Comparison of Pre-Induction Cervical Ripening

Study Overview
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Brief Summary
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This study is designed to assess the effectiveness of a combination method of induction of labor using a urinary balloon catheter and prostaglandin gel. The vaginal delivery rate for medical induction of labor is lower than the vaginal delivery rate for spontaneous labor. As a consequence, the frequency of cesarean section for failed induction in the United States is rising. This has led to a renewed effort to examine the effectiveness of the varied methods of induction. The study is a randomized, unblinded trial of urinary balloon catheter and prostaglandin gel for induction of labor in term pregnant patients. Pregnant women presenting to the Palmetto Health Richland for a scheduled induction of labor will be offered enrollment in the trial. Patients who enroll in the study will be randomized into one of 3 study arms: urinary balloon catheter only, prostaglandin gel only and combination urinary balloon catheter and prostaglandin gel. Randomization will be per sealed envelope from the locked nurse medication storage area (Pyxis) located in Labor and Delivery at Palmetto Health Richland. The investigator will be given the next sequentially numbered study randomization envelope by the patient's nurse. The randomization assignment will be unblinded to the patient and her physicians. If the patient is not in active labor 6 hours after initiation of the intervention, a standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician.

Detailed Description
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Title: Comparison of pre-induction cervical ripening using Prepidil gel administered through a urinary balloon catheter Precis- This study is designed to assess the effectiveness of a combination method of induction of labor using a urinary balloon catheter and prostaglandin gel. Background Induction of labor is a common intervention during pregnancy1. The frequency of hospital admissions for induction of labor is increasing in the United States. Indications for induction of labor include maternal disease, fetal complications and social/geographical issues. Obstetricians may also choose elective induction, to facilitate delivery at term for the physician or patient who does not have a medical indication for delivery. The vaginal delivery rate for medical induction of labor is lower than the vaginal delivery rate for spontaneous labor. As a consequence, the frequency of cesarean section for failed induction in the United States is rising2. This has led to a renewed effort to examine the effectiveness of the varied methods of induction3-5. The vaginal delivery rate for induction of labor can be predicted by assessing the patient's cervical examination prior to induction. The Bishop Score uses the cervical examination components to predict the vaginal delivery rate for a particular patient. A low or poor Bishop score predicts a low success rate for vaginal delivery. There are 3 common methods used to induce labor. The first are physiological methods such as breaking the patient's water or causing contractions by nipple stimulation. Breaking the patient's water requires a high (favorable) Bishop Score and cannot be safely performed with a low (poor) Bishop score. This method has a higher success rate in patients who have had a prior vaginal delivery. Nipple stimulation has been associated with an increased risk of tachysystole (too frequent contractions) and non-reassuring fetal heart rate patterns. It is not considered an acceptable method of induction in the United States. Physical methods include pre-induction cervical ripening with laminaria or urinary balloon catheter6. Both of these methods are designed to force the cervix to open mechanically. Laminaria are small sticks of dehydrated seaweed which are placed in the cervical canal. As the sticks hydrate, the cervical canal dilates. Balloon urinary catheters are inserted into the cervical canal. The balloon is inflated in the lower uterine segment. A weight is placed on the catheter to apply traction which forces the fluid-filled balloon to dilate the cervical canal. Urinary balloon catheters have been used alone7,8, with saline infusion9-11 or with prostaglandin infusion12-16. Pharmacological methods include ergot alkaloids, prostaglandin E and F series and oxytocin. Ergot alkaloids cause forceful uterine contractions and have been used to treat postpartum hemorrhage. Ergot alkaloids may cause severe hypertension during induction of labor and are not used in the United States. Prostaglandin E and F series cause increased uterine muscle tone (tonic contractions). They are used for pre-induction cervical ripening. The different prostaglandins have varying complications which may include nausea, vomiting, diarrhea and fever. Use of misoprostol for pre-induction cervical ripening has been associated with an increased risk of uterine rupture both in normal patients and in patients who have had previous cesarean sections17. The method of drug delivery for prostaglandin medications has varied. It can be administered as an oral tablet, a vaginal suppository, a vaginal gel, or by infusion into the lower uterine segment via a urinary balloon catheter. It is unclear, based on evidence-based medicine, whether any particular method of delivery is superior to another. The Food and Drug Administration of the United States (FDA) has approved the use of Prepidil gel (prostaglandin E2) for pre-induction cervical ripening18,19. Prepidil gel is administered as a gel into the vaginal fornix using a syringe. Oxytocin is a pituitary hormone which can be used to augment spontaneous labor or to induce labor. It results in both increased uterine tone (tonic contractions) and increased contraction frequency (clonic contractions). It is considered the most physiologic method of pre-induction cervical ripening. Oxytocin is administered by intravenous infusion. Methods of induction can be used individually or in combination. The most common combination method for induction of labor is the use of prostaglandin for pre-induction cervical ripening followed by oxytocin. Objectives- The current study is a randomized, unblinded trial of urinary balloon catheter and prostaglandin gel for induction of labor in term pregnant patients. The primary outcome to be studied is vaginal delivery rate for urinary balloon catheter alone, prostaglandin gel alone and a combination of urinary balloon catheter and prostaglandin gel. Secondary outcomes to be studied include the safety of the method, composite maternal morbidity and composite neonatal morbidity. The null hypothesis is that there is no difference in the vaginal delivery rate between the three study protocols. Study Design and Methods- Pregnant women presenting to the Palmetto Health Richland for a scheduled induction of labor will be offered enrollment in the trial. Eligible patients will undergo an interview with the investigator. Enrollment pre-requisites and exclusions will be reviewed with the patient. The patient will also be provided with written information regarding the safety of prepidil as an pre-induction cervical ripening agent and the safety of urinary balloon catheters as a pre-induction cervical ripening agent. The investigator will review general information on the trial and an informed consent. Patients who decline enrollment in the trial will have the method of pre-induction cervical ripening chosen by their physician. Inclusion Criteria: Single, live fetus Cephalic (head-first) presentation Reassuring fetal health assessment Gestational age between 26 and 42 weeks Maternal age 18 and above Bishop score less than 5 Exclusion Criteria: Multiple Gestation (twins, triplets, quadruplets) Fetal demise Fetal malpresentation Estimated fetal weight less than 500 grams or more than 4000 grams Placenta previa Non-reassuring fetal health assessment Maternal asthma Latex allergy Spontaneous labor Other contraindication to vaginal delivery Patients who enroll in the study will be randomized into 3 study arms: urinary balloon catheter only, prostaglandin gel only and combination urinary balloon catheter and prostaglandin gel. Randomization will be made by choosing a sealed envelope from the locked nurse medication storage area (Pyxis) located on Labor and Delivery at Palmetto Health Richland. Randomization will be 1:1:1 with randomization envelopes prepared by statisticians at the University of South Carolina Arnold School of Public Health. The investigator will be given the next sequentially numbered study envelope by the patient's nurse. The randomization included will be unblinded to the patient and her physicians. URINARY BALLLOON CATHETER ONLY ARM The patient will be placed in the lithotomy position, either in the bed or in stirrups. A baseline digital exam of the cervix will be performed by the physician and a Bishop score recorded. A urinary balloon catheter will be placed through the cervix into the lower uterine segment, either digitally or with the aid of a speculum. Once the catheter is properly positioned, the bulb will be inflated with 40ml of normal saline. The urinary balloon catheter will then be secured to the patient's thigh using tape. The catheter will then be placed under traction by attaching it to a liter bag of saline. The catheter will be deflated and removed after 6 hours, with the time of removal recorded in the medical record. If the catheter is spontaneously expelled from the uterus, the time of expulsion will be noted by the nurse. Six (6) hours after insertion of the catheter, the physician will perform a digital cervical exam and a Bishop score recorded. If the patient is not in active labor at the time of catheter removal or expulsion, a standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician. Artificial rupture of membranes may also be carried out at the physician's discretion. PREPIDIL ONLY ARM The patient will be placed in the lithotomy position, either in the bed or in stirrups. A baseline digital exam of the cervix will be performed by the physician and a Bishop score recorded in the medical record. Prepidil gel will be inserted into the vaginal fornix according to the manufacturer's direction. No oxytocin or other intervention will commence until 6 hours after insertion of the gel. Six (6) hours after insertion of the gel, the physician will perform a digital cervical exam and a Bishop score recorded. If the patient is not in active labor 6 hours after the administration of Prepidil gel, a standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician. Artificial rupture of membranes may also be carried out at the physician's discretion. COMBINED URINARY BALLOON CATHETER AND PREPIDIL GEL ARM The patient will be placed in the lithotomy position, either in the bed or in stirrups. A baseline digital exam of the cervix will be performed by the physician and a Bishop score recorded. A urinary balloon catheter will be placed through the cervix into the lower uterine segment, either digitally or with the aid of a speculum. Once the catheter is properly positioned, the bulb will be inflated with 40ml of normal saline. The urinary balloon catheter will then be secured to the patient's thigh using tape. The catheter will then be placed under traction by attaching it to a liter bag of saline. Prepidil gel will be inserted through the urinary balloon catheter into the lower uterine segment, in a dose equivalent to the manufacturer's recommendation. No oxytocin or other intervention will commence until 6 hours after insertion of the catheter and prepidil gel (even if the catheter is spontaneously expelled prior to that time). Six (6) hours after insertion of the catheter and gel, the physician will perform a digital cervical exam and a Bishop score recorded. The catheter will be deflated and removed after 6 hours, with the time of removal noted by the nurse. If the catheter is spontaneously expelled from the uterus, the time of expulsion will be noted by the nurse. If the patient is not in active labor 6 hours after insertion of prepidil gel, a standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician. Artificial rupture of membranes may also be carried out at the physician's discretion.

Official Title
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Comparison of Pre-Induction Cervical Ripening Using Prepidil Gel Administered Through a Urinary Balloon Catheter.

Conditions
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Failed Labour

Intervention / Treatment
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* Drug: Prepidil Gel
* Device: Urinary Balloon Catheter
* Other: Combined Urinary Catheter & Prepidil Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single, live fetus Cephalic (head-first) presentation Reassuring fetal health assessment Gestational age between 26 and 42 weeks Maternal age 18 and above Bishop score less than 5 Exclusion Criteria: Multiple Gestation (twins, triplets, quadruplets) Fetal demise Fetal malpresentation Estimated fetal weight less than 500 grams or more than 4000 grams Placenta previa Non-reassuring fetal health assessment Maternal asthma Latex allergy Spontaneous labor Other contraindication to vaginal delivery

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Urinary Balloon Catheter Only<br>A urinary balloon catheter will be placed through the cervix into the lower uterine segment and the bulb inflated with 40ml of saline. The catheter will be taped to the patient's thigh and placed under traction using a liter bag of saline. The catheter will be deflated and removed after 6 hours. If spontaneously expelled from the uterus, time of expulsion will be noted. Six hours after insertion of catheter, a digital exam will be performed and Bishop score recorded. If no active labor at time of catheter removal or expulsion, standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician. | Device: Urinary Balloon Catheter<br>* Pre-induction cervical ripening using a urinary balloon catheter device.<br>* Other names: Foley Catheter;|
| Active Comparator: Prepadil Only<br>Prepidil Only : Prepidil gel will be inserted into the vaginal fornix according to manufacturer's direction. No oxytocin or other intervention will commence until 6 hours after insertion of gel. Six hours after insertion of gel, digital exam will be performed and Bishop score recorded. If no active labor 6 hours after the administration of gel, standardized protocol of oxytocin will commence. Labor management will be at the discretion of the physician. | Drug: Prepidil Gel<br>* Pre-induction cervical ripening using dinoprostone gel in the vagina.<br>|
| Experimental: Combined Urinary Catheter & Prepidil Gel<br>A urinary balloon catheter will be placed through the cervix into the lower uterine segment and the bulb inflated with 40ml of saline. The catheter will be taped to the patient's thigh and placed under traction using a liter bag of saline. Prepidil gel will be inserted through the catheter into the lower uterine segment, in a dose equivalent to manufacturer's recommendation. No oxytocin or other intervention will commence until 6 hours after insertion of the catheter and administration of prepidil gel (even if catheter is spontaneously expelled). After 6 hours, digital exam will be performed and Bishop score recorded. If no active labor, standardized protocol of oxytocin will commence. | Other: Combined Urinary Catheter & Prepidil Gel<br>* Pre-induction cervical ripening using dinoprostone gel injected through a urinary balloon catheter placed in the lower uterine segment.<br>* Other names: Prepidil Gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal Delivery | The primary outcome of this study is vaginal delivery of a liveborn singleton pregnancy. The outcome is considered a vaginal delivery if accomplished by spontaneous vaginal delivery, operative forceps or vacuum forceps. The alternate outcome is delivery by cesarean section. | Gestational age 26-42 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Labor, obstetric, Labor, induced