The Effect of IV PAPAVERINE 80 mg Prior to Catheter Balloon Insertion on Bishop Score and Pain

The Effect of IV PAPAVERINE 80 mg Prior to Catheter Balloon Insertion on Bishop Score and Pain, Double Blinded Randomized Placebo Controlled Trial

The cervix consists of connective tissue, smooth muscle, and parasympathetic innervation. Smooth muscle makes up about 15% of the cervix, is mainly found under the internal opening of the neck. Papaverine and its derivatives are musculotropic antispasmodic drugs that directly affect smooth muscle, the mechanism is to reduce the spasm of smooth muscle resulting in relaxation. Studies on the pharmacokinetics of this drug show that it has a half-life of 0.5-2 hours and its effect is apparent within 10 minutes.

Administration of antispasmodic drugs during childbirth is common in developing and developed countries. Based on previous studies, the use of these drugs during childbirth may lead to a faster opening of the cervix. Possible uses of Papaverine include, administered separately or in combination with other treatments such as rupture of amniotic membranes and/or Oxytocin administration. According to some studies, administration of Papaverine at birth can be used as a preventive or therapeutic strategy in cases of prolonged labor or first stage over 12 hours as defined in some studies. According to Kochran et al, who included 13 experiments with 1995 participants, the use of antispasmodic drugs shortened the first stage of labor by an average of 74.34 minutes. In 6 experiments that included 820 patients, the administration of antispasmodic drugs during labor increases the rate of cervical opening by an average of 0.61 cm per hour.

In addition to the muscle relaxation effect, studies have been published on the analgesic effect of PAPAVERINE for example in patients with urinary stones.

In the present study, the investigators want to test the effect of administering PAPAVERINE IV 80 mg within half an hour before the insertion of a catheter balloon for cervical ripening on the Bishop score after catheter removal between the two groups.

Study Overview

• Status: Recruiting
• Conditions: Labor Pain; Pain, Acute; Induction of Labor; Delivery Delayed
• Intervention / Treatment: Drug: Placebo; Drug: IV Papaverine 80 mg

Detailed Description

There are different methods of induction of labor, the choice of the best method for that patient depends on the bishop score, an estimate that is based on data related to the cervix such as opening, effacement and other parameters, also the choice of the method of induction depends on the obstetric history of the patient. A Bishop score less than 6 indicates an unriped cervix, therefore increasing the chance of labor induction failure,methods have been developed to ripen the cervix; among the methods are catheter balloon insertion and prostaglandins. The mechanisms by which the catheter works include a mechanical effect and indirect effect on local secretion of prostaglandins.

The cervix consists of connective tissue, smooth muscle, and parasympathetic innervation. Smooth muscle makes up about 15% of the cervix, is mainly found under the internal opening of the neck. Papaverine and its derivatives are musculotropic antispasmodic drugs that directly affect smooth muscle, the mechanism is to reduce the spasm of smooth muscle resulting in relaxation. Studies on the pharmacokinetics of this drug show that it has a half-life of 0.5-2 hours and its effect is apparent within 10 minutes.

Administration of antispasmodic drugs during childbirth is common in developing and developed countries. Based on previous studies, the use of these drugs during childbirth may lead to a faster opening of the cervix. Possible uses of Papaverine include, administered separately or in combination with other treatments such as rupture of amniotic membranes and/or Oxytocin administration. According to some studies, administration of Papaverine at birth can be used as a preventive or therapeutic strategy in cases of prolonged labor or first stage over 12 hours as defined in some studies. According to Kochran et al, who included 13 experiments with 1995 participants, the use of antispasmodic drugs shortened the first stage of labor by an average of 74.34 minutes. In 6 experiments that included 820 patients, the administration of antispasmodic drugs during labor increases the rate of cervical opening by an average of 0.61 cm per hour.

In addition to the muscle relaxation effect, studies have been published on the analgesic effect of PAPAVERINE for example in patients with urinary stones.

In the present study, the investigators want to test the effect of administering PAPAVERINE IV 80 mg within half an hour before the insertion of a catheter balloon for cervical ripening on the Bishop score after catheter removal between the two groups.

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raneen Abu Shqara, MD; Phone Number: +972549793591; Email: rabushqara@gmail.com
• Study Contact Backup: Name: Maya Frank Wolf, MD; Phone Number: +972507887800; Email: mayaw@gmc.gov.il

Study Locations

• Israel
  • Hazafon
    • Nahariya, Hazafon, Israel
      • Recruiting
      • Galilee Medical Center
      • Contact: Amal Shahen; Email: amals@gmc.gov.il

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women with a singleton pregnancy, over the age of 18, pregnant at term (ie between weeks 37-42)
• Bishop score is less than 6, for which a medical decision was made regarding the induction of labor by catheter
• Vertex presentation, intact membranes
• Viable fetus

Exclusion Criteria:

• Twin pregnancy
• Women after caesarean section
• Severe fetal anomalies
• Women with vaginismus or vulvodynia
• Women with psychiatric illnesses including depression and schizophrenia
• Contraindication for vaginal delivery
• A woman who is unable to sign a consent form
• Women are known for supraventricular tachycardia
• Women with tachycardia over 100 or arrhythmia
• Known sensitivity to one of the components of the drug
• Liver disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention group- IV PAPAVERINE 80 mg; Administration of IV PAPAVERINE 80 mg in 100 ml of saline, once within half an hour before inserting a single-balloon balloon catheter	Drug: IV Papaverine 80 mg; Opium alkaloid antispasmodic drug; Other Names: Papaverine Hydrochloride
Placebo Comparator: Conrol group- Placebo group.; Administration of 100 ml of saline within half an hour before the insertion of a single-balloon catheter	Drug: Placebo; Placebo; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The delta Bishop score	The difference between the bishop score (a score of the cervix ripening) before and after the insertion of Foley catheter. Higher delta Bishop scores means better outcome	1 year
Pain during insertion of the catheter	Pain during insertion of the catheter based on visual scale analoug (0-10) score, . The minimum is 0, the maximum is 10. Higher score means worse outcome	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction-delivery interval	Time from insertion of the catheter balloon to delivery. Longer interval means worse outcome	2 years
Success	Bishop score (a score of cervix ripenining) after extraction of the catheter above or equal to 8. Bishop score above or equal to 8, means better outcome	2 years
Use of other ripening method	The need for other ripening method due to low bishop score (<6) after extraction of the catheter balloon	2 years
Insertion-extraction of the catheter interval	Time between insertion to extraction of the catheter balloon.	2 years
Delivery method	Cesarean or vaginal delivery	2 years
Maternal satisfaction	Based on visual scale analoug score for satisfaction (1-5), the minimum is 1, the maximum is 5, higher score means better outcome	1 year
Apgar Score	The Apgar score, is a score given to the newborn in 1,5 and 10 minutes after birth, and is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth.	2 years
Cord pH	Cord blood gas analysis is an objective measure of the fetal metabolic condition at the time of delivery	2 years
Need for neonatal intensive case admission	Is a measure of neonatal complications at birth	2 years

Collaborators and Investigators

• Sponsor: Western Galilee Hospital-Nahariya
• Investigators: Principal Investigator: Maya Frank Wolf, MD, Galilee Medical Center

Publications and helpful links

General Publications

• Rohwer AC, Khondowe O, Young T. Antispasmodics for labour. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD009243. doi: 10.1002/14651858.CD009243.pub2.
• 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.
• Ibrahim MI, Alzeeniny HA, Ellaithy MI, Salama AH, Abdellatif MA. Drotaverine to improve progression of labor among nulliparous women. Int J Gynaecol Obstet. 2014 Feb;124(2):112-7. doi: 10.1016/j.ijgo.2013.08.013. Epub 2013 Nov 7.
• Madhu C, Mahavarkar S, Bhave S. A randomised controlled study comparing Drotaverine hydrochloride and Valethamate bromide in the augmentation of labour. Arch Gynecol Obstet. 2010 Jul;282(1):11-5. doi: 10.1007/s00404-009-1188-8. Epub 2009 Jul 31.
• Snir N, Moskovitz B, Nativ O, Margel D, Sandovski U, Sulkes J, Livne PM, Lifshitz DA. Papaverine hydrochloride for the treatment of renal colic: an old drug revisited. A prospective, randomized study. J Urol. 2008 Apr;179(4):1411-4. doi: 10.1016/j.juro.2007.11.053. Epub 2008 Mar 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: March 5, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Induction of labor; Antispasmodic; Ripenning of the cervix; Catheter balloon
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Labor Pain; Acute Pain; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Papaverine
• Other Study ID Numbers: 0012-23-NHR

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