DOuble-BAlloon Versus PROstaglandin E2 for Cervical Ripening in Low Risk Pregnancies

Study Overview
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Brief Summary
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To compare the effectiveness and safety of double balloon catheter and vaginal insert Prostaglandin E2 in cervical ripening prior to Induction of Labor in low-risk women from 39+0 to 40+6 weeks of gestation.

Detailed Description
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Induction of labor (IOL) is a technique to establish vaginal delivery when the risks for continuing the pregnancy for mother or baby are higher than the risks of delivery. In case the cervix is unripe, cervical ripening before the onset of labor is needed. The two main mechanisms of cervical ripening can be categorized as mechanical or pharmacological. A Cochrane systematic review and other recent meta-analysis have shown that cervical ripening with a balloon is probably as effective as induction of labor with vaginal Prostaglandin E2. However, this conclusion is based on low to moderate quality evidence. Only a limited number of randomized clinical trials (RCTs) have been conducted. Many of those suffering from small sample sizes and different study subjects, i.e. high-risk subjects only, and mixed population. In current practice, induction of labor is not only used in high-risk patients with clear indications for pregnancy termination. The ARRIVE trial has shown a significant benefit of labor induction over expectant management among the low-risk population. Based on this evidence, the American College of Obstetricians and Gynecologists (ACOG) has suggested: It's time to induce of labor at 39th week of gestation. Since then, there is a trend in favoring elective induction before the due date over expectant management. Besides, more and more pregnant women want to shorten the duration of pregnancy or to time the birth of the baby due to the convenience of the mother and/or healthcare workers. This makes the optimal method of Induction of Labor in terms of effectiveness and safety for both mothers and their babies even more important. In this study, the investigators will compare the effectiveness and safety of double-balloon catheter and Prostaglandin E2 for elective labor induction in low-risk pregnancies.

Official Title
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The Effectiveness and Safety of Double-balloon Versus Vaginal Prostaglandin for Cervical Ripening in Women With Low-risk Pregnancies: A Randomized Controlled Trial (DOBA-PRO)

Conditions
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Induction of Labor

Intervention / Treatment
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* Device: Double-balloon catheter (UTAH CVX-RIPE) for cervical ripening
* Drug: Dinoprostone 10mg (Propess)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal age ≥ 18 Singleton pregnancy. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks gestational age. Gestational age at randomization from at 39+0 to 40+6 weeks of gestation. Cephalic presentation Intact membrane Unfavourable cervix (Bishop<6) Informed consent Exclusion Criteria: Maternal medical illness associated with increased risk of adverse pregnancy outcome (any diabetes mellitus, any hypertensive disorders, cardiac diseases, renal insufficiency, systemic lupus erythematosus, mental disorders, HIV positive, use of heparin or low-molecular weight heparin during the current pregnancy etc.) Abnormal placenta: Active vaginal bleeding greater than bloody show or placenta previa, accreta or vasa previa Abnormal amniotic fluid volume: Oligohydramnios (MVP < 2cm) Polyhydramnios (MVP > 10cm) Abnormal fetus Fetal demise or known major fetal anomalies Fetal growth restriction (FGR) (EFW < 3% or < 10% and abnormal Doppler) Non-reassuring fetal status (no fetal movements, abnormal fetal heart rate at auscultation) Previous C-section Planned for C-section or contra-indication to labour Cerclage or use of pessary in current pregnancy Refusal of blood product. Participation in another interventional study that influences management of labour at delivery or perinatal morbidity or mortality

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
Interventional Model Description: Low-risk pregnant women eligible for study will be asked to sign the informed consent form. Then, they will be randomly assigned in a 1:1 ratio to receive either double balloon insertion or vaginal prostaglandin E2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Double-balloon catheter group<br>Sweeping the membranes by UTAH CVX-RIPE® (Utah Medical Products, Inc, 7043 South 300 West, Midvale, Utah 84047 USA). | Device: Double-balloon catheter (UTAH CVX-RIPE) for cervical ripening<br>* Sweeping the membranes by UTAH CVX-RIPE® (Utah Medical Products, Inc, 7043 South 300 West, Midvale, Utah 84047 USA). The catheter will be inserted manually until the proximal balloon is in the cervical canal, the distal balloon should be intrauterine and in the extra-amniotic space. The intrauterine balloon is inflated with 40mL saline and retracted so that it rests against the internal oz. The proximal balloon should now be outside the external oz and is inflated with 20mL saline. If the balloons are correctly situated on both ends of the cervix, they can be inflated with up to 80mL saline each. Cardiotocograph will be performed 30min, 2 hours after insertion and every 6 hours. The balloon is placed for a maximum of 24 hours. If it is expelled in the first 12 hours and the patient has no contractions or still shows an unfavorable cervix, another balloon is placed for a maximum of another 24 hours. The patients will be examined in case of extremely painful or membranes ruptured.<br>|
| Other: Vaginal insertion Prostaglandin E2 group<br>Propess® 10mg Vaginal delivery system (Ferring Controlled Therapeutics Ltd., 1 Redwood Place, Peel Park Campus, East Kilbride, Glasgow, G74 5PB, UK) is a vaginal insert containing 10mg of dinoprostone in a timed-release formulation (the medication is released at 0.3 mg/hour). | Drug: Dinoprostone 10mg (Propess)<br>* Propess® 10mg Vaginal delivery system (Ferring Controlled Therapeutics Ltd., 1 Redwood Place, Peel Park Campus, East Kilbride, Glasgow, G74 5PB, UK) is a vaginal insert containing 10mg of dinoprostone in a timed-release formulation (the medication is released at 0.3 mg/hour). A Propess vaginal system is inserted by a research doctors. As in the catheter procedure, Fetal Heart Rate is monitored 30min before and 2 hours after placement. Cardiotocograph and vaginal examination will be performed every 6 hours. The vaginal system is placed for a maximum of 24 hours. If it is expelled in the first 12 hours and the patient has no contractions or still shows an unfavorable cervix, another vaginal system is placed for a maximum of another 24 hours. The patients will be examined in case of extreme pain or membranes ruptured.<br>* Other names: Vaginal Prostaglandin E2 (Propess);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants delivered vaginally | Number of participants delivered vaginally | From randomization until delivery, assessed up to 3 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Side - effect of induction's method | Including any of: nausea, vomiting, diarrhea, pain... | From induction until delivery, assessed up to 3 days after induction | 
| Number of participants using more than one induction agent required | Number of participants using more than one induction agent required | From induction until delivery, assessed up to 3 days after induction | 
| Number of participants having oxytocin augmentation | Number of participants having oxytocin augmentation | From induction until delivery, assessed up to 3 days after induction | 
| Number of participants with uterine tachysystole | Defined as more than 5 contractions in 10 minutes over a minimal period of two times 10 minutes with Fetal Heart Rate changes and/or a contraction lasting more than 3 minutes with Fetal Heart Rate changes. | From induction until delivery, assessed up to 3 days after induction | 
| Time from induction of labor to delivery | Duration from induction to delivery (hours) | From induction until delivery, assessed up to 3 days after induction | 
| Number of participants delivered vaginally within 24 hours | Number of participants delivered vaginally within 24 hours | Within 24 hours from labor induction | 
| Number of participants with post-partum haemorrhage | Defined as blood loss >500 ml at vaginal birth or >1000 ml at caesarean birth within 24 hours after birth | Within 24 hours from delivery | 
| Number of participants having uterine atony | Use of two or more uterotonics other than oxytocin; other surgical interventions such as uterine compression by hands and/or sutures, uterine artery ligation, embolization, hypogastric ligation, or balloon tamponade). | From delivery until maternal hospital discharge, assessed up to 28 days after delivery | 
| Number of participants having maternal post-partum blood transfusion | Number of participants having maternal post-partum blood transfusion | From delivery until maternal hospital discharge, assessed up to 28 days after delivery | 
| Number of participants with hypertension complications | Number of participants with hypertension complications | From randomization until maternal hospital discharge, assessed up to 28 days after randomization | 
| Number of participants with uterine dehiscence or rupture | Uterine dehiscence (defined as clinically asymptomatic disruption of the uterus that is discovered incidentally at surgery) or rupture (defined as clinically significant rupture involving the full thickness of the uterine wall and requiring surgical repair) | From delivery until maternal hospital discharge, assessed up to 28 days after delivery | 
| Number of participants with maternal infection | Fever (defined as a temperature ≥37.5 degrees Celsius) Start of intravenous broad-spectrum antibiotics (with evidence of infection confirmed by clinical and subclinical presentation) Endometritis, myometritis or urinary tract infection (proven positive vaginal discharge/urine culture) | From induction until maternal hospital discharge, assessed up to 28 days after induction | 
| Number of participants with hysterectomy | Hysterectomy for any postpartum complications | From delivery until maternal hospital discharge, assessed up to 28 days after delivery | 
| Number of participants with damage to internal organs | Including intestines, bladder or ureters | From delivery until maternal hospital discharge, assessed up to 28 days after delivery | 
| Number of participants with other post-partum complications | Includes: venous embolism, pulmonary embolism, stroke, cardiac arrest | From randomization until maternal hospital discharge, assessed up to 28 days after randomization | 
| Number of participants admitted to intensive care unit | Number of participants admitted to intensive care unit | From randomization until maternal hospital discharge, assessed up to 28 days after randomization | 
| Number of maternal death among participants | Maternal death from randomization through hospital discharge | From randomization until maternal hospital discharge, assessed up to 28 days after randomization | 
| Number of participants referred to other hospital due to severe morbidities | Including: pulmonary embolus, stroke, cardiorespiratory arrest, etc. | From randomization until maternal hospital referral, assessed up to 28 days after randomization | 
| Maternal length of stay | Duration of stay in hospital (days) | From admission until maternal hospital discharge, assessed up to 28 days after admission | 
| Psychometric aspects | Feelings and thoughts pregnant women at antepartum and postpartum will be evaluated by Wijma Delivery Expectancy/Experience Questionnaires' (W-DEQ) version A and version B, respectively, expected to be filled out in approximately 30 minutes This is a questionnaire which measures a construct of fear related to childbirth during pregnancy and after delivery by asking the woman about her expectancies before delivery(version A) - performed at admission, and experiences after delivery (version B) - performed before maternal hospital discharge respectively. When filling in the W-DEQ, the woman is instructed to rate her personal feelings and cognitions on a six-point scale. The minimum score is 0 and the maximum score is 126. The higher the score, the greater the fear of childbirth manifested. | At admission (version A) and before maternal hospital discharge (version B), assessed up to 28 days after admission | 
| Apgar scores at 1 and 5 minute | Apgar scores at 1 and 5 minute | Assessed at 1 and 5 minute after birth | 
| Number of Infants with Apgar Score ≤7 at 1 and 5 minutes | Infants with Apgar Score ≤7 at 1 and 5 minutes | Assessed at 1 and 5 minute after birth | 
| Number of neonates admitted to the Neonatal Intensive Care Unit or Intermediate care unit | Number of neonates admitted to the Neonatal Intensive Care Unit or Intermediate care unit | From delivery until admission to Neonatal Intensive Care Unit or Intermediate care unit, assessed up to 7 days after delivery | 
| Reason for Neonatal Intensive Care Unit admission | Reason for Neonatal Intensive Care Unit admission such as: respiratory distress, hypoglycemia, seizures, etc. | From delivery until Neonatal Intensive Care Unit admission, assessed up to 28 days after delivery | 
| Length of stay at the Neonatal Intensive Care Unit or Intermediate care unit | Duration from admission to Neonatal Intensive Care Unit or Intermediate care unit to Neonatal Intensive Care Unit/ Intermediate care unit discharge or hospital referral | From admission to Neonatal Intensive Care Unit/ Intermediate care unit until neonatal discharge or hospital referral, assessed up to 28 days after Neonatal Intensive Care Unit admission | 
| Number of neonates with birth trauma | Include: bone fractures, traumatic pneumothorax, facial nerve palsy, other neurologic injury (Brachial plexus palsy...), etc. | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with hypoglycemia | Number of neonates with hypoglycemia | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with jaundice and hyperbilirubinemia | Number of neonates with jaundice and hyperbilirubinemia | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with Hypoxic ischemic encephalopathy or need for therapeutic hypothermia | Number of neonates with Hypoxic ischemic encephalopathy or need for therapeutic hypothermia | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with meconium aspiration syndrome | Criteria include: Meconium-stained amniotic fluid Respiratory distress at birth or shortly after birth Characteristic radiographic features: The initial chest film may show streaky, linear densities -> the lungs typically appear hyper-inflated with flattening of the diaphragms. | From delivery until neonatal hospital discharge, assessed up to 07 days after delivery | 
| Number of neonates in need for respiratory supports | Incubation, Continuous Positive Airway Pressure, or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation within the first 72 hours | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with neonatal infection | Presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid (CSF), or catheterized/supra-pubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an X-ray confirming infection | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with neonatal seizures | Number of neonates with neonatal seizures | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates with intracranial hemorrhage | Intra-ventricular hemorrhage grades III and IV, subgaleal hematoma, subdural hematoma, or subarachnoid hematoma Subgaleal hematoma, subdural hematoma, or subarachnoid hematoma | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates need blood transfusion | Number of neonates need blood transfusion | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonatal deaths | Includes: Intrapartum/neonatal/perinatal deaths | From delivery until neonatal hospital discharge, assessed up to 28 days after delivery | 
| Number of neonates referred to other hospital for severe morbidities | Number of neonates referred to other hospital for severe morbidities | From delivery until neonatal hospital referral, assessed up to 28 days after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction of labor, Low-risk pregnancies, Double-balloon catheter, Prostaglandin E2