Clinical trial NCT02487797
Conditions: Dystocia
Sponsor: Northwestern University
Start date: 2015-09-28; Completion date: 2020-09-28
Enrollment: 1003 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Oxytocin is a medication that is often used to strengthen contractions to overcome delayed labor progress. The primary aim of this study is to determine whether receiving a higher dose of oxytocin lowers the chance of needing a cesarean section when compared to a lower dose of oxytocin. Other aims include examining the relationship between dose of oxytocin regimen and length of labor, postpartum hemorrhage, intrauterine infection, umbilical cord gas, neonatal Apgar score \<5 at 5 minutes, and need for neonatal intensive care.

Detailed description:
This randomized double blind clinical trial of consenting nulliparous women in spontaneous labor who require oxytocin for labor augmentation seeks to determine whether use of a high dose oxytocin regimen improves obstetric outcomes when compared with a low dose oxytocin regimen, in a manner that is safe for both mother and neonate.

This project will include 1002 women recruited from the obstetrical service at Prentice Women's Hospital. Women will be included if they are at least 36 weeks gestation, have a singleton pregnancy, and have been diagnosed with spontaneous labor or spontaneous rupture of membranes. Women will be exposed to oxytocin for the indication of labor augmentation at the discretion of their obstetric provider.

Women will be randomized with equal probability to intervention group using a fixed allocation procedure. To maintain a double blind design, the Prentice Women's Hospital pharmacy will carry out the randomization of oxytocin solutions according to the random assignment so that neither the women or their care providers nor the investigators will know the identity of the intervention assignment. The low-dose oxytocin regimen group will receive a starting oxytocin regimen concentration rate of 2 milliunits/minute that can be increased at increments of 2 milliunits/minute, as per the discretion of their obstetric provider. The high-dose oxytocin regimen group will receive a starting oxytocin regimen concentration rate of 6 milliunits/minute that can be increased at increments of 6 milliunits/minute, as per the discretion of their obstetric provider.

Once the women are enrolled, randomized, and in receipt of their assigned interventions, further clinical management will be left to the discretion of each woman's obstetric provider.

Prior to discharge from the hospital, baseline demographic and clinical data will be obtained via chart review.

Arms: arm 1: The oxytocin solution will be prepared using 90 units of oxytocin in 500 milliliters of normal saline (sodium chloride 0.9%). The oxytocin infusion will be initiated with a starting oxytocin concentration rate of 6 milliunits/minute (volume rate 2 milliliters/hour) that can be increased at increments of 6 milliunits/minute (volume rate 2 milliliters/hour) every 15-30 minutes until a labor pattern with uterine contractions every 2-3 minutes of moderate to strong intensity is established. arm 2: The oxytocin solution will be prepared using 30 units of oxytocin in 500 milliliters of normal saline (sodium chloride 0.9%). The oxytocin infusion will be initiated with a starting oxytocin concentration rate of 2 milliunits/minute (volume rate 2 milliliters/hour) that can be increased at increments of 2 milliunits/minute (volume rate 2 milliliters/hour) every 15-30 minutes until a labor pattern with uterine contractions every 2-3 minutes of moderate to strong intensity is established.
Interventions: intervention 1: Oxytocin intervention 2: Sodium Chloride 0.9%
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 1 of 23
Revised Template: November 10, 2014
PROTOCOL TITLE:
A randomized double blind clinical trial comparing oxytocin low-dose and high-dose 
regimens for labor augmentation
INVESTIGATORS:
Principal Investigator
Alan M. Peaceman, MD
Professor
Chief of the Division of Maternal Fetal Medicine
Department of Obstetrics and Gynecology
Northwestern University Feinberg School of Medicine
Chief of Obstetrics
Northwestern Memorial Hospital - Prentice Women’s Hospital
Amp066@northwestern.edu
312-472-4657 (office)
250 E. Superior Street, Suite 05-2149
Chicago IL 60611
Co-Investigator
Moeun Son, MD, MSCI
Adjunct Assistant Professor
Department of Obstetrics and Gynecology
Northwestern University Feinberg School of Medicine
Moeun.son@northwestern.edu
Co-Investigator
Bethany T. Stetson, MD
Assistant Professor
Division of Maternal-Fetal Medicine
Department of Obstetrics and Gynecology
Northwestern University Feinberg School of Medicine
Bethany.schmidt@northwestern.edu
VERSION NUMBER: 
Version 7
VERSION DATE:
July 16, 2019
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 2 of 23
Revised Template: November 10, 2014
Table of Contents
1.0
Objectives ....................................................................................................3
2.0
Background..................................................................................................3
3.0
Inclusion and Exclusion Criteria...................................................................4
4.0
Study-Wide Number of Subjects..................................................................6
5.0
Study-Wide Recruitment Methods ...............................................................6
6.0
Multi-Site Research......................................................................................6
7.0
Study Timelines ...........................................................................................6
8.0
Study Endpoints...........................................................................................6
9.0
Procedures Involved ....................................................................................7
10.0
Data and Specimen Banking .....................................................................10
11.0
Data and Specimen Management .............................................................10
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects ..............13
13.0
Withdrawal of Subjects*.............................................................................14
14.0
Risks to Subjects*......................................................................................15
15.0
Potential Benefits to Subjects ....................................................................16
16.0
Vulnerable Populations..............................................................................16
17.0
Community-Based Participatory Research................................................16
18.0
Sharing of Results with Subjects ...............................................................16
19.0
Setting........................................................................................................16
20.0
Resources Available ..................................................................................17
21.0
Prior Approvals ..........................................................................................18
22.0
Recruitment Methods.................................................................................19
23.0
Local Number of Subjects..........................................................................19
24.0
Confidentiality ............................................................................................19
25.0
Provisions to Protect the Privacy Interests of Subjects..............................19
26.0
Compensation for Research-Related Injury...............................................20
27.0
Economic Burden to Subjects....................................................................20
28.0
Consent Process........................................................................................20
29.0
Process to Document Consent in Writing ..................................................21
30.0
Drugs or Devices .......................................................................................21
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 3 of 23
Revised Template: November 10, 2014
1.0
Objectives
1.1
Objectives: 
i.
Determine the rate of cesarean delivery in women who receive 
high-dose oxytocin regimen (HDOR) compared to women who 
receive low-dose oxytocin regimen (LDOR) for augmentation of 
labor.
ii.
Determine the rates of several measures of maternal morbidity in 
women who receive HDOR compared to women who receive 
LDOR. The measures of maternal morbidity that will be examined 
are labor duration (time interval from admission to labor and 
delivery to delivery of neonate), postpartum hemorrhage, and 
intrauterine infection.
iii.
Determine the rates of several measures of morbidity in neonates 
born to women who receive HDOR compared to women who 
receive LDOR.  The measures will be examined as a composite 
outcome and will include perinatal death, umbilical cord arterial 
pH less than 7.0 or base excess greater than 12, Apgar scores at 
five minutes of less than <=3, admission to neonatal intensive 
care unit (NICU) for greater than 48 hours, severe respiratory 
distress requiring cardiorespiratory support and/or ventilation 
(intubation, continuous positive airway pressure, high-flow nasal 
cannula) for more than 12 hours, major birth injury (brachial 
plexus injury, bone fractures, other neurologic injury, facial nerve 
injury), neonatal encephalopathy, neonatal seizure, need for 
hypothermic treatment (cooling), and neonatal sepsis (positive 
blood, urine, or cerebrospinal fluid culture; or in the absence of 
positive culture(s), clinical evidence of cardiovascular collapse or 
an unequivocal X-ray confirming infection).
1.2
Hypothesis: The use of HDOR for labor augmentation will lower the 
incidence of dysfunctional labor and the subsequent need for cesarean 
delivery compared to the use of LDOR. We hypothesize that women who 
receive HDOR will have shorter labor durations, as well as lower rates of 
postpartum hemorrhage and intrauterine infection. Furthermore, we 
hypothesize that there will be no significant difference in morbidity in 
neonates born to women who receive HDOR compared to women who 
receive LDOR.  
2.0
Background
One in three pregnant women undergo cesarean delivery in the United States.1 
Cesarean deliveries have increased at an alarming rate without a concomitant 
improvement in maternal and neonatal outcomes.  Rather, the increasing rate has 
become a major health concern, as cesarean deliveries are associated with significant 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 4 of 23
Revised Template: November 10, 2014
maternal morbidity, increased costs, and adverse implications for future pregnancies.2-4 
The factor that has contributed the most to the increase in cesarean deliveries is the 
increased frequency of labor dystocia (i.e. dysfunctional labor due to ineffective uterine 
contractions).5,6 In an effort to avoid the need for a cesarean delivery when labor fails to 
progress, oxytocin is widely used to augment contractions.  In fact, in 2003, 645,075 
pregnant women (17% of all women in the United States who gave birth and were 
registered) received oxytocin augmentation.  Though this statistic has no longer been 
reported in the CDC National Vital Statistics Reports since 2003, this percentage has 
likely further increased. While the total dose amount of oxytocin needed to produce a 
clinical response (i.e. progressive cervical dilation) may vary from patient to patient, the 
optimal dosing rate needed to achieve this endpoint has not yet been established. 
Oxytocin dose protocols have been categorized into ‘high’ versus ‘low’ dose regimens, 
but these terms are to an extent, misnomers because the difference is typically in the 
rate of dose increase rather than the total dose used. Both protocols titrate the dose of 
oxytocin to achieve a frequency of uterine contractions (usually 4 to 5 contractions in a 
10-minute interval) that is usually sufficient to result in progressive labor, and thus the 
target total dose should theoretically be similar. Numerous oxytocin dose protocols that 
vary in initial dose, incremental dose increase, and the time interval between dose 
increases have been studied. HDOR have been associated with significantly shorter 
labor duration and lower cesarean delivery rates, when compared to LDOR,7-13 without 
adverse effects on the newborn.  It is postulated that by more rapidly progressing to the 
required therapeutic dose, cervical dilation is achieved more quickly, and the likelihood 
of a spontaneous vaginal delivery is increased. Furthermore, use of HDOR showed 
trends toward lower rates of postpartum hemorrhage and intrauterine infection for the 
mother. 
Despite these positive findings, use of LDOR has become the prevailing obstetric 
practice in the United States.14 The preference for LDOR stems from unsubstantiated 
concerns that HDOR are associated with more uterine tachysystole (defined as more 
than 5 contractions in 10 minutes, averaged over a 30-minute window), which could 
lead to higher rates of neonatal morbidity.15-17 Prior studies have refuted this conclusion 
by showing similar neonatal outcomes when comparing use of HDOR and LDOR. 
However, the adoption of HDOR has been very uncommon due to persisting safety 
concerns and criticisms that prior studies had small sample sizes, inappropriate 
eligibility criteria, and inherent biases in study design.  
As the frequency of cesarean deliveries performed for labor dystocia continues to 
increase, it is timely and critical to address the controversy surrounding the oxytocin 
dose regimens with an adequately powered prospective randomized trial.  It is 
imperative that the study is double blinded to both care providers and patients to 
eliminate the subjective and unintentional biases that are likely contributing to the slow 
adoption of high-dose regimens that are effectively used for labor augmentation in other 
parts of the world.18 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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The overarching goal of the proposed study is to conduct a double blind 
randomized trial to determine whether the use of HDOR is effective in lowering 
the incidence of cesarean delivery in a manner that is safe for both mother and 
neonate. Our data will allow us to help establish evidence-based guidelines for the 
optimal use of oxytocin for labor augmentation.  Furthermore, this project will allow us to 
build a foundation for a program of research to study other approaches to the 
management of labor dystocia.  Our long-term goal is to conduct research that will 
develop a better knowledge base to guide clinical decisions and encourage policy 
changes that can lead to safe prevention of cesarean delivery, both at Northwestern 
Memorial Hospital (NMH) and nationally. 
3.0
Inclusion and Exclusion Criteria
3.1
Nulliparous women with singleton gestations who require oxytocin for labor 
augmentation will be recruited for the proposed study.  Pregnant women 
who present to the Northwestern Memorial Hospital Prentice Women’s 
Hospital (NMH-PWH) Obstetric Triage Unit for obstetric evaluation will be 
screened for eligibility.  Subjects meeting eligibility criteria will be 
approached for potential recruitment, with the assent of their primary 
obstetric physicians and midwives, once their hospital admission for a trial 
of labor has been confirmed.
3.2
Criteria
i.
Inclusion criteria: 
o
Able to give informed written consent
o
Age ≥18 years
o
Nulliparous
o
Pregnant with a singleton gestation that is equal to or greater 
than 36 weeks.
o
Diagnosed with at least 6 regular uterine contractions within 
60 minutes of observation. In addition, at least one of the 
following: cervix greater than or equal to 3 cm dilated or 80% 
effaced OR spontaneous rupture of membranes
o
Subject’s attending obstetric physician or midwife has 
determined that the subject needs administration of oxytocin 
infusion for labor augmentation.  Labor augmentation will be 
defined as stimulation of uterine contractions when 
spontaneous contractions have failed to result in progressive 
cervical dilation or descent of fetus.
ii.
Exclusion criteria:
o
History of prior cesarean section or uterine surgery 
o
Fetus in non-cephalic presentation 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 6 of 23
Revised Template: November 10, 2014
o
Subject undergoing labor induction (i.e. receipt of 
cervical ripening with intracervical foley balloon 
placement or prostaglandins)
o
Non-English speaking
3.3
Special Populations 
i.
Adults unable to consent: Subjects who are unable to consent will not 
be included in our study.
ii.
Individuals who are not yet adults (infants, children, teenagers): Our 
study will only include subjects who are adults, and are 18 -45 years of 
age.
iii.
Pregnant women: This population will be included since our study is 
focused specifically on the obstetric population. 
iv.
Prisoners: This is not applicable to our study; we will recruit solely from 
the population of pregnant women who deliver at Northwestern 
Memorial Hospital – Prentice Women’s Hospital.
4.0
Study-Wide Number of Subjects – Not applicable
5.0
Study-Wide Recruitment Methods – Not applicable as this is a single-center 
clinical trial
6.0
Multi-Site Research - Not applicable as this is a single-center clinical trial
7.0
Study Timelines
7.1
Timelines
i.
After informed consent is obtained, subjects will be enrolled in the 
study if and when their primary obstetric physician or midwife 
determines that oxytocin needs to be initiated for labor augmentation. 
The individual subject will be expected to participate in the study from 
the time of enrollment until time of discharge from the hospital after 
delivery.
ii.
Previous work by the principal investigator (A.M.P.) showed that Active 
Management of Labor, with HDOR as one of its components, reduced 
the rate of labor dystocia and thus the rate of cesarean delivery, 
without increasing maternal or neonatal morbidity.10 This randomized 
trial was conducted at NMH and recruited 720 patients (75% of eligible 
women participated in the study) in a 12-month period.  Recent 
hospital data revealed that 3,466 women in the 12-month period prior 
to the original study proposal would have meet eligibility criteria. As of 
July 22, 2019, 839women have been enrolled in this study.
iii.
The estimated date for completion of this study including primary 
analyses of the data is 4 years after the start of the clinical trial.  
Patient recruitment commenced in September 2015, and we expect to 
complete primary analyses by November 2019. 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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8.0
Study Endpoints
8.1
Study Endpoints
i.
Primary study endpoint:
o
The incidence of cesarean delivery
ii.
Secondary study endpoints:
o
Measures of maternal morbidity
a. Length of labor duration (defined as the 
number of hours from admission to labor and 
delivery to delivery of neonate)
b. Incidence of postpartum hemorrhage (defined 
as an estimated blood loss greater than 500 
mL for vaginal delivery or greater than 1000 
mL for cesarean delivery)
c. Incidence of intrapartum chorioamnionitis 
(defined as fever great than 100.4° Fahrenheit 
in the intrapartum period with the initiation of a 
therapeutic antibiotic regimen in the 
intrapartum period)
d. Incidence of postpartum endometritis (defined 
as fever greater than 100.4° Fahrenheit in the 
postpartum period with the initiation of a 
therapeutic antibiotic regimen in the 
postpartum period)
8.2
Safety Endpoints
i.
Primary safety endpoint:
o
Cesarean delivery performed for primary indication of non-
reassuring fetal status
ii.
Secondary safety endpoints:
o
Measures of neonatal morbidity
a. Stillbirth or neonatal death
b. Umbilical cord arterial blood pH less than 7.0 
or base deficit greater than 12 mmol/L; or cord 
venous blood pH less than 7.0 or base deficit 
greater than 12 mmol/L when umbilical artery 
values are not available. 
c. Neonatal Apgar score at five minutes of life of 
less than 3
d. Admission to Neonatal Intensive Care Unit (NICU)
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 8 of 23
Revised Template: November 10, 2014
i. Length of stay in NICU, if applicable
e. Additional morbidities: severe respiratory distress 
requiring cardiorespiratory support and/or ventilation 
(intubation, continuous positive airway pressure, high-
flow nasal cannula) for more than 12 hours, major 
birth injury (brachial plexus injury, bone fractures, 
other neurologic injury, facial nerve injury), neonatal 
encephalopathy, neonatal seizure, need for 
hypothermic treatment (cooling), and neonatal sepsis 
(positive blood, urine, or cerebrospinal fluid culture; or 
in the absence of positive culture(s), clinical evidence 
of cardiovascular collapse or an unequivocal X-ray 
confirming infection).
9.0
Procedures Involved
9.1
Study Design: We propose a double blind randomized clinical trial:
i.
Recruitment: Patients meeting eligibility criteria (as listed above) 
will be approached for potential recruitment, with the assent of 
their primary obstetric physician or midwife, once their hospital 
admission for a trial of labor has been confirmed.
ii.
Intervention: After informed consent is obtained, subjects will be 
enrolled if and when their primary obstetric physician or midwife 
determines that oxytocin is to be initiated for labor augmentation. 
One group, labeled as LDOR, will undergo our primary 
institutional protocol (Protocol #12.0053) with a starting oxytocin 
concentration rate of 2mU/min that can be increased at 
increments of 2mU/min, as per the discretion of each individual’s 
primary obstetric physician or midwife. The other group, labeled 
as HDOR, will undergo our supplemental institutional protocol for 
Active Management of Labor (Protocol #12.005m Appendix A) 
with a starting oxytocin concentration rate of 6mU/min that can be 
increased at increments of 6mU/min, as per the discretion of each 
individual’s primary obstetric physician or midwife. The solutions 
used in the two groups will appear identical and volume infusion 
rates (2mL/hour) will be identical to ensure double blinding.  The 
sole difference between the two groups will be the oxytocin 
concentration, with 30U oxytocin in 500mL of 0.9% normal saline 
(NS) in the LDOR group and 90U oxytocin in 500mL of 0.9% NS 
in the HDOR group.  Once a patient is enrolled, randomized, and 
in receipt of the assigned intervention, further clinical 
management will be left to the discretion of each patient’s primary 
obstetric physician or midwife.  Each subject will have a unique 
drug code, which will remain with her for the trial duration, and 
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PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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drug preparations will be labeled with the same unique code by 
the pharmacy. 
iii.
Randomization: Fixed allocation procedure will assign the 
interventions to subjects with equal probability using a blocked 
randomization scheme without stratification.  To maintain a 
double blind design, the NMH Investigational Pharmacy will carry 
out the randomization and preparation of oxytocin solutions 
according to the random assignment so that neither the patients 
and their care providers nor the investigators will know the identity 
of the intervention assignment. 
9.2
Emergency unblinding procedures will be established so that patient safety 
is not jeopardized.  Once a patient is enrolled, randomized, and in receipt of 
the assigned intervention, further clinical management will be left to the 
discretion of each subject’s primary obstetric physician or midwife.  
9.3
Procedures to lessen the probability or magnitude of risks:
i.
Continuous external fetal monitoring (EFM) will be required during 
oxytocin infusion for both treatment groups. As per established 
institutional clinical protocol (Protocol #12.0053), each subject will be 
monitored closely during oxytocin infusion. Specifically, in latent labor, 
the subject’s clinical nurse will assess and document contraction 
intensity, duration and frequency as well as fetal heart rate (FHR) 
baseline, variability, and any periodic change every 30 minutes and 
with each oxytocin rate change.  In active labor and stage 2 of labor, 
the subject’s clinical nurse will assess and document contraction 
intensity, duration and frequency as well as FHR baseline, variability, 
and any periodic change every 15 minutes and with each oxytocin rate 
change.  If a tachysystole contraction pattern (defined as more than 5 
contractions in 10 minutes, averaged over a 30-minute window) is 
identified, the oxytocin infusion will be decreased to the previous 
milliunit rate setting and reevaluated in 15 minutes. If a tachysystole 
pattern persists at this first 15 minute-mark, the oxytocin infusion will 
be decreased by one-half the current rate, and reevaluated again in 15 
minutes.  If a tachysystole pattern persists at this second 15-minute 
mark, the oxytocin infusion will be discontinued. The oxytocin infusion 
may then be restarted if the FHR is normal, and contraction frequency, 
intensity, and duration are normal at the initial start dose.  If a FHR 
pattern is deemed to be Category 2, the subject’s primary obstetric 
physician or midwife will be required to visualize the EFM recording 
and will determine further oxytocin titration.  For a prolonged 
deceleration (defined as a decrease in FHR from baseline lasting more 
than two minutes), the oxytocin infusion will be discontinued.  If a FHR 
pattern is deemed to be Category 3 (absent baseline FHR variability 
with any of the following: recurrent late decelerations, recurrent 
variable decelerations, bradycardia, or sinusoidal pattern), the oxytocin 
infusion will be discontinued, and the primary obstetric physician or 
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PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
Page 10 of 23
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midwife will be notified.  If the oxytocin has been discontinued for a 
Category 2 or 3 pattern, the oxytocin may be restarted per the order of 
the primary obstetric physician or midwife when the FHR tracing has 
returned to a Category 1 or reassuring Category 2 tracing at no more 
than one-half the dose that preceded the discontinuation.  Maternal 
pulse, respirations, and blood pressure will be evaluated and recorded 
hourly or more frequently if necessary based on patient status.  
Maternal temperature will be evaluated every 2 hours with intact 
membranes, and every hour following rupture of membranes.  
ii.
Subjects in the LDOR group will receive standard oxytocin infusion 
according to the established NMH Clinical Protocol for Induction and 
Augmentation of Labor, Protocol #12.0053 (protocol is attached).  In 
accordance with this protocol, the oxytocin infusion will be started at a 
rate of 2 mU/min (to maintain blinded design, pump rate will be “set” at 
2 mL/hr with a concentration of 30 U oxytocin in 500mL of 0.9% NS) 
for the subjects in the LDOR group. The rate will be increased by 2 
mU/min no more frequently than every 15-30 minutes until a labor 
pattern with uterine contractions every 2-3 minutes of moderate to 
strong intensity is established.  Subjects in the HDOR group will 
receive oxytocin infusion according to the established supplemental 
NMH Clinical Protocol for Induction and Augmentation of Labor, 
Protocol #12.0053 (Appendix A – Active Management of Labor).  In 
accordance with this supplemental protocol, the oxytocin infusion will 
be started at 6 mU/min (to maintain blinded design, pump rate will be 
“set” at 2 mL/hr with oxytocin concentration of 90 U oxytocin in 500mL 
of 0.9% NS) for the subjects in the HDOR group. The rate will be 
increased by 6mU/min (to maintain blinded design, pump rate will be 
“increased” by 2 mL/hr with oxytocin concentration of 90 U oxytocin in 
500mL of 0.9% NS) until a labor pattern with uterine contractions every 
2-3 minutes of moderate to strong intensity is established. 
iii.
The medical record of each subject’s hospital stay will be reviewed and 
used to collect data. A data collection form will be utilized by the study 
investigators to extract data from each subject’s medical record (‘data 
collection’ form attached) 
9.4
Clinical data that are pertinent to the study endpoints during the hospital 
stay will be collected (see ‘data collection form’).  There will be no long-term 
follow-up; the study period begins at randomization and ends with discharge 
from hospital following delivery.  Data will be collected only up until time of 
each subject’s hospital discharge.
9.5
Not applicable
10.0
Data and Specimen Banking
10.1 The principal investigator Dr. Alan Peaceman,co-investigators Dr. Moeun 
Son and Dr. Bethany Stetson, and research assistant Dr. Archana Roy will 
serve as custodians of all research data. As stewards of the research data, 
these individuals will be responsible and accountable for research data as it 
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PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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is collected, processed, stored, analyzed, and reported.  Every effort will be 
made to maintain high quality data that will remain protected and kept 
strictly confidential in accordance with local, state, and federal law; as such, 
institutional resources REDCap (Research Electronic Data Capture) and 
NITRO Study Tracker will be used for data entry and monitoring. Once all 
data collection forms and medical charts have been reviewed, all identifiers 
will be removed and subject data will be stored and archived in a de-
identified manner.  The identifiable data will be permanently discarded by 
permanently deleting the password protected encrypted database with 
patient identifiers at the earliest opportunity.
10.2 Once the data collection forms and medical charts have been reviewed, all 
identifiers will be removed, and patient data will be stored in a de-identified 
manner (for the list of data to be stored, please see attached ‘stored data’ 
form).  Data will be stored in accordance with Northwestern University 
Information Technology (NUIT) File Sharing Policy using SharePoint and 
Northwestern file servers, which are available for storing and sharing 
sensitive research data in order to maintain confidentiality and privacy. Only 
the study investigators who are on the Authorized Personnel list of the IRB 
approved protocol will be granted access to the research data.
10.3 De-identified data will be stored in accordance with NUIT File Sharing Policy 
using SharePoint and Northwestern file servers, which are available for 
storing and sharing sensitive research data in order to maintain 
confidentiality and privacy. Only the study investigators who are on the 
Authorized Personnel list of the IRB approved protocol will be granted 
access to the research data. 
11.0
Data and Specimen Management
11.1 Data Analysis Plan: All outcome data will be collected and entered into the 
computer database before breaking the code and revealing intervention 
assignment. All analyses will be performed using the intention to treat 
principle. Descriptive statistics (means, standard deviations, proportions) will 
be calculated to check for any major differences in the study groups with 
regard to patient demographics and other baseline characteristics. All 
univariate comparisons will be unpaired and all tests of significance will be 
two tailed. For univariate analysis, continuous variables will be compared by 
Student’s t-test. Categorical data will be compared using Chi-square testing 
or Fisher’s Exact Test, depending on sample size.  All values will be 
expressed as the mean + standard error (continuous variables) or as a 
percentage of the group from which they were derived (categorical 
variables). A p value of less than 0.05 will be considered statistically 
significant. An interim analysis of the first 100 patients will be performed by 
an independent expert physician, and the Haybittle-Peto rule will be used as 
a guide for stopping the trial if the analysis of the primary outcome 
demonstrates a significant difference between the group using a p <0.001. 
The overall type I error rate will be preserved at 0.05.
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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Revised Template: November 10, 2014
11.2 Power Analysis: We based our power analysis on our previous work, 
literature review, and a review of recent institutional data. During the 12-
month period prior to this proposal, the rate of cesarean delivery at NMH 
was 22.4% for nulliparous women with term singletons pregnancies who 
received oxytocin prior to delivery and had fetuses in the vertex 
presentation.  For the purpose of the study design, a slightly lower rate was 
assumed for a population of women delivering at term that excluded women 
with history of prior uterine surgery and those undergoing induction of labor. 
A sample-size calculation suggests that, assuming a cesarean delivery rate 
of 20% in the traditional management LDOR group, 1002 patients (501 
patients per group) would be required for this sample to provide 80% 
power to detect a decrease in the rate of cesarean delivery to 13.4% (one-
third decrease) in the HDOR group. Chi-squared test comparing two 
independent proportions at a two-sided significance level of 0.05 is 
assumed in the power calculation.
11.3 Data Security: A Data Security Plan will be developed to ensure that 
protected health information and personally identifiable information will be 
entered, stored, transmitted, analyzed, and reported in a manner that 
maintains confidentiality.  All the members of the study investigative team 
will be included on the Authorized Personnel list of the IRB approved 
protocol; only these individuals who are authorized will be granted access to 
the research data.  All members of the study investigative team will be 
trained and certified by the Collaborative Institutional Training Initiative 
(CITI) Program.  Data integrity and confidentiality will be maintained in 
several ways.  Sources of data include patient records (electronic and 
paper), patient care providers, and subjects. All data will be collected using 
standardized data collection forms. Once all data collection forms and 
medical charts have been reviewed, all data obtained will be entered in a 
HIPAA compliant into an electronically (passwords and encryption) 
protected and secure server maintained by NUIT. All identifiers will be 
removed and patient data will be stored and archived in a de-identified 
manner.  The identifiable data will be permanently discarded by 
permanently deleting the password protected encrypted database with 
patient identifiers at the earliest opportunity. Data will be stored in 
accordance with NUIT File Sharing Policy using SharePoint and 
Northwestern file servers, which are available for storing and sharing 
sensitive research data in order to maintain confidentiality and privacy.  The 
data collected and transmitted to the central server is designed to 
strengthen de-identification and prevent any possibility of linking data to 
specific subjects.  Specifically, subject name, initials, date of birth, date of 
admission, date of delivery, date of enrollment will be removed from the 
database at the earliest opportunity.  We will organize dataset entries by 
unique subject study numbers (coinciding with drug treatment code number) 
in an anonymous manner. No patient specimens will be collected.  Only the 
principal investigator (A.M.P), co-investigators Dr. Moeun Son and Dr. 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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Bethany Stetson, andresearch assistant Dr. Archana Roy (A.R) will have 
access to data in an identifiable manner before final de-identification.
11.4 Quality Control of Collected Data: Data collection forms will be developed, 
pretested, and used by the investigators and trained clinical staff to gather 
baseline and outcome data. Investigator meetings will be held on a quarterly 
basis, including just prior to the initiation of patient enrollment.  After 
initiation of patient enrollment, investigator meetings will be held monthly for 
the first three months to discuss any questions regarding the protocol, and 
also as needed thereafter. Data will be extracted from the electronic medical 
record system, and investigators and clinical staff will remain blinded to 
group assignment during the data collection process.  Every effort will be 
made to maintain high quality data; as such, institutional resources REDCap 
and NITRO Study Tracker will be used for data entry and monitoring.  
11.5 Describe how data and specimens will be handled study-wide:
i.
Clinical data that is pertinent to the study endpoints will be extracted 
from the medical record of each subject (see ‘data collection’ form) and 
will be recorded on a standard data collection form.  Once all data 
collection forms and medical charts have been reviewed, all identifiers 
and protected health information will be removed and research data 
will be stored and archived in a de-identified manner.  The identifiable 
data will be permanently discarded by permanently deleting the 
password protected encrypted database with patient identifiers at the 
earliest opportunity.
ii.
Data will be stored in accordance with Northwestern University 
Information Technology (NUIT) File Sharing Policy using SharePoint 
and Northwestern file servers, which are available for storing and 
sharing sensitive research data in order to maintain confidentiality and 
privacy. Only the study investigators who are on the Authorized 
Personnel list of the IRB approved protocol will be granted access to 
the research data.
iii.
Research data will be retained and stored for a minimum of three years 
after the conclusion of the study as per the Northwestern University 
Policy. However, research data will be kept for as long as deemed 
necessary to protect any intellectual property resulting from the work.  
The research data will be stored and archived in a de-identified 
manner in accordance with NUIT File Sharing Policy.
iv.
Only the study investigators who are on the Authorized Personnel list 
of the IRB approved protocol will be granted access to the research 
data.
v.
The principal investigator (A.M.P.),the co-investigators Dr. Moeun Son 
and Dr. Bethany Stetson,  and research assistant (A.R.) will serve as 
custodians of the research data, and will be responsible and 
accountable for research data as it is collected, processed, stored, 
analyzed, and reported.
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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Revised Template: November 10, 2014
vi.
Data will be stored in accordance with NUIT File Sharing Policy using 
SharePoint and Northwestern file servers, which are available for 
storing and sharing sensitive research data in order to maintain 
confidentiality and privacy.
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects
12.1 Describe:
i.
The scope of risk to the patient falls under two broad categories: 1) risk 
of breaking confidentiality, and 2) risk for a significantly worse outcome 
in one study arm or the other.  Confidentiality of data will be preserved 
in multiple ways, as discussed earlier. With regard to intervention 
safety, both study arms utilize FDA-approved oxytocin at two different 
dosing rates that are both institutionally approved by protocol for the 
augmentation of labor.  Therefore, adverse events related directly to 
the drug agent oxytocin are expected to be uncommon. Furthermore, 
emergency unblinding procedures will be established to prepare for the 
event of an adverse event. This study compares two institutionally 
approved clinical oxytocin dosing protocols, and thus the need for an 
ongoing data safety and monitoring and board (DSMB) was deemed 
unnecessary. An independent review board has been established in 
the event the need for review of unexpected serious adverse event 
arises. An interim analysis was planned to be performed by an 
independent expert physician after the first 100 patients are enrolled to 
assess any safety or efficacy concerns since adjustments in the 
concentrations of the oxytocin formulations have been made in order to 
allow blinding of intervention. With regard to adverse events, the 
principal investigator (A.M.P.), co-investigators Dr. Moeun Son and Dr. 
Bethany Stetson, and research assistant (A.R.) will be empowered to 
modify or suspend the trial if they are concerned that significant harm 
has occurred due to the study protocol.  Serious adverse events 
(events felt by the investigators to be related to the dosing of oxytocin 
infusion and are life-threatening, associated with death, or specifically 
leads to increased invasive interventions) will be reported to the IRB. 
ii.
Statistical tests will be used to analyze the safety data to determine 
whether harm is occurring.  All univariate comparisons will be unpaired 
and all tests of significance will be two tailed. For univariate analysis, 
continuous variables will be compared by Student’s t-test. Categorical 
data will be compared using Chi-square testing or Fisher’s Exact Test, 
depending on sample size.  All values will be expressed as the mean + 
standard error (continuous variables) or as a percentage of the group 
from which they were derived (categorical variables). A p value of less 
than 0.05 will be considered statistically significant. The p value will not 
be adjusted for the interim analysis given its early timing. 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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Revised Template: November 10, 2014
13.0
Withdrawal of Subjects*
13.1 Subjects will be informed that they may withdraw from the study at any time 
for any reason, without prejudice to their medical care. The investigators 
also have the right to withdraw subjects from the study for the following 
reasons: non-adherence to the protocol requirements by the subject or the 
subject’s primary obstetric physician or midwife, or the subject no longer 
meets the protocol eligibility criteria (see Section 3.1 and 3.2).  Additionally, 
the study may be prematurely terminated, if in the opinion of the study co-
Principal Investigators and/o, there is sufficient reasonable cause. 
Circumstances that may warrant termination include, but are not limited to: 
failure to enroll subjects at an acceptable rate; insufficient adherence to 
protocol requirements; insufficient complete and/or evaluable data; serious 
adverse events (events felt by the investigators to be related to the dosing 
of oxytocin infusion and are life-threatening, associated with death, or 
specifically leads to increased invasive interventions). 
13.2 If a subject withdraws from the study, the primary reason for a subject’s 
withdrawal will be recorded in the data collection.  Subject who withdraw or 
are withdrawn from the study will not be replaced.  If immediate deviation 
from the protocol is required to eliminate an immediate hazard(s) to 
subjects, the investigators will contact the IRB, if circumstances permit, to 
discuss the planned course of action. Any departures from the protocol must 
be fully documented.  Unplanned protocol deviations will be reported to the 
IRB per institutional requirements.  If the opinion of the study co-Principal 
Investigators is that there is sufficient reasonable cause for premature study 
termination, written notification documenting the reason(s) for study 
termination will be provided to the both parties, and to the IRB. 
13.3 If a subject withdraws from the study, the data collected on the subject to 
the point of withdrawal will remain part of the study database and will not be 
removed. Removal of already collected data would undermine the scientific, 
and therefore the ethical, integrity of the research.  Incomplete data could 
potentially put enrolled study subjects, future study subjects, and users of 
oxytocin at unreasonable risk as a result of inaccurate data/conclusions. 
14.0
Risks to Subjects*
14.1 Currently, both dosing regimens compared in this study (LDOR and HDOR) 
are approved by established protocols for clinical practice for labor 
augmentation at NMH.  However, reasonably foreseeable risks include 
increased rates of tachysystole and cesarean deliveries performed for fetal 
heart rate tracing indications in the HDOR group, increased rates of 
maternal postpartum hemorrhage and intrauterine infections as well as 
increased cesarean deliveries performed for labor dystocia in the LDOR.  
Reasonably foreseeable inconveniences to the subjects include longer labor 
durations in the LDOR group and increased labor pain in the HDOR group.  
The protocol has been designed to minimize risks to the subjects and their 
neonates, regardless of whether they are randomized to LDOR or HDOR 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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groups.  All subjects will sign a form indicating her free and informed 
consent to participate in the study prior to randomization. Given 
randomization of dosing regimens that already have well-established safety 
profiles, we expect a low likelihood of adverse outcomes.
14.2 Investigators will be required to report any suspected or actual Unexpected 
Adverse Events (UAE) that may occur during study participation.  UAEs will 
be defined as any event that meets the following conditions: the event is not 
a known or reasonably foreseeable risk associated with the study 
procedures (e.g. risks related to administration of oxytocin and confidential 
information specified in the informed consent), and the event, in the 
investigators’ opinion, is or could be directly related to the subject’s 
participation in this research protocol.  Events that are the result of a natural 
progression of an underlying disease, disorder, condition, or a predisposing 
risk factor profile for the subject do not qualify as UAEs.  The investigators 
will be responsible for complying with IRB requirements for reporting of 
UAEs.  However, since both dosing regimens compared in this study (LDOR 
and HDOR) have already been in clinical use for labor augmentation at 
NMH, we anticipate a low likelihood of UAE.
14.3 The study will only include pregnant women (see Section 16), and thus 
potential risks to their fetuses will be considered. Several measures of 
neonatal morbidity have been predefined as safety endpoints in the study. 
However, based on prior work10 showing no increase in neonatal morbidity 
in women assigned to active management of labor using HDOR compared 
to traditional management, we anticipate no increased risks to fetuses in the 
proposed study. 
14.4 Based on the randomized nature of the study, we expect that the risk 
of discrimination based on demographic factors will be minimal.  
Subjects will only participate in the study during their hospital stay for 
labor and delivery, and thus we do not anticipate risks to others who 
are not subjects.
15.0
Potential Benefits to Subjects
15.1 There are potential direct medical benefits to individuals participating in the 
study if HDOR does in fact decrease primary cesarean delivery rates as we 
hypothesize.  This would not only prevent a surgical intervention for 
individual patients but may have positive implications for their future 
reproductive health. Furthermore, use of HDOR could potentially decrease 
rates of postpartum hemorrhage and intrauterine infection, as well as length 
of labor for individual patients.  Shortened labor durations may also have 
indirect benefits on medical care costs. 
15.2 Not applicable.
16.0
Vulnerable Populations
16.1 This research involves pregnant women, and Checklist HRP-412 has been 
reviewed. As previously discussed, scientifically appropriate clinical studies 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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Revised Template: November 10, 2014
have tested the use of different oxytocin dosing regimens, including the 
specific dosing used in the LDOR and HDOR in the proposed study. The 
risk to the fetus is caused solely by the treatment interventions that hold out 
the prospect of direct benefit for the women, and any risk is the least 
possible for obtaining the research objectives. Furthermore, only subjects 
carrying fetuses of at least 36 weeks gestation will be eligible to participate, 
which eliminates the concerns of a decision to terminate a pregnancy or 
periviability. 
17.0
Community-Based Participatory Research - Not applicable to our study
18.0
Sharing of Results with Subjects
18.1 Given the double blind nature of the study design, individual subject 
treatment assignments will remain blinded during the study, and individual 
results will not be shared with the subjects or their primary care providers. 
19.0
Setting
19.1
i.
Women who present to the NMH-PWH Obstetric Triage Unit for a chief 
complaint of “labor” or “spontaneous rupture of membranes” will be 
screened for study eligibility by a trained member of the investigative 
team when it has been determined by the primary care team that the 
patient will be admitted to the labor and delivery unit for labor 
management. Patients meeting eligibility criteria will be approached for 
potential recruitment, with the assent of their primary obstetric 
physician or midwife, once their hospital admission for a trial of labor 
has been confirmed. The study will be explained in detail and all 
questions will be answered prior to signing written informed consent to 
participate in the study. 
ii.
Once informed consent is obtained, subjects will be enrolled into the 
study if and when their primary obstetric physicians or midwives have 
determined that oxytocin infusion is to be initiated for labor 
augmentation on the labor and delivery unit.  It is at this point that 
subjects will be randomized into one of two intervention groups, as 
allocated by the NMH Investigational Pharmacy. 
iii.
Not applicable 
iv.
Not applicable
20.0
Resources Available
20.1 The principal investigator (A.M.P) is a Professor of Obstetrics and 
Gynecology and the Division Chief of Maternal Fetal Medicine at NU, and 
Chief of Obstetrics at PWH.  He is a leading expert in the antepartum and 
intrapartum management of pregnancies, particularly in the area of high-risk 
pregnancies.  He has been a PI for the Maternal-Fetal Medicine Units 
(MFMU) Network, which is funded by the National Institute of Child Health 
and Human Development (NICHD) to conduct collaborative multi-center 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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clinical trials. He has extensive experience in developing and conducting 
large-scale clinical trials in single-center and multi-center settings.  He was 
also one of the principal investigators for previous work10 at NMH using 
HDOR. The co-investigator Dr. Moeun Son is an Assistant Professor of 
Obstetrics and Gynecology at NU. She was previously the P.I. but will be 
transitioning to another institution. She will remain an Adjunct Assistant 
Professor of Obstetrics and Gynecology at NU. The co-investigator Dr. 
Bethany Stetson is an Assistant Professor of Obstetrics and Gynecology at 
NU. The research assistant (A.R) completed her residency in Emergency 
Medicine from Manipal University, India.  She is currently completing a 
Master Degree in Public Health at Northwestern University, and she will use 
part of this study for her thesis.  She is a clinical researcher at Northwestern 
University and has served as a clinical research assistant in eight 
multicenter MFMU clinical trials.  She will be applying for residency in 
Obstetrics and Gynecology next year.
20.2 Resources
i.
We are in a unique position to perform this clinical trial at NMH as both 
LDOR and HDOR protocols have been developed and validated for 
use on our Labor and Delivery Unit based on our previous work.10 
Furthermore, NMH-PWH is one of the nation’s busiest labor units with 
over 12,500 deliveries per year, which will make it feasible to achieve 
our target sample size. 
ii.
The principal investigator (A.M.P.) will be responsible for the overall 
direction and scientific conduct of this proposed study.  He will provide 
clinically relevant translation and execution of all aspects of the 
research design, patient recruitment, implementation, data analysis, 
and dissemination of findings. 
iii.
The study will be conducted in the NMH-PWH Labor and Delivery Unit 
with the cooperation of the physicians, nurses, and other care 
providers who have privileges to practice obstetrics at NMH.  The 
randomization of subjects and distribution of study medications will be 
managed by designated NMH Investigational Pharmacy staff.
iv.
Once a patient is enrolled, randomized, and in receipt of the assigned 
intervention, further clinical management will be left to the discretion of 
each patient’s care team.  However, it is important to note that NMH-
PWH has a comprehensive Labor and Delivery Unit in the case of an 
adverse event.  There is availability of a clinical obstetric staff including 
an Attending Obstetric physician as well as clinical Anesthesia staff 
including an Attending Anesthesia physician in house 24 hours a day, 
seven days a week.  There is also the availability of a highly equipped 
surgical staff, blood bank capabilities, and a pharmacy at all times. 
v.
All persons assisting with the research will undergo training in order to 
be adequately informed about the protocol prior to the start of subject 
recruitment.  All IRB-approved members of the investigative team will 
be responsible for assisting with recruitment efforts including 
participation in quarterly investigator team meetings, being advocates 
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for the study locally, and attending scientific meetings to present the 
study results when appropriate.
21.0
Prior Approvals
21.1 Approval for collaboration with the NMH Investigational Pharmacy has been 
established (see attached ‘Pharmacy letter’).  NMH has a dedicated 
Investigational Pharmacy that is a separate division of the NMH pharmacy 
department. The Investigational Pharmacy employs two research 
pharmacists and three research pharmacy technicians who are responsible 
for all research drugs for studies conducted at NMH. The Pharmacy agrees 
to randomize and dispense study medication in a blinded manner to study 
subjects.  Appropriate Pharmacy staff will be trained on the details and 
requirements of the protocol. 
22.0
Recruitment Methods
22.1 The clinical trial will be registered in a publicly accessible database 
(www.clinicaltrials.gov) before recruitment of the first subject. Potential 
subjects will be screened for study eligibility by a member of the 
investigative team using a screening script. Patients who meet eligibility 
criteria will be provided further explanation of the study. For patients who 
agree to participate, a member of the investigative team will fully explain the 
study to the subject and obtain written informed consent according to our 
institutional IRB requirements. 
22.2 All women who present to the NMH-PWH Obstetric Triage Unit and are 
admitted to the Labor and Delivery Unit for delivery will be screened for 
eligibility.
22.3 Potential subjects will be identified through the electronic patient board in 
the NMH-PWH Obstetric Triage Unit.  Potential subjects will be screened for 
study eligibility by a member of the investigative team. 
22.4 Not applicable 
22.5 Not applicable
23.0
Local Number of Subjects
We based our power analysis on our previous work, literature review, and our 
recent institutional data. During the 12-month period prior to this proposal, the 
rate of cesarean delivery at NMH was 22.4% for nulliparous women with term 
singletons pregnancies who received oxytocin prior to delivery and had fetuses in 
the vertex presentation.  For the purpose of the study design, a slightly lower rate 
was assumed for a population of women delivering at term that excluded women 
with history of prior uterine surgery and those undergoing induction of labor. A 
sample-size calculation suggests that, assuming a cesarean delivery rate of 20% 
in the traditional management LDOR group, 1002 patients (501 patients per 
group) would be required for this sample to provide 80% power to detect a 
decrease in the rate of cesarean delivery to 13.4% (one-third decrease) in the 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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HDOR group. Chi-squared test comparing two independent proportions at a two-
sided significance level of 0.05 is assumed in the power calculation.
24.0
Confidentiality
24.1 Not applicable
25.0
Provisions to Protect the Privacy Interests of Subjects
25.1 Every precaution will be taken to protect the privacy of research subjects 
and the confidentiality of their personal information to minimize the impact of 
the study on their physical, emotional, and social integrity. Confidentiality of 
data will be preserved in multiple ways, as discussed earlier.
25.2 The informed consent process will involve an extensive discussion about 
the study protocol and we will ensure that patients will feel comfortable 
about asking questions to the investigators.  We will make it clear that 
subjects will maintain the option to withdraw from the study at any time.  We 
also hope to make the subjects feel at ease with the research situation that 
both the HDOR and LDOR protocols used in our study have been 
developed and validated for use on our Labor and Delivery Unit based on 
our previous work.10
25.3 With their informed consent, we will obtain the subjects’ permission to 
access their electronic medical records during their hospital stay.  Data 
collection forms will be developed, pretested, and used by the investigators 
and trained clinical staff to gather baseline and outcome data.  Data will be 
extracted from the electronic medical record system, and investigators and 
clinical staff will remain blinded to group assignment during the data 
collection process.  Every effort will be made to maintain high quality data; 
as such, institutional resources REDCap and NITRO Study Tracker will be 
used for data entry and monitoring.
26.0
Compensation for Research-Related Injury
26.1 In the event of research-related injury, the subject will need to seek medical 
treatment through her primary obstetric physician or midwife or a treatment 
center of her choice. If she seeks treatment from someone other than the 
investigators, she will need to promptly tell the investigators about any 
related injury or illness. Generally, this care will be billed to the subject, her 
insurance, or other third party.  NMH will not pay for medical care required 
due to a research-related injury.  However, this will not prohibit subjects 
from seeking compensation for the care required due to a research-related 
injury.
26.2 Not applicable 
27.0
Economic Burden to Subjects
27.1 There will be no additional costs that the subjects will be responsible for 
because of their participation in the research.  The study has been selected 
for funding from the fiscal year 2016 Friends of Prentice Grants Initiative, for 
a total amount of $49,934 that is expected to be available by September 
IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


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2015.  This will be primarily used to cover the costs of medications and 
supplies for the subjects.  As calculated by the Pharmacy Department, the 
total cost of oxytocin IV infusion will be $46,032 for 1002 subjects x $45, 1 
vial at $0.47 x 501, 3 vials at $0.47 x 501. The projected costs include a $45 
intravenous drug dispensing fee per subject, and a drug cost of $0.47 per 
vial of oxytocin 10U.  For our sample size of 1002 subjects, 501 subjects will 
receive 1 vial of oxytocin and 501 subjects will receive 3 vials of oxytocin.  
The anticipated cost for IV tubing and drug labels is about $902 for 1002 
subjects at about $0.90 per subject. 
28.0
Consent Process
28.1 Participation by competent individuals as subjects in the study must be 
voluntary. Subjects who are interested will first be screened by an intake to 
verify that they meet the eligibility criteria. Subjects who are deemed eligible 
for study inclusion will be given a copy of the informed consent document.  
The study will be explained in detail by one of the members of the 
investigative team, and all questions will be answered prior to signing 
written informed consent to participate in the study.  Also, the patients will 
be told that they can, at any time, decline continued participation in the trial.  
Full disclosure of the nature and potential risks of participating in the trial will 
be made. 
i.
The consent process will take place in either the NMH-PWH Obstetric 
Triage Unit or the Labor and Delivery Unit.
ii.
While there will not be a pre-specified waiting time period, we will 
ensure that the prospective subject has adequate time to read over the 
informed consent document, ask any further questions, and discuss 
with family members or friends or their primary obstetric physician or 
midwife prior to signing written consent to participate. 
iii.
We will ensure that the subjects understand their option to withdraw 
from the study at any time. 
iv.
We will be following “SOP: Informed Consent Process for Research 
(HRP-090).”
Non-English Speaking Subjects 
Not applicable
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception) 
Not applicable
Subjects who are not yet adults (infants, children, teenagers)- Not 
applicable
Cognitively Impaired Adults 
Not applicable
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Adults Unable to Consent
Not applicable
Adults Unable to Consent
Not applicable
29.0
Process to Document Consent in Writing
29.1 We will be following “SOP: Written Documentation of Consent (HRP-091.” 
Please see attached ‘consent document.’ 
30.0
Drugs or Devices
30.1 Through our collaboration with the NMH Investigational Pharmacy (see 
above), the oxytocin used for our study will be stored, handled, and 
administered by authorized members of the Investigational Pharmacy staff 
who have been trained on the details and requirements of the study 
protocol.  Investigators and care teams will remain blinded to treatment 
allocation to maintain double blind study design. 
30.2 Not applicable
1.
Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of 
vital statistics: 2010-2011. Pediatrics. 2013;131(3):548-558.
2.
Liu S, Liston RM, Joseph KS, et al. Maternal mortality and severe morbidity 
associated with low-risk planned cesarean delivery versus planned vaginal delivery at 
term. CMAJ. 2007;176(4):455-460.
3.
Clark SL, Belfort MA, Dildy GA, Herbst MA, Meyers JA, Hankins GD. Maternal 
death in the 21st century: causes, prevention, and relationship to cesarean delivery. 
American journal of obstetrics and gynecology. 2008;199(1):36 e31-35; discussion 91-
32 e37-11.
4.
Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with 
multiple repeat cesarean deliveries. Obstet. Gynecol. 2006;107(6):1226-1232.
5.
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IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.


PROTOCOL TITLE: A randomized double blind clinical trial comparing oxytocin low-
dose and high-dose regimens for labor augmentation
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IRB #: STU00201148 Approved by NU IRB for use on or after 5/4/2020 through 5/3/2021.