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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Induction of Labor, Pain, Acute, Labor Pain, Delivery Delayed

Intervention / Treatment
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* Drug: IV Papaverine 80 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded randomized placebo controlled trial Group 1: will get IV PAPAVERINE 80 mg in 100 ml saline Group 2: will get IV 100 ml saline
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction of labor, Ripenning of the cervix, Catheter balloon, Antispasmodic