DOuble-BAlloon Versus PROstaglandin E2 for Cervical Ripening in Low Risk Pregnancies (DOBA-PRO)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Induction of Labor
• Intervention / Treatment: Device: Double-balloon catheter (UTAH CVX-RIPE) for cervical ripening; Drug: Dinoprostone 10mg (Propess)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 540
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ha Nguyen Thi Thu, PhD. MD; Phone Number: 0084989661093; Email: thuha.ivf@gmail.com
• Study Contact Backup: Name: Toan Nguyen Khac, MSc. MD; Phone Number: 0084948387988; Email: ngkhactoan@gmail.com

Study Locations

• Vietnam
  • Hà Nội
    • Hanoi, Hà Nội, Vietnam, 10000
      • Recruiting
      • Hanoi Obstetrics and Gynecology Hospital
      • Contact: Ha Thu Thi Nguyen, MD.PhD; Phone Number: 0084989661093; Email: thuha.ivf@gmail.com
      • Contact: Toan Nguyen Khac, MD.MSc; Phone Number: 0084948387988; Email: ngkhactoan@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Maternal age ≥ 18
2. Singleton pregnancy. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks gestational age.
3. Gestational age at randomization from at 39+0 to 40+6 weeks of gestation.
4. Cephalic presentation
5. Intact membrane
6. Unfavourable cervix (Bishop<6)
7. Informed consent

Exclusion Criteria:

1. 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.)
2. Abnormal placenta: Active vaginal bleeding greater than bloody show or placenta previa, accreta or vasa previa

3. Abnormal amniotic fluid volume:

   • Oligohydramnios (MVP < 2cm)
   • Polyhydramnios (MVP > 10cm)

4. 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)
5. Previous C-section
6. Planned for C-section or contra-indication to labour
7. Cerclage or use of pessary in current pregnancy
8. Refusal of blood product.
9. Participation in another interventional study that influences management of labour at delivery or perinatal morbidity or mortality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Double-balloon catheter group; 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; 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.
Other: Vaginal insertion Prostaglandin E2 group; 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); 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.; Other Names: Vaginal Prostaglandin E2 (Propess)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hanoi Obstetrics and Gynecology Hospital
• Collaborators: Mỹ Đức Hospital
• Investigators: Principal Investigator: Vinh Dang Quang, PhD. MD, Mỹ Đức Hospital; Principal Investigator: Ha Nguyen Thi Thu, PhD. MD, Hanoi Obstetrics and Gynecology Hospital; Study Chair: Ben W Mol, PhD. MD, Monash University; Study Director: Anh Nguyen Duy, PhD. MD, Hanoi Obstetric and Gynecology Hospital

Publications and helpful links

General Publications

• Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, Hill K, Thom EA, El-Sayed YY, Perez-Delboy A, Rouse DJ, Saade GR, Boggess KA, Chauhan SP, Iams JD, Chien EK, Casey BM, Gibbs RS, Srinivas SK, Swamy GK, Simhan HN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. N Engl J Med. 2018 Aug 9;379(6):513-523. doi: 10.1056/NEJMoa1800566.
• Cromi A, Ghezzi F, Uccella S, Agosti M, Serati M, Marchitelli G, Bolis P. A randomized trial of preinduction cervical ripening: dinoprostone vaginal insert versus double-balloon catheter. Am J Obstet Gynecol. 2012 Aug;207(2):125.e1-7. doi: 10.1016/j.ajog.2012.05.020. Epub 2012 Jun 1.
• Suffecool K, Rosenn BM, Kam S, Mushi J, Foroutan J, Herrera K. Labor induction in nulliparous women with an unfavorable cervix: double balloon catheter versus dinoprostone. J Perinat Med. 2014 Mar;42(2):213-8. doi: 10.1515/jpm-2013-0152.
• de Vaan MD, Ten Eikelder ML, Jozwiak M, Palmer KR, Davies-Tuck M, Bloemenkamp KW, Mol BWJ, Boulvain M. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019 Oct 18;10(10):CD001233. doi: 10.1002/14651858.CD001233.pub3.
• Dos Santos F, Drymiotou S, Antequera Martin A, Mol BW, Gale C, Devane D, Van't Hooft J, Johnson MJ, Hogg M, Thangaratinam S. Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study. BJOG. 2018 Dec;125(13):1673-1680. doi: 10.1111/1471-0528.15397. Epub 2018 Sep 10.
• Du YM, Zhu LY, Cui LN, Jin BH, Ou JL. Double-balloon catheter versus prostaglandin E2 for cervical ripening and labour induction: a systematic review and meta-analysis of randomised controlled trials. BJOG. 2017 May;124(6):891-899. doi: 10.1111/1471-0528.14256. Epub 2016 Aug 17.
• Liu YR, Pu CX, Wang XY, Wang XY. Double-balloon catheter versus dinoprostone insert for labour induction: a meta-analysis. Arch Gynecol Obstet. 2019 Jan;299(1):7-12. doi: 10.1007/s00404-018-4929-8. Epub 2018 Oct 12.
• Shechter-Maor G, Haran G, Sadeh-Mestechkin D, Ganor-Paz Y, Fejgin MD, Biron-Shental T. Intra-vaginal prostaglandin E2 versus double-balloon catheter for labor induction in term oligohydramnios. J Perinatol. 2015 Feb;35(2):95-8. doi: 10.1038/jp.2014.173. Epub 2014 Oct 2.
• Du C, Liu Y, Liu Y, Ding H, Zhang R, Tan J. Double-balloon catheter vs. dinoprostone vaginal insert for induction of labor with an unfavorable cervix. Arch Gynecol Obstet. 2015 Jun;291(6):1221-7. doi: 10.1007/s00404-014-3547-3. Epub 2014 Nov 19.
• Wang W, Zheng J, Fu J, Zhang X, Ma Q, Yu S, Li M, Hou L. Which is the safer method of labor induction for oligohydramnios women? Transcervical double balloon catheter or dinoprostone vaginal insert. J Matern Fetal Neonatal Med. 2014 Nov;27(17):1805-8. doi: 10.3109/14767058.2014.880880. Epub 2014 Feb 3.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 22, 2021
• First Submitted That Met QC Criteria: February 5, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Induction of labor; Low-risk pregnancies; Double-balloon catheter; Prostaglandin E2
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Dinoprostone
• Other Study ID Numbers: PSHN.0001.2021

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