Papaverine for Prevention of Perineal Trauma

The Impact of Intrapartum Papaverine 80 mg on Perineal Trauma Among Primiparous Women: a Prospective Randomized Double-blind Study.

Perineal trauma is a common complication of vaginal delivery, particularly among primiparous patients, and may result in short- and long-term maternal morbidity, including pain, dyspareunia, and pelvic floor dysfunction. Papaverine hydrochloride, a smooth muscle relaxant with vasodilatory properties, has been shown to improve tissue relaxation and has been used safely in obstetric settings.

This prospective randomized double-blind placebo-controlled study aims to evaluate whether intrapartum intravenous papaverine hydrochloride (80 mg), administered at full cervical dilatation, reduces the rate of perineal trauma among primiparous patients undergoing vaginal delivery. Eligible participants will be randomized in a 1:1 ratio to receive either intravenous papaverine hydrochloride or placebo (normal saline). Maternal, obstetric, and neonatal outcomes, including the rate and severity of perineal trauma, obstetric anal sphincter injuries (OASIS), postpartum hemorrhage, and neonatal outcomes, will be assessed.

Study Overview

• Status: Not yet recruiting
• Conditions: Obstetric Anal Sphincter Injury; Perineal Trauma
• Intervention / Treatment: Drug: Papaverine Hydrochloride; Drug: Placebo

Detailed Description

Perineal trauma is a frequent complication of vaginal birth and is particularly common among primiparous patients. Rates of second-degree perineal tears among nulliparous women have been reported to range between 35% and 78%, while obstetric anal sphincter injuries (OASIS) occur in approximately 0.7% to 2% of vaginal deliveries. Perineal trauma may result in substantial maternal morbidity, including postpartum pain, dyspareunia, pelvic floor dysfunction, urinary or anal incontinence, and impaired quality of life.

Several intrapartum interventions have been investigated to improve perineal tissue elasticity and reduce birth-related trauma, including warm perineal compresses, perineal massage, and active perineal protection techniques. However, pharmacological approaches aimed at enhancing tissue relaxation during labor remain poorly studied.

Papaverine hydrochloride is a smooth muscle relaxant with vasodilatory properties that acts directly on smooth muscle fibers. In obstetric settings, papaverine has been associated with improved cervical ripening and shorter labor duration without significant maternal or neonatal adverse effects. Due to its pharmacological effects on tissue relaxation and vascular perfusion, papaverine may potentially reduce resistance of the perineal tissues during childbirth and consequently decrease the rate and severity of perineal trauma.

Retrospective data from the investigators' institution, including 4,939 primiparous patients, demonstrated lower rates of first- and second-degree perineal tears among women who received intrapartum papaverine. However, because of the retrospective nature of these findings, causal conclusions cannot be established, and prospective randomized evaluation is warranted.

The objective of the present study is to determine whether intravenous papaverine hydrochloride (80 mg), administered at full cervical dilatation, reduces the rate of perineal trauma among primiparous patients undergoing vaginal delivery.

This study is designed as a prospective, randomized, double-blind, placebo-controlled trial. Eligible participants will be randomized in a 1:1 ratio to receive either intravenous papaverine hydrochloride (80 mg diluted in 100 mL normal saline) or placebo (100 mL normal saline) following complete cervical dilatation. Participants, treating physicians, and outcome assessors will remain blinded to treatment allocation.

The primary outcome will be the rate of perineal trauma requiring suturing following vaginal delivery. Secondary outcomes will include the rate of OASIS, episiotomy, mode of delivery, postpartum hemorrhage, manual placental removal, maternal adverse effects, and neonatal outcomes including birthweight, 5-minute Apgar score, umbilical cord pH, and neonatal intensive care unit admission

• Study Type: Interventional
• Enrollment (Estimated): 412
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Primiparous patients aged 18 years or older
• Singleton pregnancy
• Term pregnancy (37+0 to 42+0 weeks of gestation)
• Cephalic presentation
• Undergoing labor with at least with 2 cm cervical dilatation.
• Ability to provide written informed consent

Exclusion Criteria:

• Multiple gestation
• Major fetal congenital anomalies
• Contraindication to vaginal delivery
• Known hypersensitivity or allergy to papaverine hydrochloride
• Known supraventricular tachycardia (SVT)
• Maternal tachycardia (heart rate >100 bpm) or clinically significant cardiac arrhythmia
• Known liver disease or hepatic dysfunction
• Active psychiatric condition impairing the ability to provide informed consent
• Inability to provide written informed consent
• Planned cesarean delivery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Papaverine Group; Participants randomized to this arm will receive intravenous papaverine hydrochloride 80 mg diluted in 100 mL normal saline administered at full cervical dilatation during labor.	Drug: Papaverine Hydrochloride; Intravenous papaverine hydrochloride 80 mg diluted in 100 mL normal saline administered at full cervical dilatation during labor. The study medication will be administered following complete cervical dilatation and prior to delivery in primiparous patients undergoing vaginal birth.
Placebo Comparator: Placebo Group; Participants randomized to this arm will receive placebo consisting of 100 mL normal saline administered intravenously at full cervical dilatation during labor.	Drug: Placebo; Placebo consisting of 100 mL normal saline administered intravenously at full cervical dilatation during labor. The placebo solution will be prepared in an identical manner to maintain blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Perineal Trauma Requiring Suturing	The rate of perineal trauma requiring suturing following vaginal delivery, including first-, second-, third-, and fourth-degree perineal tears.	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Obstetric Anal Sphincter Injuries (OASIS)	Rate of third- and fourth-degree perineal tears diagnosed following vaginal delivery.	1 day
Rate of Episiotomy	Rate of mediolateral episiotomy performed during delivery.	1 day
Mode of Delivery	Mode of delivery including spontaneous vaginal delivery, operative vaginal delivery, or cesarean delivery.	1 day
Postpartum Hemorrhage (PPH)	Rate of postpartum hemorrhage diagnosed following delivery according to institutional criteria.	1 day
Manual Placental Removal	Need for manual placental removal following delivery.	1 day
Maternal Hemoglobin Drop	Difference between pre-delivery hemoglobin level and the lowest postpartum hemoglobin level measured during hospitalization.	1 day
Maternal Adverse Events	Maternal adverse effects including tachycardia, hypotension, nausea, vomiting, headache, and dry mouth following study drug administration.	7 days
Neonatal Outcomes	5-Minute Apgar Score	1 day
NICU Admission	Need for neonatal intensive care unit admission following birth.	7 days

Collaborators and Investigators

• Sponsor: Dr Raneen Abu Shqara

Study record dates

Study Major Dates

• Study Start (Estimated): June 3, 2026
• Primary Completion (Estimated): June 3, 2027
• Study Completion (Estimated): June 3, 2027

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 6, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Labor; Vaginal Delivery; Papaverine; Perineal Trauma
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Opiate Alkaloids; Isoquinolines; Benzylisoquinolines; Papaverine
• Other Study ID Numbers: 0015-26-NHR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be made publicly available due to participant privacy considerations and institutional data protection policies. De-identified data may be available from the principal investigator upon reasonable request and subject to institutional review and approval.

Drug and device information, study documents

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