Induction of Labor Affected Fetus / Newborn
Conditions
Keywords
Induction, Labor, Propranolol
Brief summary
A randomized, prospective trial will be offered to women admitted to the labor floors at Mount Sinai Medical Center for labor induction.
Detailed description
Induction of labor is a common obstetric procedure, which is performed to provoke the onset of labor and lead to delivery of the fetus. While some early studies suggested a possible increased rate of cesarean with induction of labor, more recent meta-analyses have shown that induction does not influence this rate. There is data from small randomized studies that demonstrates the effectiveness of propranolol, a non-selective beta-blocker, for induction of labor. This literature suggests a decrease in the amount of time to delivery and a possible reduction in cesarean section rates when propranolol is used in conjunction with oxytocin for induction of labor compared to oxytocin alone.
Interventions
DRUGPropranolol
After induction is started with Foley or misoprostol placement, 30 minutes will pass before administration of the one-time study medication, IV Propanolol.
DRUGPlacebo
After induction is started with Foley or misoprostol placement, 30 minutes will pass before administration of IV Saline
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study drug and placebo will be randomized and mixed to appear identical by the Mount Sinai Investigational Drug Service (IDS). The randomization code will be kept by the lead pharmacist of the IDS until completion of the trial, at which point data will be unmasked.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Nulliparous women undergoing induction of labor * \>37 weeks' gestational age * Non-anomalous, singleton cephalic presenting fetus.
Exclusion criteria
* Multiple gestations, known fetal anomalies * Maternal cardiac or hypertensive disease * Chronic beta blocker use * Bronchial asthma * Maternal or fetal indication for immediate delivery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Beginning of Induction to Delivery | average of 24 hours | The time of induction (based on time of foley balloon placement for cervical ripening or misoprostol administration) to the time of delivery of the infant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Latent | average of 24 hours | Time of latent labor defined as \<6cm of cervical dilation. |
| Number of Participants With Maternal Morbidity Composite Score = 1 | average of 24 hours | Composite maternal morbidity score consists of a count of postpartum hemorrhage, transfusion, hysterectomy, placental abruption, chorioamnionitis, shoulder dystocia, episiotomy, higher order laceration, and ICU admission. The composite score was computed as a score of 1 for any indication of maternal morbidity, that is the participant experienced at least one maternal morbidity, and the components are given equal weights. Participants who had no evidence of the predefined maternal morbidities are subsequently given a score of 0. The minimum is 0 and maximum is 1. |
| Number of Participants With Postpartum Hemorrhage | 30 minutes from drug administration | Greater than 500cc of blood expelled during a vaginal delivery or greater than 1000cc of blood expelled during a cesarean section |
| Number of Participants With Various Mode of Delivery | average of 24 hours | Number of various mode of delivery - count of Vaginal delivery, vacuum assisted vaginal delivery, forceps assisted vaginal delivery, cesarean section |
| Number of Fetus With Fetal Bradycardia | 30 minutes from drug administration | Count of fetus with fetal bradycardia (\<110bpm for \>10 minutes within 30 minutes of study drug administration) |
| Number of Neonates With Neonatal Outcome Composite Score = 1 | Day 1 | Composite neonatal outcome score was for any of the following morbidity: Neonatal Intensive Care Unit (NICU) admission, respiratory support (CPAP, nasal cannula, intubation), culture proven sepsis, radiographically proven intracranial hemorrhage, necrotizing enterocolitis, hypoglycemia (for those infants who had sugar checked), and neonatal death. The composite score was computed as a score of 1 for any indication of neonatal morbidity - neonates who experienced at least one morbidity and the components are given equal weights. Patients who had no evidence of the predefined neonatal morbidities are subsequently given a score of 0. The minimum is 0 and maximum is 1. |
| Number of Neonates With Hypoglycemia | Day 1 | Neonatal outcome - Number of neonates with hypoglycemia (blood glucose \<50). This population includes only the neonates who had heelsticks to check their blood glucose, which is not a universal practice and was not required by the protocol or IRB. The neonates included were those who met the nursery's risk-based protocol to check blood glucose after birth (ex: infants of diabetic mothers, fetal growth restriction, macrosomia, or symptoms suggestive of hypoglycemia) |
| Number of Fetus With Heart Rate Decelerations | 30 minutes from drug administration | Count of fetus with fetal heart rate decelerations within 30 minutes of study drug administration |
Countries
United States
Participant flow
Recruitment details
First enrollment 12-11-2017, final enrollment 12/11/2018. Enrollment occurred on the labor floor of the Mount Sinai Hospital.
Participants by arm
| Arm | Count |
|---|---|
| Propranolol After induction was started with Foley or misoprostol placement, 30 minutes passed before administration of propranolol 2mg of IV push | 121 |
| Placebo After induction was started with Foley or misoprostol placement, 30 minutes passed before administration of an equivalent quantity in milliliters of IV normal saline | 119 |
| Total | 240 |
Baseline characteristics
| Characteristic | Total | Placebo | Propranolol |
|---|---|---|---|
| Age, Continuous | 31.66 years STANDARD_DEVIATION 6.04 | 31.61 years STANDARD_DEVIATION 6.37 | 31.70 years STANDARD_DEVIATION 5.72 |
| Body Mass Index (BMI) at admission | 28.97 kg/m^2 STANDARD_DEVIATION 4.89 | 28.89 kg/m^2 STANDARD_DEVIATION 4.4 | 29.04 kg/m^2 STANDARD_DEVIATION 5.34 |
| Fetal Growth Restriction | 11 Participants | 3 Participants | 8 Participants |
| Gestational Age (GA) at admission | 40.0 months | 40.1 months | 39.7 months |
| In vitro Fertilization (IVF) | 37 Participants | 19 Participants | 18 Participants |
| Married | 191 Participants | 97 Participants | 94 Participants |
| Private Insurance | 194 Participants | 93 Participants | 101 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 11 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 37 Participants | 20 Participants | 17 Participants |
| Race (NIH/OMB) White | 155 Participants | 83 Participants | 72 Participants |
| Sex: Female, Male Female | 240 Participants | 119 Participants | 121 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tobacco Use | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 121 | 0 / 119 |
| other Total, other adverse events | 16 / 121 | 13 / 119 |
| serious Total, serious adverse events | 1 / 121 | 0 / 119 |
Outcome results
Primary
Time From Beginning of Induction to Delivery
The time of induction (based on time of foley balloon placement for cervical ripening or misoprostol administration) to the time of delivery of the infant.
Time frame: average of 24 hours
Population: N=154 - only those who delivered vaginally
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Time From Beginning of Induction to Delivery | 13.8 hours | Standard Deviation 5.4 |
| Placebo | Time From Beginning of Induction to Delivery | 14.3 hours | Standard Deviation 5.3 |
Secondary
Duration of Latent
Time of latent labor defined as \<6cm of cervical dilation.
Time frame: average of 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Duration of Latent | 11.0 hours | Standard Deviation 5 |
| Placebo | Duration of Latent | 11.2 hours | Standard Deviation 4.5 |
Secondary
Number of Fetus With Fetal Bradycardia
Count of fetus with fetal bradycardia (\<110bpm for \>10 minutes within 30 minutes of study drug administration)
Time frame: 30 minutes from drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Fetus With Fetal Bradycardia | 1 Participants |
| Placebo | Number of Fetus With Fetal Bradycardia | 0 Participants |
Secondary
Number of Fetus With Heart Rate Decelerations
Count of fetus with fetal heart rate decelerations within 30 minutes of study drug administration
Time frame: 30 minutes from drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Fetus With Heart Rate Decelerations | 15 Participants |
| Placebo | Number of Fetus With Heart Rate Decelerations | 13 Participants |
Secondary
Number of Neonates With Hypoglycemia
Neonatal outcome - Number of neonates with hypoglycemia (blood glucose \<50). This population includes only the neonates who had heelsticks to check their blood glucose, which is not a universal practice and was not required by the protocol or IRB. The neonates included were those who met the nursery's risk-based protocol to check blood glucose after birth (ex: infants of diabetic mothers, fetal growth restriction, macrosomia, or symptoms suggestive of hypoglycemia)
Time frame: Day 1
Population: This population includes the neonates who had heelsticks to check their blood glucose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Neonates With Hypoglycemia | 11 Participants |
| Placebo | Number of Neonates With Hypoglycemia | 8 Participants |
Secondary
Number of Neonates With Neonatal Outcome Composite Score = 1
Composite neonatal outcome score was for any of the following morbidity: Neonatal Intensive Care Unit (NICU) admission, respiratory support (CPAP, nasal cannula, intubation), culture proven sepsis, radiographically proven intracranial hemorrhage, necrotizing enterocolitis, hypoglycemia (for those infants who had sugar checked), and neonatal death. The composite score was computed as a score of 1 for any indication of neonatal morbidity - neonates who experienced at least one morbidity and the components are given equal weights. Patients who had no evidence of the predefined neonatal morbidities are subsequently given a score of 0. The minimum is 0 and maximum is 1.
Time frame: Day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Neonates With Neonatal Outcome Composite Score = 1 | 21 Participants |
| Placebo | Number of Neonates With Neonatal Outcome Composite Score = 1 | 28 Participants |
Secondary
Number of Participants With Maternal Morbidity Composite Score = 1
Composite maternal morbidity score consists of a count of postpartum hemorrhage, transfusion, hysterectomy, placental abruption, chorioamnionitis, shoulder dystocia, episiotomy, higher order laceration, and ICU admission. The composite score was computed as a score of 1 for any indication of maternal morbidity, that is the participant experienced at least one maternal morbidity, and the components are given equal weights. Participants who had no evidence of the predefined maternal morbidities are subsequently given a score of 0. The minimum is 0 and maximum is 1.
Time frame: average of 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Participants With Maternal Morbidity Composite Score = 1 | 35 Participants |
| Placebo | Number of Participants With Maternal Morbidity Composite Score = 1 | 49 Participants |
Secondary
Number of Participants With Postpartum Hemorrhage
Greater than 500cc of blood expelled during a vaginal delivery or greater than 1000cc of blood expelled during a cesarean section
Time frame: 30 minutes from drug administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Propranolol | Number of Participants With Postpartum Hemorrhage | 15 Participants |
| Placebo | Number of Participants With Postpartum Hemorrhage | 26 Participants |
Secondary
Number of Participants With Various Mode of Delivery
Number of various mode of delivery - count of Vaginal delivery, vacuum assisted vaginal delivery, forceps assisted vaginal delivery, cesarean section
Time frame: average of 24 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Propranolol | Number of Participants With Various Mode of Delivery | Spontaneous vaginal delivery | 64 Participants |
| Propranolol | Number of Participants With Various Mode of Delivery | Vacuum assisted vaginal delivery | 3 Participants |
| Propranolol | Number of Participants With Various Mode of Delivery | Forceps assisted vaginal delivery | 8 Participants |
| Propranolol | Number of Participants With Various Mode of Delivery | Cesarean section | 46 Participants |
| Placebo | Number of Participants With Various Mode of Delivery | Cesarean section | 40 Participants |
| Placebo | Number of Participants With Various Mode of Delivery | Spontaneous vaginal delivery | 61 Participants |
| Placebo | Number of Participants With Various Mode of Delivery | Forceps assisted vaginal delivery | 8 Participants |
| Placebo | Number of Participants With Various Mode of Delivery | Vacuum assisted vaginal delivery | 10 Participants |