the patient elects participation, she will undergo 
informed consent at that time by a trained research study 
coordinator, Principal Investigator, Co-Principal 
Investigator, or authorized obstetric provider. 
(c) 
Parity (primiparous vs. multiparous) and BMI 
(current body mass index <30 kg/m2 vs. ≥30 kg/m2 ) will be 
recorded based on the stratification used in the Randomized 
Control Trial design.  
B. Enrollment of inpatient comparison (usual care) participants 
1. 
Women who decline participation in the outpatient intervention study may 
be approached to participate in a limited way as inpatient comparison control 
participants. 
2. 
The study coordinator will screen the OB White Board daily in the Family 
Birth Center to identify patients presenting for induction of labor who may be 
eligible for the study, but not captured during the weekly screening process. 
Eligible women will be approached, after discussion with their attending obstetric 
provider, to participate in the study as inpatient comparison usual care 
participants. 
3. 
Four inpatient comparison control participants will be enrolled with the 
same parity and BMI strata for every outpatient intervention patient enrolled (see 
III. A. 3. c. above). 
(a) 
Patient education and consent 
(a) 
The patients will be educated the proposed research 
study.  
(b) 
If the patient elects participation, she will undergo 
informed consent at that time by a trained research study 

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coordinator, Principal Investigator, Co-Principal 
Investigator, or authorized obstetric provider. 
 
IV. 
Protocol for the intervention group (Both Randomized Control Trial and Prospective 
Study) 
A. The patient will present to the Family Birth Center at 0730 or 1930.  
B. A nonstress test (NST) will be performed 
1. 
The fetal heart rate (FHR) is observed by external monitoring for at least 
20 minutes. The FHR is observed for the presence of accelerations, at least 2 in 40 
minutes that peak at least 15 beats per minute above the baseline and last for at 
least 15 seconds. The absence of at least 2 accelerations in up to 40 minutes is 
considered nonreactive.  
2. 
A nonreactive NST, the presence of ≥ 3 variable decelerations in a 20 
minute period, late-appearing decelerations, or any deceleration lasting ≥1 minute 
should be considered criteria for exclusion.  
C. An ultrasound will be performed for fetal presentation and amniotic fluid index.   
D. A cervical exam will be performed with calculation of a Bishop score.     
E. The patient will be asked the following standard questions. 
1. 
Are you experiencing any of the following: regular, painful contractions? 
Decreased fetal movement? Vaginal bleeding? Leakage of fluid from the vagina 
concerning for rupture of membranes? Fevers or chills?  
2. 
She will be excluded from the trial based on her answers, as described in 
section 4.2 “Exclusion Criteria.”  
F. A Foley catheter will be placed if the following criteria have been met: the nonstress test 
is reactive, the fetal presentation is cephalic, the amniotic fluid index is 5 centimeters or 
more, the Bishop score is <9, the cervical dilation is <3 cm, and she has no other clinical 
characteristics that exclude her from the trial.  
G. An obstetric provider will place a 16 French Foley catheter through the internal os. The 
balloon will be inflated with 60cc of normal saline. The distal end of the Foley will be 
taped to the patient’s inner thigh.  
H. The fetal heart rate tracing will be monitored for 1 hour after Foley placement. 
I. 
The patient will be sent home if the following criteria are met: the fetal heart rate tracing 
is reactive and category I; there is no evidence of rupture of membranes, spontaneous 
labor, or vaginal bleeding more than spotting; and maternal vital signs are within normal 
range.  
J. 
Pain control options 
1. 
While the Foley catheter is in place, the patient can use the following non 
pharmacologic methods to decrease discomfort: warm baths, massage, frequent 
position changes in a comfortable environment, relaxation techniques, and gentle 
stretching 
2. 
Pharmacologic methods available to the patient include:  
(a) 
Tylenol 1000mg orally q6 hours as needed for pain 
(b) 
Morphine 10 mg IM  once prior to dismissal 
K.  The patient will be instructed to return to the Family Birth Center approximately 12 
hours following their Foley bulb placement.  
L. The patient will be given verbal and written instructions as follows:  

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1. 
To return immediately to the Family Birth Center if she feels decreased 
fetal movement, if she is concerned her membranes ruptured, if she has vaginal 
bleeding more than spotting, if she has regular, painful contractions, if she has 
severe pain, if she develops a fever of ≥100.4F or ≥38.0 C, or if she develops any 
symptoms concerning to her.  
2. 
If the Foley catheter is expulsed at home, she is to record the time of 
expulsion. She does not need to return to the Family Birth Center earlier than 
planned due to expulsion.  
3. 
She will be provided with the 24 hour direct access line for the Family 
Birth Center to call with any questions or concerns.  
M. On arrival to the Family Birth Center at 12 hours later, the induction will be 
continued.  
1. 
The providing team will decide to proceed with oxytocin and/or artificial 
rupture of membranes. 
2. 
The oxytocin dose will be increased as determined by the Family Birth 
Center oxytocin low dose infusion regimen.  
3. 
The patient will have continuous electronic fetal monitoring.  
4. 
The remainder of her care during the first, second, and third stages of 
labor will be at the discretion of the providing team.   
5. 
If the Foley is still in place when the patient arrives, a provider should 
gently tug on it. If it does not come out, the providing team may choose to deflate 
and remove the Foley catheter (and then proceed with artificial rupture of 
membranes or oxytocin) OR leave the Foley in situ and place vaginal misoprostol. 
N. All patients’ labor progress will be monitored using a partogram.  Cesarean delivery 
will not be performed for arrest of labor or failed induction unless all criteria have 
been met as outlined by the Family Birth Center Workgroup protocol made effective 
6/2/14.   
  
V. 
Protocol for the control group (Randomized Control Trial) 
A. If the patient is in the outpatient control group, she will arrive to the Family Birth Center 
at a standard, predetermined time (typically 0730 or 1930) to undergo induction of labor.   
B. Method of cervical ripening  
1. 
The only pharmacologic cervical ripening agent to be used is vaginal 
misoprostol, 25 mcg every 4 hours with a maximum of six doses.   
2. 
She may or may not have a Foley catheter placed as a method of cervical 
ripening based upon the providing team’s discretion. 
3. 
A Foley catheter will be favored during the cervical ripening phase if there 
is tachysystole and/or a nonreassuring fetal heart tracing precluding further 
misoprostol administration, provided the Bishop score is still <6. 
C. After cervical ripening is achieved, oxytocin and/or artificial rupture of membranes will 
be used at the discretion of the providing team.  
D. If oxytocin is used during the labor induction, the dose will be increased as determined by 
the Family Birth Center Oxytocin low dose infusion regimen.  
E. The remainder of her care during the first, second, and third stages of labor will be at the 
discretion of the providing team.  

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F. All patients’ labor progress will be monitored using a partogram.  Cesarean delivery will 
not be performed for arrest of labor or failed induction unless all criteria have been met as 
outlined by the Family Birth Center Workgroup protocol made effective 6/2/14.  
VI. 
Protocol for the inpatient usual care group (Prospective Study) 
A.  All methods of cervical ripening and labor augmentation will be at the discretion of the 
providing team. Cervical ripening will occur as described above with vaginal misoprostol 
and a Foley catheter; dinoprostone (vaginal prostaglandin, brand name Cervidil) is 
infrequently used in the Family Birth Center but would now be an option as well. 
Oxytocin dosing will be increased by the FBC oxytocin low dose infusion regimen, labor 
will be monitored using a partogram, and Cesarean delivery will continue to be 
determined by the criteria as described above.  
VII. 
Follow-up  
A. Inpatient follow-up  
1. 
We will obtain maternal consent to abstract secondary endpoints as 
described in section 3.3 from the fetal and maternal electronic medical record.  
B. Follow-up over 6 weeks  
1. 
Secondary endpoints from section 3.3 will be abstracted from the EMR. 
2. 
Data collection will stop at 42 days after the patient’s delivery or the date 
of the patient’s final postpartum clinic visit, whichever comes last. 
VIII. Flow chart for Randomized Control Trial 
 

Outpatient vs. inpatient cervical ripening  
 
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IX. 
Flow chart for Prospective Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.2 
Primary Study Endpoints 
The primary endpoint is the mean time from admission to delivery.  
Please note that the time the intervention (outpatient) group spends in the Family Birth 
Center the night before (for fetal heart rate monitoring, Foley placement, etc) will be added into 
the total time of inpatient admission 
3.3 
Secondary Study Endpoints 
I. 
Baseline maternal data  
A. Date of birth 
Continuation of labor 
induction in the inpatient 
setting 
Delivery  
Event monitoring 
(during the inpatient 
postpartum stay) 
Event monitoring 
(6 weeks postpartum) 
Discharge home for 
12 hours 
Control group 
(usual care) 
Intervention group 
(outpatient Foley 
catheter) 
Remain inpatient for 
cervical ripening 
phase 

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B. Race and ethnicity 
C. Pre pregnancy body mass index  
D. Gravidity  
E. Parity 
F. Medical comorbidities 
G. Surgical history  
H. Major complications during this pregnancy (i.e. gestational diabetes)  
II. 
Intervention (outpatient )group data   
A. Method of Foley catheter insertion: digital or sterile speculum  
B. Foley catheter expulsion at home: yes/no, time of expulsion  
C. Return to the Family Birth Center earlier than scheduled and reason (labor, rupture of 
membranes, decreased fetal movement, vaginal bleeding, pain, fever, or other)  
D. Bishop score before Foley placement 
E. Bishop score on the morning of admission for continuation of the labor induction 
F. First induction method used after admission in the morning 
a. Oxytocin  
b. Artificial rupture of membranes 
c. Oxytocin + artificial rupture of membranes 
d. If Foley catheter still in place, Foley + oxytocin  
III. 
Procedural data for both groups  
A. Gestational age at delivery  
B. Primary providing team in the Family Birth Center (Obstetrics, Midwifery, or Family 
Medicine) 
C. Use of Foley catheter: yes/no, date and time   
D. Use of pharmacologic cervical ripening: yes/no, date and time, number of doses  
E. Use of oxytocin: yes/no, date and time, maximum dosage  
F. Rupture of membranes: spontaneous or artificial, date and time  
G. Epidural placement: yes/no, date and time   
H. IV pain medication administration prior to delivery—time, medication, and dose  
I. Date and time of delivery  
J. Number who delivered within 12, 24, 36, 48 hours from initiation of cervical ripening  
K. Number who delivered before midnight of the following day 
L. Meconium passage prior to delivery: yes/no, thin or thick  
M. Total number of cervical exams   
N. Mode of delivery 
1. Normal spontaneous vaginal delivery 
2. Vacuum assisted vaginal delivery and indication  
3. Forceps assisted vaginal delivery and indication   
4. Cesarean delivery   
O. If a cesarean delivery was performed:  
1. Indication for cesarean (non-reassuring fetal heart status, umbilical cord 
prolapse, uterine rupture, placental abruption, failed operative delivery, arrest 
of dilation, arrest of descent, and other) 
2. Type of cesarean—emergent, urgent, or non-urgent (“Alpha,” “Beta,” or 
“Charlie”) 
3. Cervical dilation at the time of cesarean, if known 

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4. Stage of labor at the time of cesarean  
IV. 
Maternal outcomes  
A. Intrapartum complications  
1. 
Intrapartum fever  
2. 
Chorioamnionitis 
3. 
Suspected or confirmed placental abruption  
4. 
Category II or category III fetal heart tracing requiring in utero 
resuscitation as documented in the electronic record during the cervical ripening 
phase only 
B. Estimated blood loss at delivery 
C. Postpartum hemorrhage: yes/no, if pharmacologic or surgical treatments required 
D. Infection (endomyometritis, wound infection, or urinary tract infection within 30 days)  
E. Readmission within 6 weeks of delivery and reason  
F. Length of inpatient hospital stay (in hours from time of admission to noon on the day of 
discharge)  
V. 
Fetal outcomes  
A. Sex 
B. Birth weight (grams)  
C. Position at delivery (occiput anterior, occiput posterior, occiput transverse, or unknown)  
D. APGAR scores at 1 and 5 minutes  
E. Umbilical cord blood gas-pH and base excess  
F. Disposition after delivery: level I, II, or III. If II or III, reason for admission.  
G. Day of life on which discharge occurred  
H. Neonatal death within 30 days and reason  
VI. 
Maternal satisfaction data  
A. Average scores for each question on the maternal satisfaction survey (see attached)  
 
3.4 
Primary Safety Endpoints 
The primary safety outcomes are as follows: heavy vaginal bleeding, severe pain (return to 
hospital overnight for unrelieved pain), mode of delivery, intrapartum complications (as 
described above), and fetal outcomes (as described above). These will include overall fetal and 
maternal survival rates. Based on previous studies, we do not anticipate any difference between 
safety endpoints in the inpatient vs. outpatient groups.  
 
  
4 Subject Selection Enrollment and Withdrawal 
4.1 
Inclusion Criteria 
1. Pregnant women at ≥37 weeks gestation by reliable dating criteria as determined by the 
American College of Obstetricians and Gynecologists (i.e. gestational age supported by 
one of the following: ultrasound prior to 20 weeks of gestation, fetal heart tones 
auscultated by Doppler for 30+ weeks, or documented serum or urine pregnancy test 
36+ weeks ago)  

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2. Scheduled induction of labor with indication and timing supported by the Family Birth 
Center induction of labor guideline entitled “Induction of labor: Indications and 
Timing” 
3. Singleton gestation  
4. Cephalic presentation  
5. Amniotic fluid index greater than or equal to 5 centimeters  
6. Formal prenatal ultrasound documenting the absence of placenta previa 
7. Bishop score <9 and cervical dilation <3cm 
8. The woman is able to give appropriate consent and has undergone an informed consent 
process.  
9. Maternal age ≥ 18 years old at the time of consent.  
4.2 
Exclusion Criteria 
1. New diagnosis requiring immediate hospitalization for monitoring (such as 
preeclampsia) 
2. Vaginal bleeding 
3. Active labor 
4. Premature rupture of membranes as determined by positive ferning and as supported by 
pooling of fluid in the vaginal vault. 
5. Uterine tachysystole (>5 contractions in 10 minutes) 
6. Nonreassuring fetal heart tracing before or after Foley placement 
7. Chorioamnionitis or maternal fever  
8. Intrauterine fetal demise   
9. Contraindication to vaginal delivery, relative or absolute (i.e. transfundal uterine 
surgery) 
10. Abnormal placentation including a low lying placenta 
11. Prior cesarean delivery  
12. Intrauterine growth restriction (growth <10th percentile by formal ultrasound) 
13. Known major fetal anomaly  
14. Human immunodeficiency virus, Hepatitis C, or active herpes infection  
15. Maternal cardiopulmonary disease requiring cardiac monitoring during labor  
16. Pregestational diabetes  
17. Rh isoimmunization  
18. Non-English speaking  
4.3 
Subject Recruitment, Enrollment and Screening 
 
 
We anticipate a targeted population of 400, which includes 200 mothers and their 200 
infants. Data will be collected from these 400 charts after delivery.  
We anticipate that 250 women in total will provide informed consent before giving birth to 
their babies. That is, we estimate that 50 women who are initially consented for the study will 
become ineligible for inclusion in the trial, for example due to spontaneous onset of labor, prior 
to induction of labor. These women will be considered screen failures. 

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4.4 
Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
A patient may be withdrawn from the study for several reasons.  
First, the patient may decide at any time to cease participation in the trial. She will 
receive all appropriate medical cares without consequence of her participation in the trial. If she 
is randomized to the outpatient group, for example, but decides to withdraw before Foley 
placement, her induction of labor will occur in the standard, inpatient fashion. The induction will 
commence either that evening or the next morning, as staffing, unit flow, maternal status, and 
fetal status allow. Similarly, if a woman in the intervention group declines participation in the 
trial after the Foley catheter has been placed, the Foley catheter can be removed with pursuit of 
standard, inpatient cervical ripening. Alternatively, she can keep it in place and elect pain 
management options such as an epidural outside the realm of this study (thereby excluding her 
from the study and committing her to inpatient management).  
Second, the patient may become excluded from the trial for several reasons. A pregnant 
woman may be found to be an eligible participant when she is approached at her clinic visit; 
however, before her scheduled induction of labor that will occur several days later, she may 
become excluded for any of the following reasons:  
1) She develops a new diagnosis (such as preeclampsia) requiring immediate 
hospitalization for monitoring  
2) She develops vaginal bleeding that is unexplained and concerning for labor or 
placental abruption 
3) She spontaneously labors and is admitted for anticipated delivery  
4) She undergoes premature (pre-labor) rupture of membranes 
5) During indicated fetal heart rate monitoring, the tracing becomes non reassuring such 
that outpatient management is not recommended 
6) She develops a fever and/or chorioamnionitis  
7) There is an intrauterine fetal demise  
8) She develops a contraindication to vaginal delivery, such as new active genital 
herpetic lesions  
9) Intrauterine growth restriction is diagnosed  
Finally, the pregnant woman may become excluded from study shortly after arrival to the 
Family Birth Center for initiation of the planned induction of labor. Any of the above-listed 
reasons (vaginal bleeding, spontaneous labor, premature rupture of membranes, etc) diagnosed at 
presentation will be reason to exclude the woman from participation. Furthermore, after Foley 
catheter placement, a patient may be excluded from the trial should any of the following occur:  
1. She is diagnosed with a condition that requires immediate admission for induction of 
labor (such as gestational hypertension or preeclampsia)  
2. She develops vaginal bleeding more than spotting that is clinically concerning for 
placental abruption 
3. She spontaneously labors  
4. She undergoes premature rupture of membranes  
5. The post-placement fetal heart tracing is non reassuring such that outpatient 
management is not recommended  
6. She develops a fever and/or chorioamnionitis  

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4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
Data will not be collected from women who electively withdraw from the study. Data will be 
collected on all women who are randomized to a treatment group. Should patients from the 
outpatient group cross over to the inpatient group (i.e. if they meet exclusion criteria), analysis 
will be by intention to treat.  
 
5 Study Drug  
5.1 
Description 
Please see section 1.2 for a description of the Foley catheter.   
At Mayo clinic, the Foley bulb costs $5.51 for the catheter and all necessary supplies. All 
resident level providers are trained in their first year to insert these catheters at Mayo clinic both 
in simulation models and in the Family Birth Center.  
Please see section 1 for description of previous studies examining the Foley catheter as a 
means of cervical ripening in the outpatient setting. 
5.2 
Treatment Regimen 
Please see sections 1.2 and 1.4.  
5.3 
Method for Assigning Subjects to Treatment Groups in the Randomized Control 
Trial 
Through computer-generated randomization, women will be randomized on the morning of 
planned induction. They will be notified via telephone by the research coordinator. The 
randomization will be stratified by parity (primiparous vs. multiparous) and by body mass index 
(<30 kg/m2 and ≥30 kg/m2).    
5.4 
Preparation and Administration of Study Drug 
The following supplies should be gathered prior to insertion of the Foley catheter: one 16 French 
Foley catheter, one catheter plug, 60 cc of normal saline, one 60 cc syringe, sterile gel, and one 
pair of sterile gloves. The patient is appropriately for a pelvic exam. The examiner dons sterile 
gloves. He or she uses sterile gel and locates the cervical opening digitally. The tip of the Foley 
catheter is guided into cervix and through the internal os. The nurse then places the catheter plug 
in the outflow tract and injects 5 cc of normal saline into the inflow tract. The provider confirms 
that the balloon is in the appropriate position above the internal os. Then, the other 55 cc of 
normal saline are injected. The end of the catheter is taped to the patient’s leg using foam tape.  
Alternatively, depending on provider preference, the catheter can be placed using a 
speculum for guidance. In this case, the patient is placed in the lithotomy position. A speculum is 
inserted after the provider dons sterile gloves. Once the cervix is located, a ring forceps is placed 
on the anterior lip of the cervix. Another ring forceps is placed onto the tip of the catheter and is 
used to guide the catheter into the cervical os. Then, the balloon is inflated with 60 cc normal 
saline as above. Direct visualization confirms appropriate placement of the catheter. All other 
steps as described above are utilized.  
5.5 
Subject Compliance Monitoring 
Not applicable.  

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5.6 
Prior and Concomitant Therapy 
Information about concomitant pharmacologic pain control therapies will be collected. Please see 
the “protocol for the intervention group” in the section 3.1 above for a description of pain control 
options for the outpatient group. As this section states, non pharmacologic options (warm baths, 
massage, frequent position changes, relaxation techniques, gentle stretching), Tylenol, and 
Morphine 10 mg IM  once before discharge are permitted for the intervention group. The 
inpatient group will have the standard array of pain control options that will be left to provider 
discretion.   
5.7 
Packaging 
The Foley catheter will be packaged by the manufacturer. A single device will be in a sterile, 
transparent wrapping.   
5.8 
Masking/Blinding of Study  
There is no blinding in this study. It is not logistically possible to blind either the subjects or their 
providers.    
5.9 
Receiving, Storage, Dispensing and Return 
5.9.1 Storage 
The Foley catheters are already in use commonly on the Family Birth Center, and storage will 
not change. They are not removed from their package until minutes prior to their intended use. 
They may be exposed to light. They are stored in the Family Birth Center supply room, which is 
accessed only by a list of approved personnel using their identification badges.  
5.9.2 Dispensing of Study Drug 
The Foley catheters are already in use commonly on the Family Birth Center, and dispensing will 
not change. The Foley catheters are stored in the Family Birth Center supply room. They will be 
obtained from this supply area individually for placement in each patient. If they are damaged 
inadvertently, they will not be utilized. If they are damaged during placement, the device will be 
discarded and a new catheter will be used.  
 
6 Study Procedures 
6.1 
Clinic visit  
Eligible patients will be identified, educated, and consented as described above in the Study 
Design section (3.1).  
6.2 
Initial arrival to the Family Birth Center (both groups)  
Please see the Study Design section under the headings “Protocol for the intervention 
(outpatient) group” and “Protocol for the inpatient (usual care) comparison/control group.”  
Briefly, all patients will undergo the following upon arrival: 
1. 
Non stress test  
2. 
Ultrasound for fetal presentation  
3. 
Ultrasound for amniotic fluid index  

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(a) 
Not routinely completed in usual care of induction 
of labor. 
4. 
Cervical exam  
5. 
A set of standard questions as described in section 3.1  
6. 
Maternal vital signs 
6.3 
Return to the Family Birth Center after dismissal home (intervention (outpatient) 
group only)  
When a patient in the intervention (outpatient) group is admitted to the hospital, either the next 
morning or any time in the middle of the night, she will undergo the following:  
1. 
Non stress test  
2. 
Ultrasound for fetal presentation  
3. 
Cervical exam  
4. 
Maternal vital signs 
6.4 
Inpatient postpartum stay  
Patients typically remain in the hospital between 24-72 hours after their delivery depending on 
mode of delivery and patient preference. During their inpatient stay, they will have their vitals 
checked per current protocol. Secondary endpoints will be collected during this time frame.  
All subjects will be given the maternal satisfaction survey to complete prior to dismissal 
from the hospital. All efforts will be made by the research team to ensure the patient has 
completed the survey. If she does not complete the survey while in the hospital, she will be 
contacted by phone within the following 2 weeks by a member of the research team to complete 
it over the phone.  
The maternal satisfaction survey has been adapted from the survey utilized by Henry et. al 
[11].  
6.5 
Postpartum follow up  
Secondary endpoints will be collected during the postpartum period. This is defined as 42 days 
after delivery or the final postpartum visit (typically at 6 weeks), whichever occurs later.  
For patients who do not present to their postpartum visit, all available information in the 
electronic medical record will be used to determine the nature of the patient’s postpartum course. 
A significant majority of low-risk obstetric patients live locally; therefore, we do not anticipate 
that adverse events will commonly be diagnosed and treated in other hospital systems.  
 
7 Statistical Plan 
7.1 
Sample Size Determination for Randomized Control Trial 
A power analysis was performed. With 64 patients per arm, we would have 80% power to detect 
a ½ standard deviation reduction in the hospitalization time for the outpatient group vs. the 
inpatient group, assuming a standard deviation of 8 (hours) and a reduction in the mean 
hospitalization time from 16 to 12 (hours) for the inpatient and outpatient groups, 
respectively.  This also assumes a 2-sided significance level of 0.05.   
 
This is a conservative estimate of the effect of the Foley catheter in the outpatient setting 
on pre-delivery hospitalization time, our primary outcome. The trial by Sciscione et al. [10] 

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observed that there was a reduction of 9.6 hours; Henry et al. found a reduction of 11.1 hours 
[11]. If we replicate this finding, we would be able to detect a difference in the primary outcome 
with a smaller number of patients, should we not meet desired enrollment.   
 
7.2 
Sample Size Determination for Prospective Study 
A power analysis was performed and assumed a standard deviation of 8 hours. With 40 subjects 
in the Foley intervention arm and 160 subjects in the standard of care group, we would have 80% 
power to detect a ½ standard deviation reduction in the predelivery hospitalization time from 16 
to 12 hours in the standard of care and intervention groups, respectively. This also assumes a 2-
sided significance level of 0.05. 
7.3 
Statistical Methods 
 
Descriptive Statistics 
Baseline characteristics will be descriptively summarized using mean and standard deviation for 
continuous variables that have a normal Gaussian distributions, and median and interquartile 
range for continuous variables with a skewed distribution. Frequencies and percentages will be 
used to summarize categorical baseline characteristics. Baseline characteristics will be compared 
between the intervention and control groups using the two-sample t-test, Wilcoxon rank sum test, 
and chi square test, as appropriate.   
 
Handling of Missing Data 
Subjects with missing data for the primary outcome will be excluded. Otherwise, missing 
data will be tracked and reported separately. If the amount of missing data within an analysis is 
greater than 10%, imputation methods will be used and the data re-analyzed as a sensitivity 
analysis.   
 
Multiplicity 
We will only evaluate outcomes determined a priori and will report all analyses.  
 
Primary Hypothesis:   
We hypothesize that the mean pre-delivery length of stay will be significantly less in the 
intervention group as compared to the control group. The mean time spent in the hospital 
between the groups will be compared using a 2-sample t-test or the nonparametric equivalent 
(Wilcoxon Rank-Sum test).  
 
Secondary Hypotheses:  
The secondary hypotheses are described below, followed by the statistical tests we plan to 
utilize.  
 
1. Cesarean delivery rates will not differ between the two groups. This hypothesis will be tested 
using the Chi-Square or Fisher’s exact test. Graphical and statistical methods will be used to 
show the data descriptively. We will report frequencies and percentages.  
 

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2. Maternal outcomes (including but not limited to postpartum hemorrhage, infection, hospital 
readmission rates, and satisfaction scores) will not be differ between the two groups. These 
hypotheses will be assessed using the Chi-Square or Fisher’s exact test for categorical endpoints. 
For continuous endpoints, a 2-sample t-test or the nonparametric equivalent (Wilcoxon Rank-
Sum test) will be used. Graphical and statistical methods will be used to show the data 
descriptively. For continuous data, we will also report means, medians, standard deviations, and 
ranges. For categorical data, we will report frequencies and percentages.  
 
3. Fetal outcomes (including but not limited to APGAR scores, umbilical artery pH, and nursery 
disposition) will not differ between the two groups. These hypotheses will be assessed using the 
Chi-Square or Fisher’s exact test for categorical endpoints. For continuous endpoints, a 2-sample 
t-test or the nonparametric equivalent (Wilcoxon Rank-Sum test) will be used. Graphical and 
statistical methods will be used to show the data descriptively. For continuous data, we will also 
report means, medians, standard deviations, and ranges. For categorical data, we will report 
frequencies and percentages. 
 
  
 
7.4 
Subject Population(s) for Analysis 
We will analyze all subjects who were randomized in the randomized control trial design stage 
of the study, except those who electively withdrew from the trial. We will analyze all subjects 
enrolled in the prospective stage of the study, who do not electively withdraw. 
8 Safety and Adverse Events 
8.1 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  
x Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; (6) 
breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
x Unanticipated: (i.e. unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, not listed in the 
Investigator’s Brochure, or not part of an underlying disease. A problem or event is 
"unanticipated" when it was unforeseeable at the time of its occurrence. A problem or 
event is "unanticipated" when it occurs at an increased frequency or at an increased 
severity than expected, AND 
x Related: A problem or event is "related" if it is possibly related to the research procedures. 

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Adverse Event 
An untoward or undesirable experience associated with the use of a medical product (i.e. drug, 
device, biologic) in a patient or research subject. 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  Serious problems/events can be well 
defined and include; 
x death 
x life threatening adverse experience 
x hospitalization 
x inpatient, new, or prolonged; disability/incapacity 
x persistent or significant birth defect/anomaly 
 
and/or per protocol may be problems/events that in the opinion of the sponsor-investigator 
may have adversely affected the rights, safety, or welfare of the subjects or others, or 
substantially compromised the research data. 
 
All adverse events that do not meet any of the criteria for serious, should be regarded as non-
serious adverse events.  
 
Adverse Event Reporting Period 
For this study, the study treatment follow-up period is defined as 42 days following delivery, or 
the date of the final postpartum visit (typically at 6 weeks), whichever comes last.  
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
should be recorded as an adverse event if the frequency, intensity, or the character of the 
condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an adverse event must also be recorded and documented as an adverse 
event.  
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the sponsor-investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the sponsor-investigator should instruct each subject to report, to the sponsor-
investigator, any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.  
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise in 

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this protocol.  Any condition responsible for surgery should be documented as an adverse event 
if the condition meets the criteria for an adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an 
adverse event in the following circumstances:  
-Hospitalization or prolonged hospitalization for diagnostic procedures and/or therapy for 
a preexisting condition. Surgery should not be reported as an outcome of an adverse event if the 
purpose of the surgery was elective or diagnostic and the outcome was eventful.  
 
-Hospitalization or prolonged hospitalization for diagnostic procedures, therapy, and/or 
surgery for all intrapartum and postpartum events, unless it is a worsening or increase in 
frequency of hospital admissions as judged by the clinical investigator.    
8.2 
Recording of Adverse Events 
At each contact with the subject, the study team must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event section of the case report form (CRF). All clearly related signs, symptoms, and abnormal 
diagnostic, laboratory or procedure results should recorded in the source document. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious adverse event that occurs after the study period and is considered to 
be at least possibly related to the study treatment or study participation should be recorded and 
reported immediately. 
8.3 
Reporting of Serious Adverse Events and Unanticipated Problems 
When an adverse event has been identified, the study team will take appropriated action 
necessary to protect the study participant and then complete the Study Adverse Event Worksheet 
and log.  The sponsor-investigator will evaluate the event and determine the necessary follow-up 
and reporting required. 
 
8.3.1 Sponsor-Investigator reporting: notifying the Mayo IRB 
The sponsor-investigator will report to the Mayo IRB any UPIRTSOs and Non-UPIRTSOs 
according to the Mayo IRB Policy and Procedures. 
  
Information collected on the adverse event worksheet:  
x Subject’s name:  
x Medical record number:  
x Disease/histology (if applicable):  
x The date the adverse event occurred:  
x Description of the adverse event:  
x Relationship of the adverse event to the research (drug, procedure, or intervention):  
x If the adverse event was expected:  

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x The severity of the adverse event:  
x If any intervention was necessary:  
x Resolution: (was the incident resolved spontaneously, or after discontinuing treatment) 
x Date of Resolution:  
 
The sponsor-investigator will review all adverse event reports to determine if specific reports 
need to be made to the IRB and FDA.  The sponsor-investigator will sign and date the adverse 
event report when it is reviewed.  For this protocol, only directly related SAEs/UPIRTSOs will 
be reported to the IRB. 
 
8.4 
Unmasking/Unblinding Procedures 
This study is not blinded.  
8.5 
Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan (see section 10  “Study Monitoring, Auditing, and Inspecting”).  Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
  
9 Data Handling and Record Keeping 
9.1 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
x What protected health information (PHI) will be collected from subjects in this study 
x Who will have access to that information and why 
x Who will use or disclose that information 
x The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (long term survival status that 
the subject is alive) at the end of their scheduled study period. 
9.2 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.  Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 

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records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
9.3 
Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study.  All 
data requested on the CRF must be recorded.  All missing data must be explained.  If a space on 
the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”.  If the item is not applicable to the individual case, write “N/A”.  All entries should be 
printed legibly in black ink.  If any entry error has been made, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it.  All such 
changes must be initialed and dated.  Do not erase or use “white-out” for errors.  For clarification 
of illegible or uncertain entries, print the clarification above the item, then initial and date it.  If 
the reason for the correction is not clear or needs additional explanation, neatly include the 
details to justify the correction.  
 
Data Management 
All data will be manually abstracted from the electronic medical record and recorded in the 
RedCap database by the Co-Principal Investigator.  
 
Data Security and Confidentiality 
Only necessary research team members will have access to the data for data entry or analysis. All 
data collection and analysis will be performed behind the Mayo firewall.  
 
Data Quality Assurance 
One trained team member, , will perform all data entry. A second team member will 
independently collect data on every 50th patient, and a comparison of data points between the 
first and second team members will be performed for quality assurance. 
 
Data Clarification Process 
Incomplete and outlying data points will be corrected as needed by reviewing the patient’s 
electronic medical record.  
9.4 
Records Retention 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents   
 
Subject-specific data and Case Report Forms will be identified by the patient’s medical record 
number and a unique number given in order of patient randomization; the patient’s name will not 
be included. The subject identification list will be stored behind the Mayo firewall.  
 
Subject names and other directly identifiable information will not on any reports, publication, sor 
other disclosures of clinical study outcomes.  
 
The sponsor-investigator will retain the specified records and reports: 
1. As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy”  

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10 Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
The investigator will allocate adequate time for such monitoring activities.  The Investigator will 
also ensure that the monitor or other compliance or quality assurance reviewer is given access to 
all the study-related documents and study related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.), and has adequate space to conduct the monitoring visit. 
 
As a service to the sponsor-investigator, this study may be monitored during the conduct of the 
trial by staff from the Mayo Clinic Office of Research Regulatory Support.  Clinical trial 
monitoring may include review of the study documents and data generated throughout the 
duration of the study to help ensure the validity and integrity of the data along with the 
protection of human research subjects.  This will assist sponsor-investigators in complying with 
Food and Drug Administration regulations. 
 
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, and government regulatory agencies, of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 
11 Ethical Considerations 
This study is to be conducted according to United States government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the Approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject or the subject’s legally authorized representative, and the individual obtaining the 
informed consent. 
 

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This study involves a vulnerable population, namely pregnant women. All criteria as specified in 
“Special categories of research: Pregnant women, human fetuses, and neonates” delineated by 
the Mayo Clinic Office for Human Research Protection have been met to perform research 
involving pregnant women. 
 
12 Study Finances 
12.1 Funding Source 
This study is financed through grants from both the Obstetrics and Gynecology Research 
Committee and the Obstetrics and Gynecology Education Committee.   
 
12.2 Conflict of Interest 
None of the authors or study team members have a conflict of interest with this study including 
financial gain.  
13 Publication Plan 
There are no specific publication requirements from the funding agencies for this study. Dr. 
Vanessa Torbenson, replacing Dr. Mary Catherine Tolcher upon her departure from Mayo Clinic 
in June of 2016, holds primary responsibility for publication of the results this study. Her 
approval is required before any information can be published, used, or passed on to a third party.  
This study will be registered to ClinicalTrials.gov prior to subject enrollment in the trial. 
The primary results will be posted to ClinicalTrials.gov within 12 months of final data collection.  
 
14 References 
1.  Martin, J., Hamilton, BE, Sutton, PD, et al. Births: final data for 2012. National Vital 
Statistic Reports 2014. p. 1-68.  
2. American College of Obstetricians and Gynecologists. Patient safety and quality 
improvement: reVITALize obstetric data definitions. http://www.acog.org/About-
ACOG/ACOG-Departments/Patient-Safety-and-Quality-Improvement/reVITALize-
Obstetric-Data-Definitions. Accessed April 19th, 2015.  
3. Bishop, E.H. Pelvic scoring for elective induction. Obstetrics and gynecology, 1964. 24: 
p. 266-8.  
4. Mozurkewich, E.L., et al. Methods of induction of labour: a systematic review. BMC 
pregnancy and childbirth, 2011. 11: p.84.  
5. Kelly, A.J., Z. Alfirevic, and A. Ghosh. Outpatient versus inpatient induction of labour 
for improving birth outcomes. The Cochrane database of systematic reviews, 2013. 11: 
p. CD007372.  
6. Wilkinson, C., et al. A randomised controlled trial of outpatient compared with inpatient 
cervical ripening with prostaglandin E2 (OPRA study). BJOG: an international journal 
of obstetrics and gynaecology, 2015. 122 (1): p.94-104.   
7. Jozwiak, M., et al. Mechanical methods for induction of labour. The Cochrane database 
of systematic reviews, 2012. 3: p. CD001233. 

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8. Sciscione, A.C. Methods of cervical ripening and labor induction: mechanical. Clinical 
obstetrics and gynecology, 2014. 57(2): p. 369-76. 
9. Sciscione, A.C., et al.. The timing of adverse events with Foley catheter preinduction 
cervical ripening; implications for outpatient use. American journal of perinatology, 
2014. 31(9): p. 781-6.  
10. Sciscione, A.C., et al. Transcervical Foley catheter for preinduction cervical ripening in 
an outpatient versus inpatient setting. Obstetrics and gynecology, 2001. 98(5): p. 751-6. 
11. Henry, A., et al. Outpatient Foley catheter veresus inpatient prostaglandin E2 gel for 
induction of labour: a randomised trial. BMC pregnancy and childbirth, 2013. 13 (25): 
p.13-25. 
12. Howard, K., et al., Women's preferences for inpatient and outpatient priming for labour 
induction: a discrete choice experiment. BMC health services research, 2014. 14: p. 330.  
13. Delaney, S., et al. Labor induction with a Foley balloon inflated to 30 mL compared 
with 60 mL: a randomized controlled trial. Obstetrics and gynecology, 2010. 115 (6): p. 
1239-45.  
14. Pennell, C.E., et al. Induction of labour in nulliparous women with an unfavourable 
cervix: a randomised controlled trial comparing double and single balloon catheters 
and PGE2 gel. British journal of obstetrics and gynecology, 2009. 116 (11): p.1443-52.