I.V Papavrine for Labor Induction in Term PROM

I.V Papavrine for Labor Induction in Term PROM: A Prospective Randomized Controlled Trial

This prospective randomized controlled trial aims to evaluate whether intravenous administration of papaverine 12 hours after term PROM reduces the interval from membrane rupture to delivery and improves maternal and neonatal outcomes. Researchers will compare drug papaverine to a placebo

Study Overview

• Status: Recruiting
• Conditions: Premature Rupture of Membranes
• Intervention / Treatment: Drug: Papaverine arm; Other: Placebo

Detailed Description

Prelabor rupture of membranes (PROM) at term complicates approximately 8% of pregnancies and is associated with increasing maternal and neonatal infectious morbidity as the latency period to delivery lengthens. Consequently, most clinical guidelines recommend active management with labor induction within 24 hours following membrane rupture. Cervical status at the time of induction plays a critical role in labor outcomes, and women with an unfavorable cervix, commonly defined as a Bishop score below 8, are at increased risk of prolonged labor and induction failure. The uterine cervix is composed primarily of connective tissue, with smooth muscle accounting for approximately 15% of its structure and concentrated mainly beneath the internal cervical os. Papaverine is a musculotropic antispasmodic agent that acts directly on smooth muscle, leading to reduced muscle spasm and enhanced relaxation. The pharmacokinetic profile of papaverine includes a rapid onset of action within approximately 10 minutes and a short half-life of 0.5-2 hours, making it a potentially suitable adjunct during early labor. Antispasmodic agents have been shown to accelerate cervical dilatation and shorten the first stage of labor; however, their role in the management of term PROM has not been systematically evaluated. We therefore aim to investigate whether intravenous administration of papaverine in women with term PROM shortens the interval from membrane rupture to delivery and improves cervical ripening and maternal and neonatal outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maya Frank Wolf, professor; Phone Number: • 972:50-7887800; Email: mayaw@gmc.gov.il

Study Locations

• Israel
  • Israel
    • Nahariya, Israel, Israel
      • Recruiting
      • Galilee Medical Center
      • Contact: Maya Frank Wolf, professor; Phone Number: +972507887800; Email: mayaw@gmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• • Singleton pregnancy

  • Term gestation (37-42 weeks)
  • Term PROM prior to active labor
  • Duration of PROM <12 hours at enrollment
  • Bishop score <8
  • Cephalic presentation
  • Viable fetus with reassuring fetal heart rate

Exclusion Criteria:

• • Multiple gestation

  • Previous cesarean delivery
  • Major fetal anomalies
  • Contraindication to vaginal delivery
  • Meconium-stained amniotic fluid
  • Suspected chorioamnionitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: papaverine arm; IV-papaverine 80 mg in 100 ml 0.9% saline, once, 12 hours after rupture of membranes	Drug: Papaverine arm; given 12 houres after rupture of membranes
Placebo Comparator: Control arm; I.V 100 ml 0.9% saline, 12 hours after rupture of membranes	Other: Placebo; I.V seline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time interval from rupture of membranes to delivery	Time from rupture of membrane to delivery, measured in hours, including pre and post intervention periods	up to 5 days from rupture of membranes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in bishop score following intervention	Bishop score messured at admission and 18 houres after rupture of membranes, and comparing the delta bishop scores between the groups	baseline to 6-12 hours after intervention
mode of delivary	Mode of delivery categorized as vaginal (spontaneous or operative) or cesarean delivery	At delivery/birth

Collaborators and Investigators

• Sponsor: Western Galilee Hospital-Nahariya

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2025
• Primary Completion (Estimated): October 22, 2027
• Study Completion (Estimated): October 22, 2027

Study Registration Dates

• First Submitted: January 7, 2026
• First Submitted That Met QC Criteria: April 3, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: papaverine; premature rupture of membranes; bishop score
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: 0152-25-NHR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The authors are willing to share the data of the study upon request of the Editors.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No