Propranolol for Protracted Labor

Study Overview
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Brief Summary
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Induction of labor is one of the most common procedures performed on labor and delivery. In the United States, more than 20 percent of pregnant women undergo an induction of labor [1]. There is data from small, randomized studies that demonstrates the effectiveness of propranolol, a non-selective beta-blocker, for labor augmentation. 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 [2-8]. Alpha- and beta-adrenergic receptors have been identified in the human myometrium. Propranolol has been shown in studies to enhance uterine contractions and may be a useful tool in this population of women. Therefore, the purpose of this study is to assess whether the administration of propranolol at time of labor dystocia reduces time to delivery.

Detailed Description
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All cervical ripening will be performed in the labor and delivery unit; continuous fetal heart rate and uterine activity will be monitored in all patients. Cervical dilation is assigned by admitting physicians. Sonography will be performed to document fetal presentation. At the time of prolonged labor, patients meeting inclusion criteria and no exclusion criteria will be consented. There will be no monetary incentives for participation. Patients will be randomized to either Propranolol 2mg of IV or expectant management at the time of induction. Maternal vitals will be collected per standard labor management. Episodes of uterine activity that are deemed excessive by the physician will be treated with a standard combination of maneuvers that included a change in maternal position, oxygen administration, and terbutaline 250 µg subcutaneously. Persistent abnormal fetal heart rate patterns resulted in intervention by removing the patient from the study. Urgent cesarean delivery is defined as a cesarean delivery performed during the ripening process for abnormal fetal heart rate that did not respond to standard maneuvers.

Official Title
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Propranolol for Prolonged Labor: A Randomized Controlled Trial (PRO-Labor Trial)

Conditions
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Labour;Obstructed, Labor Dystocia

Intervention / Treatment
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* Drug: Propranolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age full term (≥37 weeks) gestations determined by routine obstetrical guidelines singleton gestation in cephalic presentation Intact membranes Bishop score of ≤6 and cervical dilation ≤2cm Exclusion Criteria: Preterm gestation Diabetes requiring insulin in labor: given the potential risk of neonatal hypoglycemia in the neonate multiparous women Any cardiac condition for which β blockade is contraindicated (cardiogenic shock, sinus bradycardia, and greater than first degree heart block) Known hypersensitivity to propranolol Maternal bradycardia (HR <60bpm) Severe preeclampsia: as patients will be receiving magnesium and possibly labetalol for hypertension control Systolic blood pressure <90 mmHg, or diastolic blood pressure <50 mmHg Receiving other beta blocker Moderate or severe asthma: as this is a contraindication to beta blocker use Any contraindication to a vaginal delivery fetal demise Multifetal gestation major fetal anomaly prior uterine surgery, previous cesarean section women with HIV, hepatitis C, hepatitis B, and women with medical conditions requiring an assisted second stage Additional exclusion criteria were as follows: category 3 fetal heart rate tracing, hemolysis elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia, growth restriction <10th percentile (based on Hadlock growth curves) with reversal of flow in umbilical artery Doppler studies, and growth restriction <5th percentile with elevated, absent, or reversal of flow in umbilical artery Doppler studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propranolol 2mg IV<br>At the time of labor dystocia, patients randomized to the treatment arm of propranolol will receive a one-time administration of IV 2mg propranolol in pre-mixed syringes prepared by the pharmacy. The propranolol IV administration recommended in clinical practice guidelines is 1 mg IV over 1 minute. Therefore, total administration time will be 2 minutes. | Drug: Propranolol<br>* Propranolol 2mg IV<br>* Other names: Hemangeol;|
| No Intervention: No intervention<br>At the time of labor dystocia, patients randomized to the placebo arm will not receive any intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to delivery | The primary outcome is time to delivery (hours) defined as time from initiation of induction method to delivery time, regardless of mode of delivery. | Number of hours from induction to delivery of neonate; up to 72 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cesarean delivery rate | rate of cesarean delivery | At time of delivery | 
| maternal length of stay | from time of admission to discharge | From time of admission to time of hospital discharge; an average of two days | 
| Maternal Bradycardia event | bradycardia alert during labor | at time of delivery | 
| Chorioamnionitis | defined by the presence of maternal fever ≥100·4°f in the presence of maternal or fetal tachycardia or fundal tenderness | At time of delivery | 
| neonatal admission to ICU | NICU admission | At time of delivery | 
| Severe respiratory distress syndrome | defined as intubation and mechanical ventilation for a minimum of 12 hours | at time of delivery | 
| neonatal sepsis | Culture proven-presumed neonatal sepsis | at time of delivery | 
| Neonatal blood transfusion | Neonatal blood transfusion | From time of delivery to time of hospital discharge; up to 6 weeks | 
| Hypoxic ischemic encephalopathy | neonatal HIE | through study completion, an average of 1 year |