Intravenous Papaverine for Term Prelabor Rupture of Membranes

NCT07826533 | Recruiting

• 1 other identifier: WOMC-0047-25
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Premature Rupture of Fetal Membranes

Keywords

Term PROM; Premature rupture of membranes; Papaverine; Labor induction; Oxytocin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Mode of Delivery

  From rupture of membranes until delivery, assessed up to 48 hours

• Maternal Infectious Complications

  From rupture of membranes until delivery, assessed up to 48 hours

• Postpartum Hemorrhage

  From rupture of membranes until delivery, assessed up to 48 hours

• Apgar Score at 5 Minutes

  5 minutes after birth

• Umbilical Cord pH Below 7.1

  At birth, based on umbilical artery cord blood sampling

Study Arms (2)

Papaverine

EXPERIMENTAL

Participants received intravenous papaverine 80 mg diluted in 100 mL of 0.9% normal saline.

Drug: Papaverine

Placebo

PLACEBO COMPARATOR

Participants received 100 mL of intravenous 0.9% normal saline as placebo.

Drug: Normal Saline Placebo Infusion

Interventions

Papaverine DRUG

Papaverine 80 mg diluted in 100 mL of 0.9% normal saline, administered intravenously as a single study infusion.

Papaverine

Normal Saline Placebo Infusion DRUG

100 mL of 0.9% normal saline, administered intravenously as a single placebo study infusion.

Also known as: 0.9% Sodium Chloride

Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wolfson Medical Center: lead

Study Sites (1)

The Edith Wolfson Medical Center

Holon, 5822012, Israel

RECRUITING

Related Publications (5)

• Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.

  PMID: 32080050 BACKGROUND

• 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.

  PMID: 28050900 BACKGROUND

• 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.

  PMID: 38825005 BACKGROUND

• 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.

  PMID: 14698825 BACKGROUND

• 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.

  PMID: 23737030 BACKGROUND

MeSH Terms

Conditions

Fetal Membranes, Premature Rupture

Interventions

Papaverine; Sodium Chloride

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Opiate Alkaloids; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Eliel Kedar Sade, MD

CONTACT

+972-52-6008068; elielbob@gmaill.com

Ornit Cohen

CONTACT

+972-3-5028399; ornitc@wmc.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Treatment allocation was known only to one study team member who prepared the study infusions according to the randomization list. Participants, treating clinicians, investigators, and personnel involved in outcome assessment remained blinded to treatment allocation. Study infusions were prepared in identical 100-mL normal saline bags and were labeled without revealing group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants were randomized in a 1:1 ratio to receive intravenous papaverine or placebo in two parallel groups.

Study Record Dates

• First Submitted: September 7, 2026
• First Posted: September 17, 2026
• Study Start: March 20, 2025
• Primary Completion (Estimated): April 21, 2027
• Study Completion (Estimated): April 21, 2027
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)