Propranolol for Protracted Labor (PRO-Labor)
Primary Purpose
Labour;Obstructed, Labor Dystocia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Propranolol
Sponsored by
About this trial
This is an interventional treatment trial for Labour;Obstructed
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.
Sites / Locations
- Christiana Care
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Propranolol 2mg IV
No intervention
Arm Description
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.
At the time of labor dystocia, patients randomized to the placebo arm will not receive any intervention
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
cesarean delivery rate
rate of cesarean delivery
maternal length of stay
from time of admission to discharge
Maternal Bradycardia event
bradycardia alert during labor
Chorioamnionitis
defined by the presence of maternal fever ≥100·4°f in the presence of maternal or fetal tachycardia or fundal tenderness
neonatal admission to ICU
NICU admission
Severe respiratory distress syndrome
defined as intubation and mechanical ventilation for a minimum of 12 hours
neonatal sepsis
Culture proven-presumed neonatal sepsis
Neonatal blood transfusion
Neonatal blood transfusion
Hypoxic ischemic encephalopathy
neonatal HIE
Full Information
NCT ID
NCT04741698
First Posted
January 15, 2021
Last Updated
July 26, 2022
Sponsor
Christiana Care Health Services
1. Study Identification
Unique Protocol Identification Number
NCT04741698
Brief Title
Propranolol for Protracted Labor
Acronym
PRO-Labor
Official Title
Propranolol for Prolonged Labor: A Randomized Controlled Trial (PRO-Labor Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
July 27, 2021 (Actual)
Primary Completion Date
June 11, 2022 (Actual)
Study Completion Date
July 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Christiana Care Health Services
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Labour;Obstructed, Labor Dystocia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Propranolol 2mg IV
Arm Type
Active Comparator
Arm Description
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.
Arm Title
No intervention
Arm Type
No Intervention
Arm Description
At the time of labor dystocia, patients randomized to the placebo arm will not receive any intervention
Intervention Type
Drug
Intervention Name(s)
Propranolol
Other Intervention Name(s)
Propranolol Hydrochloride, Inderal, Inderal LA, InnoPran XL, Hemangeol
Intervention Description
Propranolol 2mg IV
Primary Outcome Measure Information:
Title
time to delivery
Description
The primary outcome is time to delivery (hours) defined as time from initiation of induction method to delivery time, regardless of mode of delivery.
Time Frame
Number of hours from induction to delivery of neonate; up to 72 hours.
Secondary Outcome Measure Information:
Title
cesarean delivery rate
Description
rate of cesarean delivery
Time Frame
At time of delivery
Title
maternal length of stay
Description
from time of admission to discharge
Time Frame
From time of admission to time of hospital discharge; an average of two days
Title
Maternal Bradycardia event
Description
bradycardia alert during labor
Time Frame
at time of delivery
Title
Chorioamnionitis
Description
defined by the presence of maternal fever ≥100·4°f in the presence of maternal or fetal tachycardia or fundal tenderness
Time Frame
At time of delivery
Title
neonatal admission to ICU
Description
NICU admission
Time Frame
At time of delivery
Title
Severe respiratory distress syndrome
Description
defined as intubation and mechanical ventilation for a minimum of 12 hours
Time Frame
at time of delivery
Title
neonatal sepsis
Description
Culture proven-presumed neonatal sepsis
Time Frame
at time of delivery
Title
Neonatal blood transfusion
Description
Neonatal blood transfusion
Time Frame
From time of delivery to time of hospital discharge; up to 6 weeks
Title
Hypoxic ischemic encephalopathy
Description
neonatal HIE
Time Frame
through study completion, an average of 1 year
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen B Gomez, MD
Organizational Affiliation
Christiana Care Health Services
Official's Role
Principal Investigator
Facility Information:
Facility Name
Christiana Care
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24392402
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. Erratum In: J Clin Diagn Res. 2015 Aug;9(8):ZZ01.
Results Reference
background
PubMed Identifier
18588611
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.
Results Reference
background
PubMed Identifier
26695642
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.
Results Reference
background
PubMed Identifier
573555
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.
Results Reference
background
PubMed Identifier
8841209
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.
Results Reference
background
PubMed Identifier
22815467
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.
Results Reference
background
PubMed Identifier
16051416
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.
Results Reference
background
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Propranolol for Protracted Labor
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