POM PROM: Pitocin or Oral Misoprostol for PROM IOL in Nulliparous Women With Unfavorable Cervical Exams
Phase: PHASE4
Conditions: PROM
Sponsor: University of Pennsylvania

Pitocin or Oral Misoprostol for PROM IOL in Nulliparous Women with Unfavorable Cervical 
Exams 
NCT04028765 
 
Protocol Version 3 
Uploaded March 5, 2024 
Last updated January 27, 2020 
 
 

 
 
Study Summary 
Title 
Pitocin or Oral Misoprostol for PROM IOL in 
Nulliparous Women with Unfavorable Cervical 
Exams 
Short Title 
POM PROM  
Methodology 
Randomized trial 
Study duration 
24 Months 
Study Center (s) 
Single-center 
Objective 
To determine if Pitocin (oxytocin) or oral 
misoprostol results in a shorter interval to 
delivery after the start of induction in nulliparous 
women with unfavorable cervical exams with  
premature rupture of membranes (PROM). 
Number of Subjects 
155 
Diagnosis and Main Inclusion Criteria 
PROM > 36 weeks gestation; Singleton gestation 
in vertex presentation; Cervix < 2 cm dilated and 
Bishop < 8; No contraindication to vaginal 
delivery; No evidence of infection 
Study Product (s), Dose, Route, Regimen 
Oral Misoprostol – 50 mcg q4H 
IV Pitocin (Oxytocin) – 2 mU/min, increased by 2 
mU/min to achieve 4-5 contractions in 10 
minutes with cervical change. Max dose 40 
mU/min 
Duration of administration 
Oral Misoprostol – Max 6 doses or until cervical 
ripening and/or delivery has been achieved 
Pitocin – Until delivery 
Primary Outcome 
Time from IOL to delivery (hours) 
Statistical methodology 
Intention to treat analysis, chi-square test for 
categorical variables, two-sample t-test for 
continuous variables 
 
1 BACKGROUND AND RATIONALE 
1.1 Condition Background 
Premature rupture of membranes (PROM) occurs in approximately 8% of pregnancies at term.1 
Although onset of spontaneous labor is often prompt after membrane rupture, a delay from 
PROM to labor is associated with an increased risk of intrauterine infection and its associated 
maternal and fetal complications. For this reason, ACOG endorses induction of labor for PROM 
“if spontaneous labor does not occur near the time of presentation.”1 

1.2 Rationale 
The optimal method for PROM induction is less clear. Prior literature has examined the use of 
Pitocin (Oxytocin), vaginal and oral misoprostol, and dinoprost with mixed results. The 
TermPROM study found an increased risk of chorioamnionitis and NICU admission among 
women treated with vaginal misoprostol for induction.2  
The postulated link between vaginal misoprostol and chorioamnionitis is the need for vaginal 
examination for placement of the misoprostol; more vaginal examinations could potentially 
increase the risk for infection. Utilizing oral misoprostol would eliminate the need for a vaginal 
exam for administration, thereby potentially mitigating this risk of infection. Currently, vaginal 
and oral misoprostol as well as Pitocin (Oxytocin) are used routinely in clinical care based on 
provider discretion.  
 
Among 7 randomized controlled trials examining the use of oral misoprostol as compared to 
Pitocin (Oxytocin), two found oral misoprostol to result in faster induction to delivery, two 
found Pitocin to result in faster deliveries, and the remaining two found no difference between 
the two.3-8 These studies are limited by small sample size, inadequate reporting of patient 
demographics, varied misoprostol and Pitocin (Oxytocin) protocols, and inconsistent primary 
outcomes. Therefore, the utility of oral misoprostol in this population has not been established. 
Furthermore, its efficacy in specific patient populations is unreported in the literature. 
 
2 
STUDY AIMS 
2.1 AIM 1:  
To determine if Pitocin (Oxytocin) or oral misoprostol results in a shorter interval to delivery 
after the start of induction among nulliparous women with unfavorable cervical exams with 
PROM. 
 
2.2 Endpoints 
2.2.1 
Primary Endpoint 
• 
Time (hours) from start of IOL to delivery 
2.2.2 
Secondary Endpoints 
• 
Suspected intraamniotic infection (Defined as maternal fever plus 1 or 
more of maternal leukocytosis, purulent cervical drainage, or fetal 
tachycardia 
• 
Time (hours) from PROM to delivery 
• 
Time (hours) from IOL to vaginal delivery 
• 
Time (hours) from PROM to vaginal delivery 
• 
Cesarean delivery 
• 
Composite maternal outcome 

o Postpartum hemorrhage, blood transfusion, endometritis, 
wound infection, VTE, hysterectomy, ICU admission, 
readmission within 4 weeks, death 
• 
Composite neonatal outcome 
o ICN adm > 48 hours, neonatal blood transfusion, HIE, IVH grade 
3 or 4, headcooling, severe RDS, NEC, Sepsis, Death 
• 
Patient satisfaction – as measured by Birth Satisfaction Scale- Revised 
(BSS-R) 
3 
PATIENT ELIGIBILTY 
Subjects must meet all of the inclusion and exclusion criteria to be enrolled to the study. Study 
treatment may not begin until a subject is consented and randomized. 
3.1 Inclusion Criteria 
English-speaking 
≥ 18 years of age 
PROM ≤24 hours with no evidence of labor 
PROM – Standard clinical diagnosis 
Labor – >3 painful contractions in a 10 minute period, averaged over 30 minutes 
> 36 weeks gestation 
Agreeable to induction of labor 
Singleton pregnancy 
Vertex presentation 
Cervical dilation < 2 cm and Bishop score < 8 
Exam done by senior resident, fellow, midwife or attending to confirm eligibility 
3.2 Exclusion Criteria 
Contraindication to misoprostol (Prior Cesarean section, prior uterine surgery) 
Other contraindication to vaginal delivery 
Intrauterine fetal demise 
Major congenital anomaly 
Chorioamnionitis at time of admission 
36w-36w6d with unknown Group B Strep (GBS) status 
3.3 Vulnerable patient populations 
Pregnant women are considered a vulnerable population. As the condition of interest is a 

pregnancy-related and specific condition, it is unavoidable to exclude pregnant women from 
this research study. Oral misoprostol and Pitocin (Oxytocin) however, are currently used in 
clinical practice so the risks to this population are minimally increased from that experienced in 
routine clinical care. 
 
Furthermore, neonates are considered a vulnerable population. We will be collecting data on 
neonates for our composite neonatal outcome. All risks to this vulnerable population will be 
less than minimal risk as it will involve chart review only after delivery. Subjects will be made 
aware that we will be collecting information on their neonates within the consent form. 
 
3.4 Ensuring Necessary Medical Interventions 
Enrollment in this study will alter the induction agent utilized after diagnosis of PROM. 
Continuous EFM and tocometry will occur on all patients in labor, consistent with standard of 
care. Mechanical cervical ripening will not be performed. The remainder of clinical care in 
labor will be at the covering OB providers’ discretion. The frequency and timing of cervical 
examinations will occur per provider discretion. Standard treatment for GBS positive and 
GBS unknown patients will occur. The use of internal fetal monitoring and intrauterine 
pressure catheter will be at the discretion of the OB provider. Standard obstetric indications 
for cesarean delivery will be also be at the discretion of the OB provider. 
 
3.5 Potential Benefit to Participants 
Participation in this study is for research purposes and there is no direct health benefit to the 
subjects.  
 
4 
TREATMENT ARMS 
4.1 Treatment Dosage and Administration 
§ 
Oral Misoprostol 50 mcg q4H for up to 6 doses 
o 
Transition to Pitocin (Oxytocin) as determined by primary OB 
provider after cervical ripening is no longer indicated 
§ 
Pitocin (Oxytocin) – The standard hospital protocol will be utilized. This regimen 
starts at a dose of 2 mU/min IV.  
o 
The dose is increased by 2 mU every 15 minutes until 
contractions q2-3 minutes apart resulting in cervical change.  
o 
The max dose is 40 mU/min. 
4.2 Toxicities  
• 
There are no known toxicities with the doses of misoprostol and 
Pitocin(Oxytocin) that we are using. One known possible side effect of oral 
misoprostol is GI distress (nausea, vomiting, diarrhea). If this occurs, attempts 
will be made to treat these symptoms with antiemetics or antidiarrheals as 
needed. If unresponsive to treatment, the medication will be discontinued. All 
women receiving misoprostol will also be monitored for frequency of contractions. 
The medication will not be administered if contractions >3 per 10 minute period, 
averaged over a 30 minute period. 
• 
All women receiving Pitocin (Oxytocin) will also be monitored for frequency of 
contractions. The dose will be titrated to prevent tachysystole and fetal distress 
as per current Hospital of UPenn protocol. If tachysystole or fetal distress 
develop, the medication will be discontinued and the condition managed per OB 
provider discretion. Medication can be restarted upon resolution of tachysystole 
or confirmation of fetal well-being. 

4.3 Concomitant Medications/Treatments 
• 
No additional induction agents will be utilized in conjunction with misoprostol or 
Pitocin (Oxytocin). 
4.4 Duration of Therapy 
• 
Oral misoprostol can be continued until max dose has been reached or the 
primary OB provider has deemed cervical ripening is no longer indicated 
• 
Pitocin (Oxytocin) can be continued throughout the course of labor as per current 
HUP guidelines. 
4.5 Duration of Follow Up 
Women/neonate dyads will be followed for the development of any maternal or neonatal 
complications through the duration of the postpartum hospital stay as well as for 
readmissions within four weeks of delivery. 
4.6 Blinding 
Due to the nature of the treatment arms, neither providers nor participants will be blinded to 
their treatment arm.  
 
5 
STUDY PROCEDURES 
5.1 Screening for Recruitment and Recruitment Process 
Women meeting the criteria listed in section 3.1 will be invited to participate in the study and 
written informed consent will be obtained from those who choose to participate.  
 
5.2 Randomization 
Eligible, consented women will be randomized via a random generated randomization 
scheme within RedCap. The randomization scheme will be generated by a statistical 
associate not involved in the study. 
 
5.3 Procedures During Treatment 
After randomization, the appropriate medication will be ordered in Epic by the covering 
clinician and obtained through inpatient pharmacy as is the current clinical practice. The 
resulting trial arm will be disclosed to the patient and the patient RN.  
• 
For participants randomized to oral misoprostol, the RN will administer and 
record the time of first dose. Re-dosing of medication will occur per the schedule 
described in sections 4.1  
• 
For participants randomized to Pitocin (Oxytocin), the RN will begin Pitocin 
(Oxytocin) infusion and record the time of infusion start. Dose adjustments will be 
made according to the clinical protocol described in section 4.1. 
The remainder of clinical care in labor and delivery will occur as per primary OB provider’s 
discretion as described in section 3.4. 
5.4 Follow-up Procedures 
During the postpartum hospital stay, women will be approached to complete a validated 
patient satisfaction survey, the BSS-R.  
 
 
5.5 Protections Against Physical Risk 
There is minimal risk to the use of oral misoprostol or Pitocin(oxytocin) during labor. Both of 
these medications are currently employed in clinical use at the Hospital of the University of 

Pennsylvania. A DSMB comprised of individuals who are not investigators on the trial will be 
utilized to monitor for adverse outcomes. A list of mandatory events that should be reported 
to the DSMB within 24 hours of occurrence will be supplied to all clinicians and research 
coordinators managing trial patients. Also all serious adverse events will be recorded and 
reported to the institutional review board. 
 
5.6 Protection against Loss of Privacy/Breech of Confidentiality 
In order to protect a potential subject’s privacy, study staff will only approach potential 
subjects in a private setting. Once consented, we will take multiple steps to protect the study 
subject from breach of confidentiality. The list linking the subject’s name and medical record 
number will be kept behind the hospital firewall in a password-protected file. This file is only 
accessible through the hospital server to those individuals given password approval to 
access the file. Furthermore, the electronic database (REDCap) will be coded with a unique 
study identifier rather than with any individually identifiable private information. No PHI will be 
shared with anyone outside the institution.  
 
6 
ADVERSE EVENTS 
6.1 Adverse Event Monitoring 
Adverse event data collection and reporting will be done to ensure the safety of subjects 
who will enroll be enrolled in thus study. Adverse events will be reported in a routine 
manner at scheduled times during the trial. Additionally, certain adverse events will be 
reported in an expedited manner to allow for optimal monitoring of patient safety and care.  
 
All patients experiencing an adverse event, regardless of its relationship to study 
drug/device, will be monitored until:  
Ø the adverse event resolves or the symptoms or signs that constitute the adverse 
event return to baseline;  
Ø any abnormal laboratory values have returned to baseline;  
Ø there is a satisfactory explanation other than the study drug for the changes 
observed; or 
Ø death. 
6.2 Definitions 
6.2.1 
Definition of Adverse Event 
An adverse event (AE) is any untoward medical occurrence in a patient receiving 
study treatment and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an experimental intervention, whether or not related to 
the intervention.  
6.2.2 Severity of Adverse Events 
The severity of an AE is graded as follows: 
Mild (grade 1): the event causes discomfort without disruption of normal daily 
activities. 

Moderate (grade 2): the event causes discomfort that affects normal daily 
activities. 
Severe (grade 3): the event makes the patient unable to perform normal daily 
activities or significantly affects his/her clinical status. 
Life-threatening (grade 4): the patient was at risk of death at the time of the 
event. 
Fatal (grade 5): the event caused death. 
6.2.3 Serious Adverse Events 
A “serious” adverse event is defined in regulatory terminology as any untoward 
medical occurrence that: 
Results in death. 
If death results from (progression of) the disease, the disease should 
be reported as event (SAE) itself. 
Is life-threatening (i.e. the patient was at risk of death at the time of the event). 
Requires in-patient hospitalization or prolongation of existing hospitalization for ≥ 
24 hours. 
Results in persistent or significant disability or incapacity. 
Is an important medical event. Essentially, any event that does not meet the 
above criteria, but that in the judgment of the investigator jeopardizes the patient, 
may be considered for reporting as a serious adverse event.  
 
 
 
For the purposes of this study, the adverse events that would meet any of these 
criteria are: maternal death, ICU admission, anaphylaxis, hysterectomy will be 
documented and reported as a SAE. In addition, any unexpected event which the 
PI believes to have been cause or contributed to by the intervention, regardless 
of whether it resulted in hospitalization, will also be considered an AE or SAE.   
6.3 Steps to Determine If an Adverse Event Requires Expedited Reporting 
Step 1: Identify the type of adverse event   
 
Step 2: Grade the adverse event  
 
Step 3: Determine whether the adverse event is related to the protocol therapy  
Attribution categories are as follows: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 

- Unrelated – The AE is clearly NOT related to the study treatment. 
 
Step 4:  
Determine the prior experience of the adverse event.  
Expected events are those that have been previously identified as resulting from 
administration of the agent. An adverse event is considered unexpected, for expedited 
reporting purposes only, when either the type of event or the severity of the event is not 
listed in: 
• 
the current known adverse events listed in the Agent Information Section of this 
protocol; 
• 
the drug package insert; 
• 
the current Investigator’s Brochure 
6.4 Reporting Requirements for Adverse Events 
6.4.1 
Expedited Reporting 
• 
The Principal Investigator will be notified within 24 hours of learning of any 
serious adverse events, regardless of attribution, occurring during the study 
or within 30 days of the last administration of the study drug.  
• 
The University of Pennsylvania IRB must be notified within 10 business 
days of “any unanticipated problems involving risk to subjects or others” 
(UPR/UPIRSO). 
The following events meet the definition of UPR: 
1. Any serious event (injuries, side effects, deaths or other problems), which 
in the opinion of the Principal Investigator was unanticipated, involved 
risk to subjects or others, and was possibly related to the research 
procedures. 
2. Any serious accidental or unintentional change to the IRB-approved 
protocol that alters the level of risk. 
3. Any deviation from the protocol taken without prior IRB review to 
eliminate apparent immediate hazard to a research subject. 
4. Any new information (e.g., publication, safety monitoring report, updated 
sponsor safety report), interim result or other finding that indicates an 
unexpected change to the risk/benefit ratio for the research. 
5. Any breach in confidentiality that may involve risk to the subject or others. 
6. Any complaint of a subject that indicates an unanticipated risk or that 
cannot be resolved by the Principal Investigator. 
6.4.2 
Routine Reporting 
All other adverse events- such as those that are expected, or are unlikely or definitely not 
related to the study participation- are to be reported annually as part of regular data 
submission. 
6.5 Stopping Rules  
This study does not have a primary safety endpoint or place study subjects at high risk.  
7 
STUDY DESIGN/STUDY ENDPOINTS 

This will be a prospective, randomized, single center study on the efficacy of Pitocin(oxytocin) versus 
oral misoprostol for PROM induction in nulliparous women with unfavorable cervical examinations. 
Please refer to section 2.3 for endpoints.  
7.1 Sample Size and Accrual 
The sample size is based on the mean time to delivery with Pitocin(oxytocin) after PROM IOL 
of 10.4 hours, with a standard deviation of 4.3 hours. For a power of 80% and an alpha of 
0.05, 148 women would be needed to find a 2-hour difference in time to delivery. To account 
for drop out, we plan to enroll 155 women.  
 
We estimate 15-20 eligible women deliver at HUP per month. We anticipate approaching 
80% of these women or approximately 14 per month. With an estimated 50% consent rate, 
we would enroll approximately 7 women per month. Therefore, we would need 24 months to 
reach our target enrollment of 155 women.  
 
7.2 Data Analyses Plans 
Measures of relative risk will include 95% confidence intervals. Descriptive statistics will be 
presented as mean with standard deviation, median with interquartile range, or proportion with 
95% confidence interval based on data type and distribution.  Comparisons between groups 
will be performed using a Chi-square or Fisher’s exact test for categorical variables and 
parametric or non-parametric tests for continuous variables, as appropriate. Intention-to-treat 
analyses will be conducted such that all patients with available follow-up measures will be 
included in the analysis. Statistical analyses were conducted in STATA, version 12.0 (College 
Station, Texas). Two-tailed P values of <0.05 will be considered statistically significant. 
8 
STUDY MANAGEMENT 
8.1 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, 
or financial gain greater than the minimum allowable by their institution, etc.) must have 
the conflict reviewed by the PI and the IRB.  All investigators will follow the University’s 
conflict of interest policy. 
8.2 Collection of data 
We will record data on each patient regarding their demographics, obstetrical and medical 
history, labor and delivery admission through postpartum discharge. We will also collect 
neonatal outcomes on their infants through hospital discharge. 
8.2.1 
Private information 
Only the study staff listed on the protocol approved by the Institutional Review Board will 
have access to individually identifiable private information about human subjects. The only 
individually identifiable private information about human subjects that will be collected for 
research purposes is the subject’s name and medical record number for the purpose of 
linking the subject to their unique study identifier. 
8.2.2 
Data Protection 
The individually identifiable private information that will be collected is name and medical 
record number for the purposes on linking the subject to their unique study number for 
chart review. The file linking the study number to the name, medical record number and 
phone number will be kept in a password-protected file on a secure server. Data will be 

collected primarily by the research team. The electronic database (REDCap) will be stored 
behind the institution’s firewall in a password-protected file. 
8.3 Institutional Review Board (IRB) Approval and Consent  
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations. The IRB should approve the consent form and 
protocol. 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to Good Clinical Practice (GCP) 
and to ethical principles that have their origin in the Declaration of Helsinki. 
Before recruitment and enrollment onto this study, the patient will be given a full 
explanation of the study and will be given the opportunity to review the consent form. Each 
consent form must include all the relevant elements currently required by the FDA 
Regulations and local or state regulations. Once this essential information has been 
provided to the patient and the investigator is assured that the patient understands the 
implications of participating in the study, the patient will be asked to give consent to 
participate in the study by signing an IRB-approved consent form. 
Prior to a patient’s participation in the trial, the written informed consent form should be 
signed and personally dated by the patient and by the person who conducted the informed 
consent discussion. 
8.4 
Data Management and Monitoring/Auditing 
8.4.1 
Data Safety and Monitoring Plan 
Safety monitoring will be performed periodically by the principal investigator. This will 
include assessment of accuracy of data recording, assuring de-identification of data, and 
that there is appropriate locked storage of data material. There will be no planned interim 
analyses. An advisory board will be created for continual oversight of the project. It will be 
comprised of faculty members within the department with extensive experience in 
prospective clinical trials. They will perform periodic reviews of safety data from this 
study. The DSMB that will be created is attached.  
8.5 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, and 
well-being of the study patient requires alternative treatment, the study shall be 
conducted exactly as described in the approved protocol.  
8.5.1 
Emergency Modifications 
Investigators may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to trial subjects without prior IRB approval.  
For any such emergency modification implemented, a IRB modification form must 
be completed within five (5) business days of making the change.  

8.5.2 
Other Protocol Deviations/Violations 
All other planned deviations from the protocol must have prior approval by the 
Principal Investigator and the IRB. According to the IRB, a protocol deviation is 
any unplanned variance from an IRB approved protocol that:  
• 
Is generally noted or recognized after it occurs 
• 
Has no substantive effect on the risks to research participants 
• 
Has no substantive effect on the scientific integrity of the research plan or the 
value of the data collected  
• 
Did not result from willful or knowing misconduct on the part of the 
investigator(s).  
 
An unplanned protocol variance is considered a violation if the variance: 
• 
Has harmed or increased the risk of harm to one or more research participants. 
• 
Has damaged the scientific integrity of the data collected for the study. 
• 
Results from willful or knowing misconduct on the part of the investigator(s). 
• 
Demonstrates serious or continuing noncompliance with federal regulations, 
State laws, or University policies. 
 
If a deviation or violation occurs without prior approval from the Principal 
Investigator, the ensuing guidelines will be followed: 
 
Protocol Deviations: Personnel will report to any sponsor or data and safety 
monitoring committee in accordance with their policies. Deviations should be 
summarized and reported to the IRB at the time of continuing review. 
 
Protocol Violations: Study personnel should report violations within one (1) week 
of the investigator becoming aware of the event using the same IRB online 
mechanism used to report Unanticipated Problems.  
8.6 Record Retention 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, monitoring logs/letters, and regulatory documents (e.g., protocol and 
amendments, IRB correspondence and approval, signed patient consent forms). 
Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical 
research study. 
Government agency regulations and directives require that the study investigator must 
retain all study documentation pertaining to the conduct of a clinical trial. In all other cases, 
study documents should be kept on file until three years after the completion and final study 
report of this investigational study. 

8.7 Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment 
of all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol 
and all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during and 
after study completion. 
 
The Principal Investigator will be responsible for assuring that all the required data will be 
collected and entered onto the Case Report Forms. Periodically, monitoring visits will be 
conducted and the Principal Investigator will provide access to his/her original records to 
permit verification of proper entry of data. At the completion of the study, all case report 
forms will be reviewed by the Principal Investigator and will require his/her final signature 
to verify the accuracy of the data. 
9 
References  
1Prelabor rupture of membranes. ACOG Practice Bulletin No 188. 2018. 
2Hannah ME, Ohlsson A, Farine D eta al. Induction of labor compared with expectant management for prelabor rupture of 
membranes at term. TERMPROM Study Group. New England Journal of Medicine. 1996; 334(16): 1005-1010.  
3Al-Hussaini TK, Abdel-Aal SA, Youssef MAM. Oral Misoprostol v. intravenous oxytocin for labor induction in women with prelabor 
rupture of membranes at term. International Journal of Gynecology and Obstetrics. 2003; 82(1): 73-75.  
4Mozurkewich E, Horrocks J, Daley S et al. The MisoPROM study: A multicenter randomized comparison of oral misoprostol and 
oxytocin form premature rupture of membranes at term. American Journal of Obstetrics and Gynecology. 2003; 4(189): 
1026-1030 
5Crane J, Delaney T, Hutchens D. Oral misoprostol from premature rupture of membranes at term. American Journal of Obstetrics 
and Gynecology. 2003; 3(189): 720-724. 
6Ngai S, Chan Y, Lam S, Lao T. Labour characteristics and uterine activity: misoprostol compared with oxytocin in women at term with 
prelabour rupture of membranes. BJOG. 2000; 2(107): 222-227. 
7Butt K, Bennett K, Crane J, Hutchens D, Young D. Randomized comparison of oral misoprostol and oxytocin for labor induction in 
term prelabor membrane rupture. Obstetrics and Gynecology. 1999; 94(6): 994-999. 
8Mbaluka CM, Kamau K, Karanja JG, Mugo N. Effectiveness and safety of 2-hourly 20 mcg oral misoprostol solution compared to 
standard IV oxytocin in labour induction due to prelabor rupture of membranes at term: a randomized clinical trial at 
Kenyatta National Hospital. East African Medical Journal. 2014;91(9): 303-310.