PROM
Conditions
Brief summary
Premature rupture of membranes (PROM) is a common occurrence of pregnancies at term. A delay from PROM to labor is associated with an increased risk of intrauterine infection and associated maternal and fetal morbidity; therefore, induction of labor (IOL) is recommended. The ideal agent for IOL is not known, particularly among specific subpopulations. The primary aim of this study is to determine if oxytocin (Pitocin) or oral misoprostol results in a shorter interval to delivery after the start of induction among nulliparous women with unfavorable cervical exams with term PROM.
Detailed description
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, the American College of Obstetricians and Gynecologists (ACOG) endorses induction of labor for PROM if spontaneous labor does not occur near the time of presentation. 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 Neonatal Intensive Care Unit (NICU) admission among women treated with vaginal misoprostol for induction. 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 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 oxytocin, two found oral misoprostol to result in faster induction to delivery, two found oxytocin to result in faster deliveries, and the remaining three found no difference between the two.3-9 These studies are limited by small sample size, inadequate reporting of patient demographics, varied misoprostol and 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. The primary aim of this study is to determine if 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.
Interventions
DRUGMisoprostol
Oral misoprostol 50 mcg every 4 hours for up to 6 doses or until cervical ripening is no longer indicated
DRUGOxytocin
IV Oxytocin 2 milliunits (mU)/min, increased by 2mU/min q15 minutes per hospital protocol
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* English Speaking * PROM \</= 24 hours with no evidence of labor * \>/= 36 weeks gestation * Agreeable to induction of labor * Nulliparous * Singleton pregnancy * Vertex presentation * Cervical dilation \</=2 cm AND Bishop score \< 8
Exclusion criteria
* Prior cesarean section * Other contraindication to vaginal delivery * Intrauterine Fetal Demise * Major Congenital Anomaly * Intraamniotic infection diagnosed at time of admission * 36 weeks - 36 weeks and 6 days with unknown Group B Strep (GBS) status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Induction of Labor (IOL) to Delivery | Time (hours) from start of IOL (As defined by receipt of first medication for induction of labor) to delivery of infant. | Time (hours) from start of IOL (As defined by receipt of first medication for induction of labor) to delivery of infant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Premature Rupture of Membranes (PROM) to Delivery | Time (hours) from PROM (as reported by patient) to delivery of infant | — |
| Time From IOL to Vaginal Delivery | Time from IOL (as defined by receipt of first medication for induction) to vaginal delivery | — |
| Time From PROM to Vaginal Delivery | Time (hours) from PROM (as reported by patient) to vaginal delivery | — |
| Infection | Enrollment to Delivery | Suspected intraamniotic infection |
| Maternal Morbidity | Enrollment to 4 weeks postpartum | Composite maternal morbidity: postpartum hemorrhage, blood transfusion, endometritis, wound infection, venous thromboembolism (VTE), hysterectomy, Intensive care unit (ICU) admission, readmission within 4 weeks, death |
| Neonatal Morbidity | Enrollment to hospital discharge (On average 2-4 days) | Composite neonatal morbidity: NICU admission \> 48 hours, neonatal blood transfusion, hypoxic ischemic encephalopathy, intraventricular hemorrhage grade III or IV, headcooling, severe respiratory distress syndrome, necrotizing enterocolitis, sepsis, death |
| Cesarean Delivery | Enrollment to Delivery | Cesarean section rate |
Countries
United States
Participant flow
Recruitment details
Began: August 2019 End: May 2023 (Last participant follow-up completed 1/8/2023. Additional subjects were screened/approached for participation through 5/2023.) Location: Labor and Delivery
Participants by arm
| Arm | Count |
|---|---|
| Oral Misoprostol Misoprostol: Oral misoprostol 50 mcg every 4 hours for up to 6 doses or until cervical ripening is no longer indicated | 52 |
| Oxytocin Oxytocin: IV Oxytocin 2 milliunits (mU)/min, increased by 2mU/min q15 minutes per hospital protocol. Max 40 mU/min | 56 |
| Total | 108 |
Baseline characteristics
| Characteristic | Total | Oral Misoprostol | Oxytocin |
|---|---|---|---|
| Age, Continuous | 29.2 years STANDARD_DEVIATION 5.7 | 30.0 years STANDARD_DEVIATION 5.4 | 28.5 years STANDARD_DEVIATION 5.9 |
| BMI | 31.9 kg/m^2 | 31.9 kg/m^2 | 31.9 kg/m^2 |
| Gestational age at Rupture of Membranes | 39.4 Weeks | 39.7 Weeks | 39.3 Weeks |
| Prenatal Visit Number | 9 Visits | 9 Visits | 9 Visits |
| Public Insurance | 43 Participants | 20 Participants | 23 Participants |
| Race/Ethnicity, Customized Race Asian | 10 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Black | 52 Participants | 27 Participants | 25 Participants |
| Race/Ethnicity, Customized Race Hispanic, not otherwise specified | 6 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 40 Participants | 20 Participants | 20 Participants |
| Region of Enrollment United States | 108 Participants | 52 Participants | 56 Participants |
| Sex: Female, Male Female | 108 Participants | 52 Participants | 56 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Starting Bishop Score | 3.8 Units on a scale. STANDARD_DEVIATION 1.6 | 3.6 Units on a scale. STANDARD_DEVIATION 1.5 | 3.9 Units on a scale. STANDARD_DEVIATION 1.7 |
| Starting Cervical Dilation | 1.1 Centimeters STANDARD_DEVIATION 0.5 | 1.1 Centimeters STANDARD_DEVIATION 0.6 | 1.1 Centimeters STANDARD_DEVIATION 0.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 56 | 0 / 52 | 0 / 56 |
| other Total, other adverse events | 3 / 52 | 3 / 56 | 1 / 52 | 2 / 56 |
| serious Total, serious adverse events | 0 / 52 | 0 / 56 | 1 / 52 | 0 / 56 |
Outcome results
Primary
Time From Induction of Labor (IOL) to Delivery
Time (hours) from start of IOL (As defined by receipt of first medication for induction of labor) to delivery of infant.
Time frame: Time (hours) from start of IOL (As defined by receipt of first medication for induction of labor) to delivery of infant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Misoprostol | Time From Induction of Labor (IOL) to Delivery | 18.1 Hours |
| Oxytocin | Time From Induction of Labor (IOL) to Delivery | 14.9 Hours |
Secondary
Cesarean Delivery
Cesarean section rate
Time frame: Enrollment to Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Misoprostol | Cesarean Delivery | 13 Participants |
| Oxytocin | Cesarean Delivery | 14 Participants |
Secondary
Infection
Suspected intraamniotic infection
Time frame: Enrollment to Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Misoprostol | Infection | 8 Participants |
| Oxytocin | Infection | 6 Participants |
Secondary
Maternal Morbidity
Composite maternal morbidity: postpartum hemorrhage, blood transfusion, endometritis, wound infection, venous thromboembolism (VTE), hysterectomy, Intensive care unit (ICU) admission, readmission within 4 weeks, death
Time frame: Enrollment to 4 weeks postpartum
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Misoprostol | Maternal Morbidity | 8 Participants |
| Oxytocin | Maternal Morbidity | 9 Participants |
Secondary
Neonatal Morbidity
Composite neonatal morbidity: NICU admission \> 48 hours, neonatal blood transfusion, hypoxic ischemic encephalopathy, intraventricular hemorrhage grade III or IV, headcooling, severe respiratory distress syndrome, necrotizing enterocolitis, sepsis, death
Time frame: Enrollment to hospital discharge (On average 2-4 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Misoprostol | Neonatal Morbidity | 1 Participants |
| Oxytocin | Neonatal Morbidity | 2 Participants |
Secondary
Time From IOL to Vaginal Delivery
Time frame: Time from IOL (as defined by receipt of first medication for induction) to vaginal delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Misoprostol | Time From IOL to Vaginal Delivery | 17.9 Hours |
| Oxytocin | Time From IOL to Vaginal Delivery | 12.9 Hours |
Secondary
Time From Premature Rupture of Membranes (PROM) to Delivery
Time frame: Time (hours) from PROM (as reported by patient) to delivery of infant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Misoprostol | Time From Premature Rupture of Membranes (PROM) to Delivery | 25.8 Hours |
| Oxytocin | Time From Premature Rupture of Membranes (PROM) to Delivery | 22.1 Hours |
Secondary
Time From PROM to Vaginal Delivery
Time frame: Time (hours) from PROM (as reported by patient) to vaginal delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Misoprostol | Time From PROM to Vaginal Delivery | 24.9 Hours |
| Oxytocin | Time From PROM to Vaginal Delivery | 21.6 Hours |