Clinical trial NCT04741698: Propranolol for Protracted Labor
Official title: Propranolol for Prolonged Labor: A Randomized Controlled Trial (PRO-Labor Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Labour;Obstructed
Labor Dystocia
Lead sponsor: Christiana Care Health Services
Sponsor class: OTHER
First posted: 2021-02-05
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: time to delivery
timeFrame: Number of hours from induction to delivery of neonate; up to 72 hours.
Secondary outcomes:
measure: cesarean delivery rate
timeFrame: At time of delivery
measure: maternal length of stay
timeFrame: From time of admission to time of hospital discharge; an average of two days
measure: Maternal Bradycardia event
timeFrame: at time of delivery
measure: Chorioamnionitis
timeFrame: At time of delivery
measure: neonatal admission to ICU
timeFrame: At time of delivery
measure: Severe respiratory distress syndrome
timeFrame: at time of delivery
measure: neonatal sepsis
timeFrame: at time of delivery
measure: Neonatal blood transfusion
timeFrame: From time of delivery to time of hospital discharge; up to 6 weeks
measure: Hypoxic ischemic encephalopathy
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Newark
country: United States
facility: Christiana Care
state: Delaware
Study officials:
affiliation: Christiana Care Health Services
name: Helen B Gomez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.