High Dose vs. Low Dose Oxytocin for Labor Induction in Obese Women: a Randomized Controlled Trial - the OPS (Obese Pitocin Study) Trial
Phase: PHASE4
Conditions: Obesity, Labor, Induced, Oxytocin
Sponsor: University of Arizona

Cover Page 
 
High Dose vs. Low Dose Oxytocin for Labor Induction in Obese Women: a Randomized 
Controlled Trial - the OPS (Obese Pitocin Study) Trial   
 
Protocol date 04/04/2017 
 
NCT03140488 

F200: Application for Human Research 
 
 
 
 
Page 1 of 23 
 
HSPP Use Only: 
Form 200 v 2016-07 
PROJECT TITLE: 
High dose vs. Low dose oxytocin for labor induction in obese women: a 
randomized controlled trial – the OPS (Obese Pitocin Study) trial 
 
INVESTIGATOR INFORMATION 
Principal Investigator Name, 
Degree(s): 
Meghan Hill, MBBS 
Affiliation 
 UA            
 B–UMG             
Principal Investigator UA NetID 
meghanhill 
Status/Rank: 
Maternal Fetal Medicine, assistant professor 
Center: 
 College of Medicine 
Department: 
Department of Obstetrics and Gynecology, Division of 
Maternal Fetal Medicine 
College: 
University of Arizona 
Contact phone:  
5206266174 
Official Institutional Email: 
meghanhill@obgyn.arizona.edu 
 
 
ADVISOR CONTACT INFORMATION (REQUIRED FOR ALL STUDENTS AND RESIDENTS) 
Name, Degree(s), UA NetID: 
 
Contact phone:  
 
Official University Email: 
 
 
 
ALTERNATE/COORDINATOR or Co-PI CONTACT INFORMATION 
*THIS INDIVIDUAL WILL RECEIVE COPIES OF ALL CORRESPONDENCE ON THE STUDY 
Name, UA NetID: 
Co-PI: Ruth Wei, MD 
Contact phone:  
626-824-4517 
Official University Email: 
ruthwei@obgyn.arizona.edu 

 
 
 
 
 
 
 
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SECTION 1: REQUIRED SIGNATURES 
1. PRINCIPAL INVESTIGATOR 
I will conduct my study according to the University of Arizona HSPP policies and procedures for research with human 
subjects. 
 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 
 
2. ADVISOR (FOR ALL STUDENTS AND RESIDENTS ACTING AS THE PI) 
I will oversee the student researcher according to the University of Arizona HSPP policies and procedures for research with 
human subjects. 
 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 
 
3. SCIENTIFIC/SCHOLARLY REVIEW (SEE HSPP GUIDANCE ON REQUIREMENTS FOR SCIENTIFIC/SCHOLARLY ASSESSMENT  - INCLUDE 
DOCUMENTATION FOR OPTIONS A AND B WITH SUBMISSION MATERIALS.) 
a. 
 Nationally based, federal funding organization (NIH, NSF) subject to full peer review 
b. 
 Nationally based, non-federal funding organization (March of Dimes, Amer Academy of Pediatrics) subject to peer 
review 
c. 
 Locally constituted peer review (signature required)  
 
 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 
 
4. DEPARTMENT/CENTER/SECTION REVIEW 
I have reviewed this application and determined that all departmental requirements are met and that the investigator has 
adequate resources to conduct the Human Research. 
 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name/Email 
 
5. RESPONSIBLE PHYSICIAN (PROJECTS INVOLVING MEDICAL PROCEDURES WHICH THE PI IS NOT AUTHORIZED TO CONDUCT) 
I am a physician licensed by the State of Arizona (or US license for the SAVAHCS). I will be responsible for ensuring that all 
procedures that are part of this project and that require the attendance of a licensed physician will have a suitable physician 
present during the procedures. If at any time this is not possible, I will inform the IRB before any procedures are conducted. 
 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 
 
 
 

 
 
 
 
 
 
 
Page 3 of 23 
 
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SECTION 2: GENERAL INFORMATION 
1. How many Human Research studies does the PI have open? 
12 
2. How many research staff will be involved in the Human Research? 
4 
3. What is the expected length of this project?   
2-3 years 
4. Will the University of Arizona be the coordinating center for a multi-site study? 
  No   
 
 Yes- Complete Appendix C- Multi-Site study 
 
5. Retention of study materials before, during, and after completion of the project:  
a. Where will original signed consent and PHI Authorization documents be stored (building name 
and room)?  Location: Room 8237G in the Department of Obstetrics and Gynecology 
 
b. How long will consents be maintained after conclusion of the project? 
             
 6 years (UA standard)     
 6 years after child reaches 18    
 Other (explain): 
 
6. Is or will the project be funded by an external funding source e? 
  No  
 Yes- Complete below: 
 
a. Funding PI: 
b. Proposal Title:  
c. Funder Name: 
d. Total funding amount OR per subject amount: 
e. UAccess Account Information  Provide one of the following below: 
i. Institutional Proposal #: 
ii. Award #: 
 
Submit complete copy, cover-to-cover, of grant or award. If you need help locating any of the UAccess 
numbers please call Sponsored Projects at 626-6000. 
 
7. Is the project funded by a For-profit industry sponsor? 
  No  
 Yes- Complete required below: 
 
a. IRB Payment eDoc #: 
 
Please review HSPP Guidance, Fees for Human Research, for more information.  
 
8. Conflict of Interest (COI): 
The Principal Investigator hereby affirms that ALL individuals who meet the definition of 
investigator for this project in the current Policy on Investigator Conflict of Interest in Research 
have completed the mandatory Conflict of Interest training and Disclosure of Significant Financial 
Interests. 
 
 Yes  
 
 
 
 No (explain):      
  

 
 
 
 
 
 
 
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9. Additional requirements: 
Certain types of research require additional regulatory documentation. Please identify which of the 
following apply to your project. Complete the appropriate Appendix and submit as part of the 
submission materials. 
 
 Appendix A – Children (subjects under 18)  
 Appendix B – Drugs/Devices (A clinical investigation of a drug or device)  
 Appendix C – Multi-Site study (The UA IRB will review research activities for an investigator or 
research staff not affiliated with the UA who is ‘engaged in the research’ (e.g. consenting, 
collecting data, or analyzing identifiable information)  
 Appendix D – Pregnant Women/Neonates  
 Appendix E – Prisoners 
 Appendix F – Waivers of consent, waiver of a signature, or waiver or alteration of PHI 
 Appendix G – Exception From Informed Consent (EFIC)  
 Appendix H – Native American or International Indigenous populations 
 None apply to the proposed study 
 
10. Research Site: BUMG-Tucson campus 
 
Location (Explain): 
8th floor Labor and Deliver and  8OPC outpatient clinic 
 
If research is taking place at B–UMG or AZCC please check the appropriate boxes below: 
 
Banner – University Medicine Group: 
 Phoenix Campus 
 
 
 
 Biological specimens 
 Clinical Data 
 Tucson Campus      
 
 
 
 Biological specimens 
 Clinical Data 
 South Campus  
 
 
 
 Biological specimens 
 Clinical Data 
*Submit a copy of the UAHS Research feasibility review approval 
 
University of Arizona Cancer Center: 
 North Campus  
 
 
 
 Biological specimens 
 Clinical Data 
 Orange Grove Clinics   
 
 
 Biological specimens 
 Clinical Data 
 Phoenix 
 
 
 
 
 Biological specimens 
 Clinical Data 
*Submit a copy of the Scientific Review Committee letter 
 
 
 
SECTION 3.  PROJECT NARRATIVE 
1) Background 
The obesity epidemic 
Obesity has become an epidemic in the first world countries. Obesity is defined by BMI ≥30. Within 
obesity, class I, II, III obesity are defined by BMI between 30-34.9, 35-39.9, and ≥40 respectively. 
According to the Institute of Medicine Guidelines in 2009, over 30% of women of childbearing age in 
the United States are obese. Obesity is far more common among racial or ethnic minority groups, 

 
 
 
 
 
 
 
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with only 23% of African American women in the normal weight category. The prevalence of class I 
obesity in African American women approaches 25%, and the prevalence of class II and III obesity 
each exceed 10% 1. In addition to the usual health complications, there are consistent clinical data to 
support that obesity in pregnancy is an independent risk factor for multiple complications in 
pregnancy during antenatal, intrapartum, delivery and postpartum periods 2.  
Complications of obesity in pregnancy 
Specifically, obesity in pregnancy is associated with a higher chance of induction of labor, failed 
induction of labor, longer induction, and a higher rate of cesarean delivery 3-12. Obese patients are 
more likely to undergo induction secondary to medical comorbidities, including pregnancy related 
hypertension and diabetes. They are also less likely to go into spontaneous labor resulting in late 
term pregnancy and induction of labor. When obese women undergo induction, they are more likely 
to fail their induction or have labor dystocia resulting in a higher cesarean delivery rate, reportedly 
up to 50-60% (compared to the national overall cesarean delivery rate of 30%). In patients 
undergoing a cesarean delivery during labor induction, obese pregnant women are more likely to 
have their procedures during the first stage of labor (83% vs. 61%, aOR 2.87 [1.35-6.1]). Obese 
patients are also more likely to undergo cesarean delivery secondary to failure to progress or labor 
dystocia (22% vs. 12%, p = 0.01) 8,13. Trends in clinical management may also disproportionately 
affect obese women due to their prolonged labors. Cesarean delivery in obese patients has its 
unique set of intraoperative challenges and postoperative complications including prolonged 
operative times, wound breakdown, infection, and venous thromboembolism 2. Identifying potential 
etiologies and interventions to this clinical challenge will decrease morbidity and improve pregnancy 
outcomes in this population. 
Physiology of parturition and oxytocin pharmacokinetics 
To decipher the problem with prolonged induction and labor dystocia in the obese cohort, we need 
to first discuss the normal physiology of parturition and oxytocin pharmacokinetics. In normal 
pregnancy, the placenta, cervix, amnion and myometrium of the uterus all work in a synergistic 
fashion to prepare for labor 14. An increase in oxytocin receptors in the myometrium and its 
sensitivity to the oxytocin hormone are keys to initiation of labor 15. Oxytocin is an endogenous 
hormone synthesized from the hypothalamus and secreted by posterior pituitary gland. The 
synthetic analog, Pitocin, is widely used on every labor and delivery for induction of labor. An 
infusion of oxytocin reaches a steady state at 30-40 minutes based on the plasma clearance rate 16. 
The half-life for oxytocin is about 4.5 minutes 17,18.  
Obesity: a unique parturition phenotype 
Biological evidences linking obesity and labor dystocia are largely unknown and currently under 
investigation. Obesity-related changes in the hormonal milieu seem linked to labor dysfunction. 
Various obesity related hormones, called “adipokines”, are hypothesized to alter the normal 
parturition physiology in the obese cohorts and have an inhibitory effect on oxytocin stimulated 
myometrial contractions. Oxytocin receptors are also found to be decreased in numbers and 
responsiveness in myometrial biopsies in obese cohorts, however existing evidence is currently weak 
14. Specific mechanisms remain unknown.  
More oxytocin requirement in obese patients 
While the underlying pathophysiology is still currently unknown, there are known correlations with 
obesity and increased oxytocin requirement. Currently, a standard low dose oxytocin regimen is 

 
 
 
 
 
 
 
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typically used regardless of the BMI of the patient in the United States. While most of the United 
States uses the low dose protocol, ACOG (The American College of Obstetricians and Gynecologists) 
states that both the high and low dose protocols are appropriate for labor induction and each 
hospital’s department should develop their own guidelines. Per the ACOG practice bulletin on 
induction of labor, low dose oxytocin protocol consists of starting at 0.5-2miliunit/min, increasing by 
1-2miliunit/min, at an interval of every 15-40 minutes 19. A high dose oxytocin protocol which is also 
endorsed by the ACOG practice bulletin, consists of starting at 6miliunit/min, increasing by 3-
6miliunit/min, at an interval of every 15-40 minutes. Furthermore, emerging evidences suggest that 
obese patients may require more oxytocin to achieve labor progression 8,20,21. Three studies have 
specifically evaluated the total amount of oxytocin used during the first stage of labor in the obese 
cohort. They found that a statistically higher amount of oxytocin was needed to achieve vaginal 
delivery compared to the lean cohort. The principal investigator, Dr Hill, performed her work at the 
University of Arizona, indicating that this finding applies to this patient population.  
Safety of high dose oxytocin protocols 
Many randomized controlled trials had previously compared various high and low dose oxytocin 
protocols and demonstrated safety of both protocols. Meta-analyses including a Cochrane review in 
2014 confirmed the safety and utility of high and low dose oxytocin protocols 22-24. While there were 
no significant differences in rates of vaginal delivery or cesarean delivery, there was also no 
difference in serious maternal or neonatal morbidity or death. The Cochrane review as well as the 
meta-analysis found a statistically significant reduction in time to delivery in the high dose oxytocin 
group. Otherwise, there were no differences in adverse outcomes, including maternal uterine 
rupture, postpartum hemorrhage, endometritis, estimated blood loss, abnormal fetal heart tracing, 
fetal Apgar, newborn resuscitation and neonatal intensive care unit admission.  
There were case reports originating from the 1970s about concerns over high dose oxytocin and its 
association with maternal hyponatremia or water intoxication 25,26. The hypothesis behind its 
association is due to the similarity between oxytocin and anti-diuretic hormone. These were largely 
single case reports in the setting of accidental large overdose of oxytocin in addition to 
administration of large volumes of electrolyte-free solutions. Since then, the practice of 
administering oxytocin is only given alongside isotonic lactated ringer or normal saline in a slow 
intravenous infusion fashion 27,28. In addition, there were also some case series showing that a large 
amount of oxytocin given intravenously as a bolus can cause maternal hypotension, tachycardia and 
EKG changes 29,30. In a similar fashion, these changes were observed due to a very large amount of IV 
boluses given over a short amount of time, which is a very different practice than how oxytocin is 
now administered on labor and delivery via a slow intravenous infusion. 
1. IOM (Institute of Medicine) and NRC (National Research Council). 2009. Weight Gain During Pregnancy: Reexamining 
the Guidelines. Washington, DC: The National Academies Press. 
2. Obesity in pregnancy. Practice Bulletin No. 156. American college of obstetricians and gynecologists. Obstet Gynecol 
2015; 126:e112-26.  
3. Carlson et al. Parturition dysfunction in obesity: time to target the pathobiology. Reproductive and endocrinology 
(2015) 13:135. 
4. Dietz PM, Callaghan WM, Morrow B, Cogswell ME. Population-based assessment of the risk of primary cesarean 
delivery due to excess pre-pregnancy weight among nulliparous women delivering term infants. Matern child health 
J. 2005; 9:237-44.  
5. Arrowsmith S, Wray S, Quenby S. Maternal obesity and labour complications following inuction of labour in 
prolonged pregnancy. BJOG. 2011; 118:578-88.  

 
 
 
 
 
 
 
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6. Kominiarek M, Zhang J, VanVeldhuisen P, Troendle J, Beaver J, Hibbard JU. Contemporary labor patterns: the impact 
of maternal body mass index. Am J Obstet Gynecol. 2011; 205:244.e241-8. 
7. Norman SM, Tuuli MG, Odibo Ao, Caughey AB, Roehl KA, Cahill AG. The effects of obesity on the first stage of labor. 
Obstet Gynecol. 2012; 120:130-5 
8. Pevzner L, Powers BL, Rayburn WF, Rumney P, Wing DA. Effects of maternal obesity on duration and outcomes of 
prostaglandin cervical ripening and labor induction. Obstet Gynecol. 2009; 114: 1315-21.  
9. Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, Saade G, Eddleman K, Carter SM, Craigo SD, Carr SR, 
D’alton ME; FASTER research consortium. Obesity, obstetric complications and cesarean delivery rate – a 
population-based screening study. Am J Obstet Gynecol. 2004 Apr; 190(4): 1091-7. 
10. Robinson B, et al. Increasing maternal body mass index and characteristics of the second stage of labor. For the 
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the Maternal-Fetal 
Medicine Units Network (MFMU). Obstet Gynecol. 2011 Dec; 118(6); 1309-1313.  
11. Fye EM et al. Screening for Pregnancy Endpoints Consortium (SCOPE). Risk of first-stage and second-stage cesarean 
delivery by maternal body mass index among nulliparous women in labor at term. Obstet Gynecol. 2011 Jun; 117(6): 
1315-22.  
12. Vahratian et al. Maternal prepregnancy overweight and obesity and the pattern of labor progression in term 
nulliparous women. Obstet Gynecol. 2004 Nov; 104(5): 943-951. 
13. Verdiales M, Pacheco C, Cohen W. The effect of maternal obesity on the course of labor. J. Perinat. Med. 37 (2009) 
651-655. 
14. Carlson NS, Hernandez TL, Hurt KJ. Parturition dysfunction in obesity: time to target the pathobiology. Reproductive 
biology and endocrinology (2015) 13:135. 
15. Fuchs AR, Fuchs F, Husslein P, Soloff M, and Fernstrom MJ. Oxytocin receptors and human parturition: a dual role for 
oxytocin in the initiation of labor. Science, New series vol 215, No 4538. Mar 12, 1982. 1396-1398. 
16. Seitchik, J, Amico J, Robinson AG, Castillo M. Oxytocin augmentation of dysfunctional labor. AM J Obstet Gynecol 
1984; 150: 225-8. 
17. Thornton S, Davison J, Baylis P. Plasma oxytocin during the first and second stages of spontaneous human labour. 
Acta Endocrinologica 1992, 126: 425-9. 
18. Hayes EJ, Weinstein L. Improving patient safety and uniformity of care by a standardized regimen for the use of 
oxytocin. Am J Obstet Gynecol 2008; 198:622.e1-622.e7. 
19. Induction of labor. ACOG Practice Bulletin No.107. American College of Obstetricians and Gynecologists. Obstet 
Gynecol 2009; 114: 386-397. 
20. Hill M, Reed KL, Cohen WR. Oxytocin utilization for labor induction in obese and lean women. J. Perinat. Med. 2015 
Nov;43(6): 703-6. 
21. Roloff K, Peng S, Sanchez-Ramos L, Valenzuela GJ. Cumulative oxytocin dose during induction of labor according to 
maternal body mass index. Int J Gynaecol Obstet. 2015 Oct; 131 (1): 54-8. 
22. Wei SQ, Luo ZC, Qi HP, Xu H, Fraser WD. High dose vs. low dose oxytocin for labor augmentation: a systematic 
review. Am J Obstet Gynecol 2010 Oct; 203(4): 296-304.  
23. Zhang J, Branch DW, Ramirez MM, Laughon SK, Reddy U, Hoffman M, Bailit J, Kominiarek M, Chen Z, Hibbard JU. 
Oxytocin regimen for labor augmentation, labor progression, perinatal outcomes. Obstet Gynecol 2011 Aug; 118 (2 
Pt 1):249-56. 
24. Budden A, Chen LJY, Henry A. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term. 
Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD009701.  
25. Jensen I, Bruns BJ. Water intoxication after oxytocin-induced midtrimester abortion. NZ Med J. 1979 April 25; 
89(634):300-2. 
26. Lauersen NH, Birnbaum SJ. Water intoxication associated with oxytocin administration during saline-induced 
abortion. Am J Obstet Gynecol. 1975 Jan 1; 121(1): 2-6. 

 
 
 
 
 
 
 
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27. Higgins J, Gleeson R, Holohan M, Coone C, Darling M. Maternal and neonatal hyponatremia: a comparison of 
Hartmanns solution with 5% dextrose for the delivery of oxytocin in labor. European Journal of Obstetrics and 
Gynecology and Reproductive Biology 68 (1996) 47-48. 
28. Moen V, Burdin L, Rundgren M, Irestedt L. Hyponatremia complicating labor – rare or unrecognized? A prospective 
observational study. BJOG 2009; 116: 552-561. 
29. Svanstrom MC, Biber B, Hanes M, Johansson G, Naslund U, Balfors EM. Signs of myocardial ischemia after injection 
of oxytocin: a randomized double-blinded comparsion of oxytocin and methylergometrine during cesarean section. 
British Journal of Anaesthesia 100 (5): 683-9 (2008). 
30. Bhattacharya S, Ghosh S, Ray D, Mallik S, Laha A. Oxytocin administration during cesarean delivery: randomized 
controlled trial to compare intravenous bolus with intravenous infusion regimen. J Anaesthesiol Clin Pharmacol. 
2013 Jan-Mar; 29(1): 32-35. 
2) Purpose 
The objective of this study is to compare high and low dose oxytocin in obese and lean gravida and 
their effect in length of time to delivery. The hypothesis is that high dose oxytocin will decrease time 
to delivery in full term obese cohort undergoing an induction of labor and that their labor cures will 
more closely approximate those of lean patients. This study is a double blinded randomized 
controlled trial with an intention to treat analysis.  
4 Comparison groups: 
1) Control group: Lean cohort: BMI ≤25, at <20 weeks gestation or BMI ≤28 at a term gestation, low 
dose oxytocin protocol 
2) Intervention group: Lean cohort: BMI ≤25, at <20 weeks gestation or BMI ≤28 at a term 
gestation, high dose oxytocin protocol 
3) Control group: Obese cohort: BMI ≥30, at <20 weeks gestation or BMI ≥35 at a term gestation, 
low dose oxytocin protocol 
4) Intervention group: Obese cohort: BMI ≥30, at <20 weeks gestation or BMI ≥35 at a term 
gestation, high dose oxytocin protocol 
Primary outcome: Length of time to delivery (number of minutes from induction of labor to 
delivery). In case of cesarean delivery, length of time to delivery will be calculated from start time of 
induction to time when decision was made to proceed with cesarean delivery.  
Secondary outcomes: 
Length of time in 1st stage and 2nd stage of labor 
Total amount of oxytocin, median, mean, and maximum oxytocin rate 
Terbutaline use 
Rate of cesarean delivery, and rate of cesarean delivery for labor arrest 
Maternal and neonatal complications including, postpartum hemorrhage, uterine rupture, 
tachysystole, chorioamnionitis, abnormal fetal heart tracing, fetal Apgar, neonatal intensive care unit 
admission rate, cord gas 
3) Lay Summary (approximately 400 words) 
Obesity is considered one of the biggest public health concern of the 21st century and increases the 
risk of many comorbid medical conditions. Obesity in pregnancy places women at higher risk of 

 
 
 
 
 
 
 
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obstetrical complications during pregnancy, delivery and postpartum. In particular, obese pregnant 
women have more difficulty going into labor, a longer labor course, and even with pharmacologic 
treatment, have a higher chance of requiring cesarean delivery.  
When pregnant women need help going into labor, they commonly receive a medication called 
Pitocin on the labor and delivery floor. Pitocin is the brand name and is a synthetic analog to the 
naturally produced oxytocin, a hormone secreted by mother when they naturally go into labor. This 
medication has been used widely around the world. There is emerging evidence that obese women 
need more oxytocin to go into labor compared to their lean cohorts. There are many studies to 
support the use of different oxytocin dosages and are currently supported by the American College 
of Obstetricians and Gynecologists. Despite these evidences, a low dose oxytocin regimen is 
universally used in the United States, regardless of patient characteristics. 
This study is a double blinded randomized controlled trial. Both lean and obese cohorts will be 
recruited for the study. We will randomly place both cohorts into the low or the high dose oxytocin 
regimen treatment group. The investigators, patients and providers will be blinded and will not know 
the specific assignments. The purpose of this study is to evaluate the effect of high dose oxytocin in 
the obese cohort. The hypothesis is that obese patient will have shorter time to delivery with the 
high dose oxytocin regimen without incurring any additional risks or adverse outcomes.  
4) Setting of the Human Research 
Recruitment and conduct of research for eligible patients will take place at the 8OPC/outpatient OB 
GYN clinic and the inpatient Labor and Delivery unit at the Banner University Medical Center.  
5) Resources available to conduct the Human Research  
The facility and resources at the outpatient 8OPC/OB GYN clinic and the inpatient labor and delivery 
unit at the Banner University Medical Center will be utilized to carry out this research study. This 
include 14 clinical rooms in the outpatient setting; 12 labor beds, 8 triage beds, and more than 20 
postpartum beds in the inpatient setting. Both sites are staffed by 16 resident physicians, 3 maternal 
fetal medicine fellows, as well as attending physicians affiliated with the University of Arizona at 
their regular business hours. Additionally, both sites are fully supported by nursing and other clinical 
staffs. There are always 24 hours nursing and in house physician care in the inpatient setting.  
The department of statistics will be asked to provide a randomization sequence for the lean patients 
and a separate sequence for the obese patient to be enrolled in the trial. The lists will be provided to 
the research pharmacy. The research pharmacy will be responsible for creating the different 
concentrations of oxytocin infusion drugs which will be labeled as “OPS drug” (Obese Pitocin Study). 
They will also be responsible for the allocation concealment and blinding aspect of the randomized 
controlled trial. Bags of oxytocin infusion will appear identical but will contain either low dose or 
high dose concentrations. The bags will be labelled with study number only (the pharmacist 
preparing the bags will be the only person able to access the information on study allocation via 
their list). 
The principal investigator, Dr. Meghan Hill, Co-PI, Dr. Ruth Wei, the research coordinator, Destiny 
Dicken, and any other research staffs included in the VOTF will complete the recruitment and 
consent portion of this study. Recruitment and consent can take place both in the outpatient and 
inpatient facilities. All physicians included on the VOTF form will carry out the study on the inpatient 
unit. The nurses and physicians assigned to the patient will carry out their routine clinical duties.  

 
 
 
 
 
 
 
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The nursing staff, resident physicians and the attending physicians will have a meeting with Dr. Ruth 
Wei to go over the protocol of the study to minimize errors, confounding biases, drop outs, and 
improve protocol adherence. Nursing and physician roles will not change, but the investigator will 
facilitate the understanding of this study with the staff.  
Otherwise, no additional training is required, as administering oxytocin is a daily activity on the labor 
and delivery unit. 
6) Study Population 
Term pregnant women over 37 weeks admitted to labor and delivery undergoing induction of labor 
at Banner University Medical Center will be recruited for this study.  
Using the data from a previous retrospective study performed in this institution1, the average time of 
the first stage of labor in the obese cohort was 895 minutes. The average time of first stage of labor 
in the lean cohort was 660 minutes, with a standard deviation of 330 mins. At alpha of 0.05, and 
power of 80%, to decrease time to delivery in a similar fashion above (30% reduction), from 895 
minutes to 660 minutes, we would need 31 patients in each group.  
The investigator plans to enroll a total of 35 patients in each of the 4 groups. The projected total 
sample size will be 140. We anticipate a low risk of loss to follow up as patients are admitted for 
delivery and data will only be collected during their hospital stay. Withdrawals and protocol 
deviations will be included into the data analysis in all groups as this study is an intention to treat 
analysis. We anticipate a low withdrawal rate after enrollment and randomization. We will delay 
randomization until when patient is ready to receive study drug to minimize withdrawal rate. 
Inclusion criteria: 
Singleton pregnancy ≥ 37 weeks gestation 
Patient presented for induction of labor who is determined to be a candidate for oxytocin 
Cephalic presentation 
Reassuring fetal health assessment (no abnormal findings in fetal assessment, see below) 
 
The requirement for fetal health assessment for determining candidacy for oxytocin would be no 
different in a study patient than in a non-study patient.  
Meeting one of the following BMI category:  
 
Obese group: BMI ≥30 at <20 weeks of pregnancy, or BMI ≥35 at a term gestation of pregnancy 
 
Lean group: BMI ≤25 at <20 weeks of pregnancy, or BMI ≤28 at a term gestation of pregnancy 
Exclusion criteria: 
Non-reassuring fetal assessment at the time of recruitment 
Positive Contraction Stress Test - late decelerations after 50% or more of contractions 
Category III fetal heart tracing  
Prolong bradycardia or fetal deceleration 
Biophysical profile <4/10 
Reverse end diastolic flow of the umbilical artery Doppler  

 
 
 
 
 
 
 
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Previous cervical ripening agents (cytotec, cervidil, cervical Foley Balloon) 
<18 years of age 
Prisoners 
Any patients contraindicated for vaginal delivery 
Multiple gestations 
History of previous cesarean delivery 
Patients with history of significant cardiac disease 
Fetal demise 
Estimated fetal weight greater than 4500 grams in diabetic and 5000 grams in non-diabetic mother 
Ruptured membranes 
Spontaneous labor (latent or active phase) 
Augmentation of labor (latent or active phase) 
1. Hill M, Reed KL, Cohen WR. Oxytocin utilization for labor induction in obese and lean women. J. Perinat. Med. 2015 
Nov;43(6): 703-6. 
7) Recruitment Methods and Consenting Process 
a. Recruitment Process: Potential subjects will be identified through the daily census on labor and 
delivery as well as through the daily clinic schedule at 8OPC/OB GYN clinic (see Appendix F for 
partial PHI waiver). Recruitment and consent will take place on both labor and delivery unit as 
well as the outpatient OB/GYN clinic. The recruitment and consent will occur during regular 
business hours of both locations. There will be no recruitment material in addition to the 
required informed consent. The study staff will complete the recruitment and consent portion of 
this study. Though there is not a script that the study staff will read out to the patient, the 
sections of the consent form will be used as a guide for discussion with the patients before study 
procedures are undertaken. All questions will be answered to study subject’s satisfaction. The 
study will only be performed after the study consent is signed.  
It is possible that previously eligible and consented patients will become ineligible when they 
present to labor and delivery, because they could have gone into labor on their own or rupture 
their membrane prior to presentation to labor and delivery. In this case, the patient will be 
considered a screen failure.  
b. Informed Consent: The consent process was described above. All consent will be documented in 
written format. It will be communicated to the patients that there will be no change in their 
clinical care, regardless if patient agreed to consent with this study. For example, participation in 
this study does not affect the options for pain management during labor routinely available to 
the patient. This will minimize the potential for coercion. Patients who decline enrollment in the 
trial will have the method of induction chosen by their physician. Additionally, as this study is an 
induction of labor study, patients will be recruited and consented prior to going into labor so that 
the consent process is not completed under stress.  
8) Research procedures involved in the Human Research 
Sequence generation for randomization, Allocation method and Blinding 

 
 
 
 
 
 
 
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This portion of the study will be carried out by the research pharmacy. Single (low dose) and triple 
(high dose) concentration of oxytocin will be premixed in the intravenous fluid bag in the pharmacy. 
Sequence generation for randomization will be created with 1:1 ratio in both the obese and lean 
group by the Department of Statistics. After the sequence is generated, this list will be given to the 
research pharmacy. The premixed oxytocin medication will be sequentially labelled as “OPS drug, 
patient #1, 2, 3” etc. per the allocation. Allocation concealment will also be carried out by pharmacy 
as these bags will completely appear identical after they are labelled numerically. Once a patient is 
randomized, the pharmacy will send up the appropriate concentration of oxytocin already premixed 
in the intravenous fluid bag, labelled as “OPS drug, patient #”. Lean group will be assigned at # 1-70 
and obese group will be assigned at #71-140. 
Through the above process, the concentration of the drug will be blinded to the investigators, 
providers, patient and analysts. The patient will continue to have the same concentration of oxytocin 
until delivery.  
Study Drug (please see appendix B) 
Low dose oxytocin regimen (the standard at Banner University Labor and Delivery, as well as across 
the United States): 30 units in 500cc 0.9% normal saline bag (60 miliunit/cc). Starting rate would be 2 
miliunit/minute, or 2cc/hour. The medication will be increased by 2 miliunit/minute = 2cc/hr every 
30 minutes until adequacy of contraction or cervical change. At 20 miliunit/minute = 20cc/hr, 
provider will assess patient for eligibility to continue to increase oxytocin dosage.  
High dose oxytocin regimen (endorsed by American College of Obstetricians and Gynecologists): 90 
units in 500cc 0.9% normal saline bag (180 miliunit/cc). Starting rate would be 6 miliunit/minute, or 
2cc/hour. The medication will be increased by 6 miliunit/minute = 2cc/hr every 30 minutes until 
adequacy of contraction or cervical change. At 60 miliunit/minute = 20cc/hr, provider will assess 
patient for eligibility to continue to increase oxytocin dosage.  
Patient recruitment, enrollment and entering randomization 
Pregnant women at ≥ 37 weeks presented to labor and delivery for induction of labor meeting the 
inclusion criteria with no exclusion criteria as stated above will be approached for recruitment and 
enrollment into this study. As stated previously, patients can be recruited and consented from the 
outpatient clinic as well. The study staff will provide informed consent to all patients. Risk and 
benefits of the study will be explained to each eligible patient.  
After the consent is obtained, patient will enter the randomization process when they are ready to 
receive oxytocin for their induction of labor. The investigator will inform the research pharmacy if 
the patient should be in the lean or obese cohort. The research pharmacy will then assign the next 
allocation (already pre-determined by the sequence allocation as detailed above) and send the 
appropriate medication to the 8th floor L&D. The research pharmacy will track the study allocations. 
There are 4 comparison group: 
1. Control group: Lean cohort: BMI ≤25, at <20 weeks gestation or BMI ≤28 at a term gestation 
of pregnancy, low dose oxytocin protocol 
2. Intervention group: Lean cohort: BMI ≤25, at <20 weeks gestation or BMI ≤28 at a term 
gestation of pregnancy, high dose oxytocin protocol 
3. Control group: Obese cohort: BMI ≥30, at <20 weeks gestation or BMI ≥35 at a term 
gestation of pregnancy, low dose oxytocin protocol 

 
 
 
 
 
 
 
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4. Intervention group: Obese cohort: BMI ≥30, at <20 weeks gestation or BMI ≥35 at a term 
gestation of pregnancy, high dose oxytocin protocol 
Lean cohorts will be randomized into the low dose or high dose oxytocin arm. The obese cohorts will 
also be randomized into the low dose or high dose oxytocin arm.  
Protocol for each comparison group 
Management of oxytocin induction in this study follows normal standard of care on labor and 
delivery nationally. The only part which will be done specifically for research is the higher 
concentration of oxytocin given in this study in the high dose oxytocin arm.  
Per routine care, oxytocin dosage is titrated up or down to achieve labor while maintaining patient 
safety. Patient safety is continuously monitored with the tocometer (to monitor for maternal uterine 
contractions) and fetal heart tracing (to monitor for fetal well being). Stopping rules are listed under 
each arm separately.  
1) Lean, low dose oxytocin arm 
Oxytocin will be administered as described above via a slow intravenous infusion pump. Under 
the supervision of the study investigator, the patient’s nurse will increase the oxytocin infusion 
as described above, start at 2cc/hr, increase 2cc/hr every 30 minutes up to 20cc/hr. The oxytocin 
will be increased until one of the parameters below were met: 
 
>200 Montevideo unit on an intrauterine pressure catheter 
3-5 uterine contractions in a 10-minute period on the external uterine tocometer 
cervical change and progression of labor 
Tachysystole is defined as more than 5 contractions in 10 minutes over an average of a 30 
minutes period. In the setting of tachysystole with reassuring fetal status, the oxytocin would be 
decreased by increments of 2cc until tachysystole no longer occurs. In the setting of 
nonreassuring fetal status (determined by the provider based on the fetal heart tracing), the 
oxytocin infusion would be turned off and restarted at ½ of the previous dose after 30 minutes, 
as long as fetal heart tracing recovers.  
Similarly, regardless of tachysystole, if nonreassuring fetal status occur (at the discretion by the 
provider), the oxytocin infusion will be turned off and restarted at ½ of the previous dose after 
30 minutes, as long as fetal heart tracing recovers. If fetal heart tracing does not recover, the 
general protocol on labor and delivery would generally warrant an expedited delivery via 
cesarean delivery. This decision will be made at the discretion of the provider. Therefore, 
cesarean delivery and operative vaginal delivery is reserved for the usual indications determined 
by the provider.  
Monitoring of maternal urine output is routinely done on labor and delivery every 4 hours. If 
oliguria occurs (<0.5cc/kg/hour), a basic metabolic panel will be obtained to assess for 
hyponatremia. If the sodium level is below 130 meq/L, the oxytocin infusion will be turned off 
until resumption of urine output or rise in sodium level to above 130meq/L.  
Patient will remain in nothing per oral status per routine guidelines on labor and delivery. Patient 
can receive other common obstetrical intervention per usual, including epidural placement for 
pain control, artificial rupture of membrane for labor progression, internal intrauterine pressure 

 
 
 
 
 
 
 
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catheter or fetal scalp electrode placement for closer monitoring. Similarly, management of 2nd 
stage of labor after achieving full cervical dilation will be managed per routine care.  
Subsequently after delivery, a new bag of usual concentration of oxytocin will be used in all 4 
groups for postpartum oxytocin as per routine.  
2) Lean, high dose oxytocin arm 
Oxytocin will be administered as described above via a slow intravenous infusion pump. Under 
the supervision of the study investigator, the patient’s nurse will increase the oxytocin infusion 
as described above, start at 2cc/hr, increase 2cc/hr every 30 minutes up to 20cc/hr. The oxytocin 
will be increased until one of the parameters below were met: 
 
>200 Montevideo unit on an intrauterine pressure catheter 
3-5 uterine contractions in a 10-minute period on the external uterine tocometer 
cervical change and progression of labor 
Tachysystole is defined as more than 5 contractions in 10 minutes over an average of a 30 
minutes period. In the setting of tachysystole with reassuring fetal status, the oxytocin would be 
decreased by increments of 2cc until tachysystole no longer occurs. In the setting of 
nonreassuring fetal status (determined by the provider based on the fetal heart tracing), the 
oxytocin infusion would be turned off and restarted at ½ of the previous dose after 30 minutes, 
as long as fetal heart tracing recovers.  
Similarly, regardless of tachysystole, if nonreassuring fetal status occur (at the discretion by the 
provider), the oxytocin infusion will be turned off and restarted at ½ of the previous dose after 
30 minutes, as long as fetal heart tracing recovers. If fetal heart tracing does not recover, the 
general protocol on labor and delivery would generally warrant an expedited delivery via 
cesarean delivery. This decision will be made at the discretion of the provider. Therefore, 
cesarean delivery and operative vaginal delivery is reserved for the usual indications determined 
by the provider.  
Monitoring of maternal urine output is routinely done on labor and delivery every 4 hours. If 
oliguria occurs (<0.5cc/kg/hour), a basic metabolic panel will be obtained to assess for 
hyponatremia. If the sodium level is below 130 meq/L, the oxytocin infusion will be turned off 
until resumption of urine output or rise in sodium level to above 130meq/L.  
Patient will remain in nothing per oral status per routine guidelines on labor and delivery. Patient 
can receive other common obstetrical intervention per usual, including epidural placement for 
pain control, artificial rupture of membrane for labor progression, internal intrauterine pressure 
catheter or fetal scalp electrode placement for closer monitoring. Similarly, management of 2nd 
stage of labor after achieving full cervical dilation will be managed per routine care.  
Subsequently after delivery, a new bag of usual concentration of oxytocin will be used in all 4 
groups for postpartum oxytocin as per routine.  
3) Obese, low dose oxytocin arm 
Oxytocin will be administered as described above via a slow intravenous infusion pump. Under 
the supervision of the study investigator, the patient’s nurse will increase the oxytocin infusion 
as described above, start at 2cc/hr, increase 2cc/hr every 30 minutes up to 20cc/hr. The oxytocin 
will be increased until one of the parameters below were met: 

 
 
 
 
 
 
 
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>200 Montevideo unit on an intrauterine pressure catheter 
3-5 uterine contractions in a 10-minute period on the external uterine tocometer 
cervical change and progression of labor 
Tachysystole is defined as more than 5 contractions in 10 minutes over an average of a 30 
minutes period. In the setting of tachysystole with reassuring fetal status, the oxytocin would be 
decreased by increments of 2cc until tachysystole no longer occurs. In the setting of 
nonreassuring fetal status (determined by the provider based on the fetal heart tracing), the 
oxytocin infusion would be turned off and restarted at ½ of the previous dose after 30 minutes, 
as long as fetal heart tracing recovers.  
Similarly, regardless of tachysystole, if nonreassuring fetal status occur (at the discretion by the 
provider), the oxytocin infusion will be turned off and restarted at ½ of the previous dose after 
30 minutes, as long as fetal heart tracing recovers. If fetal heart tracing does not recover, the 
general protocol on labor and delivery would generally warrant an expedited delivery via 
cesarean delivery. This decision will be made at the discretion of the provider. Therefore, 
cesarean delivery and operative vaginal delivery is reserved for the usual indications determined 
by the provider.  
Monitoring of maternal urine output is routinely done on labor and delivery every 4 hours. If 
oliguria occurs (<0.5cc/kg/hour), a basic metabolic panel will be obtained to assess for 
hyponatremia. If the sodium level is below 130 meq/L, the oxytocin infusion will be turned off 
until resumption of urine output or rise in sodium level to above 130meq/L.  
Patient will remain in nothing per oral status per routine guidelines on labor and delivery. Patient 
can receive other common obstetrical intervention per usual, including epidural placement for 
pain control, artificial rupture of membrane for labor progression, internal intrauterine pressure 
catheter or fetal scalp electrode placement for closer monitoring. Similarly, management of 2nd 
stage of labor after achieving full cervical dilation will be managed per routine care.  
Subsequently after delivery, a new bag of usual concentration of oxytocin will be used in all 4 
groups for postpartum oxytocin as per routine.  
4) Obese, high dose oxytocin arm 
Oxytocin will be administered as described above via a slow intravenous infusion pump. Under 
the supervision of the study investigator, the patient’s nurse will increase the oxytocin infusion 
as described above, start at 2cc/hr, increase 2cc/hr every 30 minutes up to 20cc/hr. The oxytocin 
will be increased until one of the parameters below were met: 
 
>200 Montevideo unit on an intrauterine pressure catheter 
3-5 uterine contractions in a 10-minute period on the external uterine tocometer 
cervical change and progression of labor 
Tachysystole is defined as more than 5 contractions in 10 minutes over an average of a 30 
minutes period. In the setting of tachysystole with reassuring fetal status, the oxytocin would be 
decreased by increments of 2cc until tachysystole no longer occurs. In the setting of 
nonreassuring fetal status (determined by the provider based on the fetal heart tracing), the 
oxytocin infusion would be turned off and restarted at ½ of the previous dose after 30 minutes, 
as long as fetal heart tracing recovers.  

 
 
 
 
 
 
 
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Similarly, regardless of tachysystole, if nonreassuring fetal status occur (at the discretion by the 
provider), the oxytocin infusion will be turned off and restarted at ½ of the previous dose after 
30 minutes, as long as fetal heart tracing recovers. If fetal heart tracing does not recover, the 
general protocol on labor and delivery would generally warrant an expedited delivery via 
cesarean delivery. This decision will be made at the discretion of the provider. Therefore, 
cesarean delivery and operative vaginal delivery is reserved for the usual indications determined 
by the provider.  
Monitoring of maternal urine output is routinely done on labor and delivery every 4 hours. If 
oliguria occurs (<0.5cc/kg/hour), a basic metabolic panel will be obtained to assess for 
hyponatremia. If the sodium level is below 130 meq/L, the oxytocin infusion will be turned off 
until resumption of urine output or rise in sodium level to above 130meq/L.  
Patient will remain in nothing per oral status per routine guidelines on labor and delivery. Patient 
can receive other common obstetrical intervention per usual, including epidural placement for 
pain control, artificial rupture of membrane for labor progression, internal intrauterine pressure 
catheter or fetal scalp electrode placement for closer monitoring. Similarly, management of 2nd 
stage of labor after achieving full cervical dilation will be managed per routine care.  
Subsequently after delivery, a new bag of usual concentration of oxytocin will be used in all 4 
groups for postpartum oxytocin as per routine.  
When the maximum rate is reached at 20cc/hour, patient will be assessed by the provider for 
eligibility to continue to increase oxytocin dosage. This will also be done in the routine manner at 
the discretion of the provider. 
All woman/fetus pairs will be continuously monitored via Doppler/TOCO as per standard of care.  
Subject participation is expected to last until time of hospital discharge.  
Data collection 
Standard data points will be collected during the labor of each patient enrolled in the study: 
Demographic:  
Date of admission and discharge 
Age, race, parity, gravidity 
Weight, height and BMI 
Indication for induction 
Associating medical comorbidities 
Induction: 
 
Cervical exam and bishop score 
Start time for induction 
 
Tachysystole 
 
Terbutaline use 
 
Internal monitoring (intrauterine pressure catheter, fetal scalp electrode) 
 
Time of membrane rupture (spontaneous or artificial) 

 
 
 
 
 
 
 
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Time of onset of second stage labor 
 
Time of delivery of fetus, placenta 
 
Birth weight of fetus 
 
Apgar score of fetus at 1 and 5 minutes 
 
Type of delivery (vaginal, vacuum or forceps assisted, cesarean delivery) and indication 
 
If cesarean delivery, time when decision of cesarean delivery was made 
 
Total amount of oxytocin, median, mean, and maximum oxytocin rate 
 
Abnormal fetal heart tracing 
Maternal complications 
 
Postpartum hemorrhage 
 
Estimated blood loss 
 
Postpartum fever, chorioamnionitis, endomyometritis 
 
Pre-induction and Lowest postpartum hematocrit 
 
Uterine rupture 
 
Blood transfusion 
 
Incidence of oliguria 
Baby: 
 
Type of nursery admission (newborn or NICU) 
 
Umbilical cord gas if applicable 
No other PHI will be collected as part of this study. 
All the data above will be collected from the medical records and transcribed on a standardized data 
collection sheet and will be placed in a locked cabinet in the investigator’s office (please see 
attachment for data collection sheet). 
 
9) Cost to subjects  
 
There will be no additional costs to patients due to study procedures. Patients will be billed for their 
care per treatment received during their hospitalization per usual. Oxytocin is very inexpensive. Any 
increase in charge due to the high dose oxytocin protocol will be billed to the Department of 
OB/GYN. The department has awarded a small internal funding to cover the administrative and 
additional medication cost of this study.  
10) Risks to subjects 
Low dose oxytocin regimen is the current standard of care on labor and delivery in the United States. 
High dose oxytocin regimen is widely used internationally. Both regimens’ safety profile has been 
compared and validated in multiple meta-analysis including a Cochrane review as detailed above in 
the background section. Therefore, the American College of Obstetricians and Gynecologists had 
endorsed both regimens. It is important to emphasize that the following risks pertain to both the low 
dose (the current standard of care on L&D) and high dose protocol, and that the Cochrane review did 

 
 
 
 
 
 
 
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not find the high dose protocol to have additional risks to patients. Adverse events (AE) and serious 
adverse events (SAE) to oxytocin in mother includes: 
Cardiovascular: Cardiac arrhythmia, including premature ventricular contractions (SAE), 
subarachnoid hemorrhage (SAE), tachycardia (SAE), hypotension (SAE), hypertension (SAE) 
As discussed above, cardiovascular changes with high dose oxytocin were observed in studies in 
which patients received a large intravenous bolus over a short period (15-30 seconds). Secondary to 
these concerns, currently the standard of care is to administer oxytocin over a slow intravenous 
infusion 1,2. This study does not deviate from the standard of care protocol. Therefore, the 
investigator predicts a low cardiovascular risk to patients, risks that would be comparable with 
current standard of care. In addition, the investigator excluded mothers with previous serious 
cardiac disease to further decrease risks to subjects.  
Genitourinary: Uterine hypertonia (SAE), tachysystole (AE), uterine rupture (SAE), postpartum 
hemorrhage (SAE) 
These are well known side effects of oxytocin on the obstetrical floor and the absolute rates remain 
low. Again, as discussed above, these risks were evaluated and compared directly by multiple meta-
analysis and a Cochrane review. There was also no difference in serious maternal or neonatal 
morbidity or death between the high and low dose regimen. There was no difference in adverse 
outcomes, including maternal uterine rupture, postpartum hemorrhage, endometritis, estimated 
blood loss, abnormal fetal heart tracing, fetal Apgar, newborn resuscitation and neonatal intensive 
care unit admission 3-5. Therefore, the investigator believes that the risk to the patient will be similar 
to baseline.  
Tachysystole will be monitored continuously as a clinical parameter to direct patient care and 
protocol management as well as a secondary outcome variable. 
Endocrine and metabolic: Water intoxication (SAE), hyponatremia (SAE) 
Again, as described above, there were also old case reports originating from the 1970s about 
concerns over high dose oxytocin and its association with maternal hyponatremia or water 
intoxication 6,7. The hypothesis behind its association is due to the similarity between oxytocin and 
anti-diuretic hormone. These were largely single case reports in the setting of accidental large 
overdose of oxytocin in addition to large volume administration of electrolyte-free solutions. Since 
then, the practice of administering oxytocin is only given alongside isotonic lactated ringer or normal 
saline in a slow intravenous infusion fashion 8,9. This study does not deviate from the standard of 
care. Therefore, the investigator predicts a low risk to patients, risks that would be comparable with 
current standard of care. 
The following SAE and AE have been associated with oxytocin but frequency is not well defined and 
not well reported in the literature.  
Hematologic: pelvic hematoma (SAE), fatal afibrinogenemia (SAE) 
Misc: Anaphylactic reaction (SAE), nausea and vomiting (AE)  
 
Risks to fetus include: 
Due to induced uterine motility: bradycardia (SAE), premature ventricular contractions and other 
arrhythmias (SAE), permanent CNS or brain damage (SAE), fetal death (SAE), neonatal seizures (SAE)  

 
 
 
 
 
 
 
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Due to use of oxytocin in mother: low apgar scores (AE), neonatal jaundice (AE), neonatal retinal 
hemorrhage (SAE) 
 
Frequency of risks: 
The frequency of risks occurring for each risk is not well defined and not well reported in the 
literature. All above risks are considered to be rare, with the exception of:  
 
Tachysystole: This will be monitored continuously as a clinical parameter to direct patient care and 
protocol management, as written in the protocol. Also it is important to recognize that tachysystole 
occurs with the low dose protocol as well, which is the current standard of care. 
 
Nausea and vomiting: This is a common side effect of labor itself with or without oxytocin.  
 
It is important to recognize that these risks exist equally in the low dose protocol, which is the 
current standard of care on Labor and Delivery. When a patient presents for an induction of labor 
with oxytocin, they are subjected to all of the above risks, regardless of whether they are enrolled as 
a study participant. The only way to avoid these risks completely, is for a patient to not receive 
oxytocin (which is required if patient agreed to undergo an induction of labor). These risks above 
have been well monitored throughout clinical practice since the 1970s, and large Cochrane review as 
detailed above had provided good safety profile for this drug in both the low and high dose regimen. 
All serious adverse events (SAE) will be monitored and documented closely during the study, and will 
result in discontinuation of the study protocol immediately. The management of AE is detailed in the 
protocol. If more than 20% of patients enrolled in the study have an AE/SAE, enrollment in the study 
will be stopped pending an evaluation of the frequency of AE/SAE.  
1. Svanstrom MC, Biber B, Hanes M, Johansson G, Naslund U, Balfors EM. Signs of myocardial ischemia after injection 
of oxytocin: a randomized double-blinded comparsion of oxytocin and methylergometrine during cesarean section. 
British Journal of Anaesthesia 100 (5): 683-9 (2008). 
2. Bhattacharya S, Ghosh S, Ray D, Mallik S, Laha A. Oxytocin administration during cesarean delivery: randomized 
controlled trial to compare intravenous bolus with intravenous infusion regimen. J Anaesthesiol Clin Pharmacol. 
2013 Jan-Mar; 29(1): 32-35. 
3. Wei SQ, Luo ZC, Qi HP, Xu H, Fraser WD. High dose vs. low dose oxytocin for labor augmentation: a systematic 
review. Am J Obstet Gynecol 2010 Oct; 203(4): 296-304.  
4. Zhang J, Branch DW, Ramirez MM, Laughon SK, Reddy U, Hoffman M, Bailit J, Kominiarek M, Chen Z, Hibbard JU. 
Oxytocin regimen for labor augmentation, labor progression, perinatal outcomes. Obstet Gynecol 2011 Aug; 118 (2 
Pt 1):249-56. 
5. Budden A, Chen LJY, Henry A. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term. 
Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD009701.  
6. Jensen I, Bruns BJ. Water intoxication after oxytocin-induced midtrimester abortion. NZ Med J. 1979 April 25; 
89(634):300-2. 
7. Lauersen NH, Birnbaum SJ. Water intoxication associated with oxytocin administration during saline-induced 
abortion. Am J Obstet Gynecol. 1975 Jan 1; 121(1): 2-6. 
8. Higgins J, Gleeson R, Holohan M, Coone C, Darling M. Maternal and neonatal hyponatremia: a comparison of 
Hartmanns solution with 5% dextrose for the delivery of oxytocin in labor. European Journal of Obstetrics and 
Gynecology and Reproductive Biology 68 (1996) 47-48. 

 
 
 
 
 
 
 
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9. Moen V, Burdin L, Rundgren M, Irestedt L. Hyponatremia complicating labor – rare or unrecognized? A prospective 
observational study. BJOG 2009; 116: 552-561. 
11) Potential benefits to subjects and/or society 
Study patients in the high dose oxytocin groups may experience a faster labor course or lower 
cesarean delivery rate if our hypothesis is correct. 
Benefits to society at large include potential systematic changes to management of obese pregnant 
women in labor. High dose oxytocin regimen may improve pregnancy outcome with faster labor 
course without an increase in morbidity, and may affect a change in cesarean delivery rate. 
 
12) Provisions to protect the privacy of subjects and the confidentiality of data 
a. Protection of subject privacy: Privacy of subjects will be respected always during the study. 
Patients will only be consented in a private area. Patients are asked during all encounters 
with a physician whether they would like their family or friends present. 
b. Protection of data confidentiality:  
A data collection sheet will be used to record data. This data will then be stored in a coded 
fashion with key code assigned, in a computer excel spreadsheet on the principal 
investigator’s computer, located in room 8327G in the Department of Obstetrics and 
Gynecology. Only the PI will have access to the key code. Because every account on the 
computer is password protected, the only person who has access to this computer is the PI 
herself. Only personnel on the VOTF will be granted access to this data/spreadsheet. The data 
collection sheet and the patient consent forms will be kept in the same room in a locked file 
cabinet. These data collection sheets, the patient consent documents as well as the key code 
will be stored for a period of 6 years after conclusion of study and destroyed thereafter. 
13) Access to Private Information 
a. Access to medical records (HIPAA): Patients agreeing to participate in this study will be made 
aware that record review of their, and their child’s, protected health information will occur as 
a part of the study. The consent form includes HIPAA consent. Only investigators on the VOTF 
can access their PHI, as described above. A list of data to be collected is detailed above. 
14) Subject compensation 
There will be no monetary compensation provided to the subjects for participating in this study. 
15) Medical care and compensation for injury  
There are no expected maternal or fetal injuries attributed to the high dose oxytocin regimen 
compared to the low dose oxytocin regimen as discussed above. In the unforeseeable event that a 
complication occurs, the patient will be billed for their medical care as they would with any other 
induction of labor. 
16) Monitoring for subject safety  
The study protocol has built in monitoring measures for specific clinical scenarios in the setting of 
adverse reactions. These include specific detailed protocols for tachysystole, nonreassuring fetal 
status as well as oliguria. 

 
 
 
 
 
 
 
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For every 10 enrollments, data will be monitored by the principal investigator and reviewed by an 
independent reviewer within the department of ob/gyn. This personnel will have a background in 
ob/gyn and will be assigned by the principal investigator. Data will be reviewed in a blinded fashion 
to prevent introducing bias into the study. In addition, all serious adverse events (SAE) will be 
monitored and documented closely during the study with each enrollment, and will result in 
discontinuation of the study protocol immediately. The management of AE is detailed in the 
protocol. If more than 20% of patient enrolled in the study have an AE/SAE, enrollment in the study 
will be stopped pending an evaluation of the frequency of AE/SAE. This will be reported to the IRB. 
The principal investigator and the research staffs will monitor protocol adherence closely with each 
enrolled participant. Any protocol deviation will be reported to the IRB as required.  
17) Withdrawal of subjects 
A patient may withdraw from this research at any time. The infusion of the study drug can be 
stopped at any time. A patient may withdraw for any reason, including a desire to stop induction of 
labor and undergo an elective cesarean delivery. Subjects will not be at increased risk when they are 
abruptly withdrawn from the study because of the short half-life of oxytocin (4.5 minutes). Data 
collection on patients who have completed more than 30 minutes of study drug will be kept and 
included in the data analysis (intention to treat analysis). Any withdrawal secondary to side effects or 
adverse effects will be recorded and monitored. Only verbal withdrawal is required. 
18) Sharing of results with subjects  
The results of the study will not be shared with the subjects, families or the institution. Patients will 
not be contacted in the future in relation to the results of the research. The intention is to publish 
the results of this research and patients will have access to the information gained through this 
forum.  
There will be no additional charges billed to the insurance for any procedures associated with this 
study. 
19) Future use and long-term storage of data or specimens 
Data will not be kept for future research. 
20) Clinical Trials.gov Information 
 ClinicalTrials.gov "NCT" number for this trial (provide):  
 Registration pending 
 
Clinical trial does not require registration (explain):  
 
SECTION 4: LIST OF ATTACHMENTS FOR THIS SUBMISSION (REQUIRED) (Items listed here are 
expected to be attached as separate documents. These documents will appear in the UA HSPP IRB 
approval letter as 'documents submitted concurrently' with the review.) 
Document Name 
Version Date 
1. F107/VOTF 
1. 02/27/17 
2. Appendix A/Children 
2. 02/27/17 
3. Appendix B/Drugs/devices 
3. 02/27/17 
4. Appendix D/pregnant women and neonate 
4. 01/31/17 

 
 
 
 
 
 
 
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5. Drug information 
5. 01/31/17 
6. Appendix F/waiver of consent 
6. 02/27/17 
7. T503a/consents 
7. 03/31/17 
8. Data collection form 
8. 01/31/17 
9. Biosketch of PI (Meghan Hill) and Co PI (Ruth Wei) 
9. 02/27/17 
10. Protocol 
10. 03/31/17 
11. autographs 
11. 01/31/17 
See HSPP website for submission requirements. 
Items needed for approval: 
• 
Word Versions of Application, Consents, Recruitment and Data Collection  
• 
F107: Verification of Training Form 
• 
Current PI/Co-PI CVs or biosketch, if not included with copy of grant application 
• 
Informed Consent/Permission/Assent Form(s) – including study specific release of information documents, DHHS 
approved sample consent forms.  If consent will not be documented in writing, a script of information to be provided 
orally to subjects 
 
Other Items as applicable: 
• 
Appendix A - Children 
• 
Appendix B - Drug/Device 
• 
Appendix C- Multi Site Research 
• 
Appendix D- Pregnant Women and Neonates 
• 
Appendix E- Prisoners 
• 
Appendix F- Waiver of Consent/ PHI 
• 
Appendix G- Exception from Informed Consent (EFIC) 
• 
Appendix H- Native American 
• 
Biosafety Review letter (for UA - Institutional Biosafety Committee) 
• 
Certificate of Confidentiality 
• 
Compressed Gases Review letter (for UA – Research Instrumentation) 
• 
Contract – complete or draft copy of contract including budget 
• 
Data Collection Tools – surveys, questionnaires, diaries not included in the protocol, data abstraction form for 
records review 
• 
Data Monitoring Charter and Plan  
• 
Drug/Device information – Investigator's Brochure, drug product sheet, device manual, user's manual, instructions 
for use, package insert, IND/IDE documentation, FDA 1572 form, 510k indication, FDA exemption, sponsor 
determination of device risk, etc. 
• 
Export Control Review 
• 
Grant Application(s) – cover-to-cover copy of grant, regardless of home institution or funding agency, and a copy of 
the Notice of Grant Award.   
• 
Multi-site information (for sites engaged in research where the UA is the IRB of record)  
o 
Copy of any approvals granted from that site (including determinations if this site has an IRB of its own) 
o 
Site-specific F107 
o 
Copy of the site's human subjects training policy 
o 
CV and medical license (if applicable) of site PI 
• 
Other Approval letters (e.g., school districts, Tribal, other IRB approvals) 
• 
Participant Materials – written materials to be provided to or meant to be seen or heard by subjects (e.g. study 
newsletter, physician to participant letter, wallet cards, incentive items, holiday/birthday cards, certificates, 
instructional videos/written guides, calendars, certification of achievement, etc.) 
• 
Payer coverage analysis 

 
 
 
 
 
 
 
Page 23 of 23 
 
HSPP Use Only: 
Form 200 v 2016-07 
• 
PHI Authorization Form(s) 
• 
Protocol – including all amendments/revisions, sub- or extension-studies 
• 
Radiation Safety Review letter- needed regardless if the radiation device is approved and used standard of care 
• 
Recruitment Materials – telephone scripts, flyers, brochures, websites, email texts, radio/television spots, 
newspaper advertisements, press releases, etc. 
• 
Scientific Review Committee letter (for cancer related projects – AZCC SRC; other units as applicable if the unit has a 
scientific review committee) 
• 
Site Authorizations for research purposes and/or access to administrative records/samples 
o 
External sites (such as schools, other hospitals or campuses, etc.) 
o 
UAHS Research Portal feasibility review approval 
• 
Travel Authorization documentation (for UA – Office of Global Initiatives) 
• 
Use of retrospective research samples and/or data – IRB approval letter, original consent under which 
samples/data were collected, letter allowing access to samples