Intravenous Papaverine for Term Prelabor Rupture of Membranes

The Effect of Papaverine on Labour in Term Premature Rupture of Membranes (PROM)

This randomized, double-blind, placebo-controlled trial evaluates whether intravenous papaverine, administered as an adjunct to oxytocin, shortens the time to delivery in women with term premature rupture of membranes (PROM). Participants are randomized in a 1:1 ratio to receive either intravenous papaverine 80 mg in 100 mL of 0.9% saline or 100 mL of 0.9% saline as placebo, administered one hour after initiation of oxytocin. The primary outcome is the interval from study infusion to delivery. Secondary outcomes include mode of delivery and maternal and neonatal outcomes.

Study Overview

• Status: Recruiting
• Conditions: Premature Rupture of Fetal Membranes
• Intervention / Treatment: Drug: Papaverine; Drug: Normal Saline Placebo Infusion

Detailed Description

Women hospitalized in the labor and delivery unit with term premature rupture of membranes at 37 weeks of gestation or later are screened for participation. Eligible participants have no active contractions, cervical dilation of less than 2 cm, vertex presentation, and a duration of membrane rupture between 2 and 12 hours.

Following informed consent, participants are randomized in a 1:1 ratio to receive intravenous papaverine 80 mg diluted in 100 mL of 0.9% saline or 100 mL of 0.9% saline as placebo. The study infusion is administered one hour after initiation of oxytocin.

Treatment allocation is blinded. One study-team member prepares the study solution according to the randomization table, while the remainder of the study team remains blinded to treatment allocation. The primary outcome is the interval from study infusion to delivery.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ornit Cohen; Phone Number: +972-3-5028399; Email: ornitc@wmc.gov.il
• Study Contact Backup: Name: Eliel Kedar Sade, MD; Phone Number: +972-52-6008068; Email: elielbob@gmaill.com

Study Locations

• Israel
  • Holon, Israel, 5822012
    • Recruiting
    • The Edith Wolfson Medical Center
    • Contact: Ornit Cohen; Phone Number: +972-3-5028399; Email: ornitc@wmc.gov.il
    • Contact: Eliel Kedar Sade, MD; Phone Number: +972-52-6008068; Email: elielbob@gmaill.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Gestational age ≥37 weeks with term PROM
• No active contractions
• Cervical dilation <2 cm
• Vertex presentation
• PROM duration between 2 and 12 hours

Exclusion Criteria:

• Previous cesarean delivery
• Contraindication to vaginal delivery
• Known fetal malformation
• Known allergy to papaverine
• Cardiac arrhythmia
• Glaucoma
• Hepatitis or other hepatic disease
• Atrioventricular (AV) block
• Congestive heart disease
• Recent ischemic heart disease
• Increased intracranial pressure
• Active labor, defined as cervical dilation ≥6 cm
• Contraindication to uterine relaxation, including significant uterine bleeding or fetal distress Active infection or chorioamnionitis Use of medications with potentially hazardous interactions with papaverine

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Papaverine; Participants received intravenous papaverine 80 mg diluted in 100 mL of 0.9% normal saline.	Drug: Papaverine; Papaverine 80 mg diluted in 100 mL of 0.9% normal saline, administered intravenously as a single study infusion.
Placebo Comparator: Placebo; Participants received 100 mL of intravenous 0.9% normal saline as placebo.	Drug: Normal Saline Placebo Infusion; 100 mL of 0.9% normal saline, administered intravenously as a single placebo study infusion.; Other Names: 0.9% Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Study Infusion to Delivery	Time, measured in hours, from administration of the assigned study infusion (papaverine or placebo) to delivery.	From administration of the study infusion until delivery, assessed up to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mode of Delivery	Mode of delivery, categorized as vaginal or cesarean delivery	From rupture of membranes until delivery, assessed up to 48 hours
Maternal Infectious Complications	Proportion of participants with maternal infectious complications	From rupture of membranes until delivery, assessed up to 48 hours
Postpartum Hemorrhage	Proportion of participants with postpartum hemorrhage	From rupture of membranes until delivery, assessed up to 48 hours
Apgar Score at 5 Minutes	Apgar score recorded 5 minutes after birth, ranging from 0 to 10	5 minutes after birth
Umbilical Cord pH Below 7.1	Proportion of neonates with umbilical cord blood pH below 7.1	At birth, based on umbilical artery cord blood sampling
Neonatal Infection	Proportion of neonates diagnosed with neonatal infection	From birth through neonatal hospital discharge, assessed up to 7 days after birth

Collaborators and Investigators

• Sponsor: Wolfson Medical Center

Publications and helpful links

General Publications

• Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.
• Rohwer AC, Khondowe O, Young T. Antispasmodics for labour. Cochrane Database Syst Rev. 2013 Jun 5;2013(6):CD009243. doi: 10.1002/14651858.CD009243.pub3.
• Middleton P, Shepherd E, Flenady V, McBain RD, Crowther CA. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev. 2017 Jan 4;1(1):CD005302. doi: 10.1002/14651858.CD005302.pub3.
• Singh KC, Jain P, Goel N, Saxena A. Drotaverine hydrochloride for augmentation of labor. Int J Gynaecol Obstet. 2004 Jan;84(1):17-22. doi: 10.1016/s0020-7292(03)00276-5.
• Abu Shqara R, Nakhleh Francis Y, Goldinfeld G, Haddad Y, Sgayer I, Lavinsky M, Lowenstein L, Frank Wolf M. Papaverine prior to catheter balloon insertion for labor induction: a randomized controlled trial. Am J Obstet Gynecol MFM. 2024 Jul;6(7):101388. doi: 10.1016/j.ajogmf.2024.101388. Epub 2024 May 31.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2025
• Primary Completion (Estimated): April 21, 2027
• Study Completion (Estimated): April 21, 2027

Study Registration Dates

• First Submitted: September 7, 2026
• First Submitted That Met QC Criteria: September 14, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Oxytocin; Papaverine; Labor induction; Premature rupture of membranes; Term PROM
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Fetal Membranes, Premature Rupture; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Inorganic Chemicals; Chlorine Compounds; Opiate Alkaloids; Sodium Compounds; Isoquinolines; Chlorides; Hydrochloric Acid; Benzylisoquinolines; Papaverine; Sodium Chloride
• Other Study ID Numbers: WOMC-0047-25

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