Propranolol for Protracted Labor (PRO-Labor)

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

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.

Study Overview

• Status: Completed
• Conditions: Labour;Obstructed; Labor Dystocia
• Intervention / Treatment: Drug: Propranolol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propranolol 2mg IV; 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; Propranolol 2mg IV; Other Names: Inderal; Hemangeol; Propranolol Hydrochloride; Inderal LA; InnoPran XL
No Intervention: No intervention; At the time of labor dystocia, patients randomized to the placebo arm will not receive any intervention

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: Christiana Care Health Services

Publications and helpful links

General Publications

• Moghadam AD, Jaafarpour M, Khani A. Comparison effect of oral propranolol and oxytocin versus oxytocin only on induction of labour in nulliparous women (a double blind randomized trial). J Clin Diagn Res. 2013 Nov;7(11):2567-9. doi: 10.7860/JCDR/2013/5704.3613. Epub 2013 Nov 10. Erratum In: J Clin Diagn Res. 2015 Aug;9(8):ZZ01.
• Kashanian M, Fekrat M, Zarrin Z, Ansari NS. A comparison between the effect of oxytocin only and oxytocin plus propranolol on the labor (a double blind randomized trial). J Obstet Gynaecol Res. 2008 Jun;34(3):354-8. doi: 10.1111/j.1447-0756.2008.00790.x.
• Pergialiotis V, Frountzas M, Prodromidou A, Prapa S, Perrea DN, Vlachos GD. Propranolol and oxytocin versus oxytocin alone for induction and augmentation of labor: a meta-analysis of randomized trials. Arch Gynecol Obstet. 2016 Apr;293(4):721-9. doi: 10.1007/s00404-015-3991-8. Epub 2015 Dec 22.
• Pruyn SC, Phelan JP, Buchanan GC. Long-term propranolol therapy in pregnancy: maternal and fetal outcome. Am J Obstet Gynecol. 1979 Oct 15;135(4):485-9. doi: 10.1016/0002-9378(79)90436-8.
• Sanchez-Ramos L, Quillen MJ, Kaunitz AM. Randomized trial of oxytocin alone and with propranolol in the management of dysfunctional labor. Obstet Gynecol. 1996 Oct;88(4 Pt 1):517-20. doi: 10.1016/0029-7844(96)00223-2.
• Meidahl Petersen K, Jimenez-Solem E, Andersen JT, Petersen M, Brodbaek K, Kober L, Torp-Pedersen C, Poulsen HE. beta-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study. BMJ Open. 2012 Jul 19;2(4):e001185. doi: 10.1136/bmjopen-2012-001185. Print 2012.
• Palomaki O, Uotila J, Tammela O, Kaila T, Lavapuro M, Huhtala H, Tuimala R. A double blind, randomized trial on augmentation of labour with a combination of intravenous propranolol and oxytocin versus oxytocin only. Eur J Obstet Gynecol Reprod Biol. 2006 Mar 1;125(1):44-9. doi: 10.1016/j.ejogrb.2005.06.016. Epub 2005 Jul 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Actual): June 11, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Dystocia; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: DDD# 604829

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No