Clinical trial NCT04747301: DOuble-BAlloon Versus PROstaglandin E2 for Cervical Ripening in Low Risk Pregnancies
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Induction of Labor
Keywords: Induction of labor
Low-risk pregnancies
Double-balloon catheter
Prostaglandin E2
Lead sponsor: Hanoi Obstetrics and Gynecology Hospital
Sponsor class: OTHER
Collaborators: name: Mỹ Đức Hospital
First posted: 2021-02-10
Enrollment: 540
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants delivered vaginally
timeFrame: From randomization until delivery, assessed up to 3 days after randomization
Secondary outcomes:
measure: Number of participants with Side - effect of induction's method
timeFrame: From induction until delivery, assessed up to 3 days after induction
measure: Number of participants using more than one induction agent required
timeFrame: From induction until delivery, assessed up to 3 days after induction
measure: Number of participants having oxytocin augmentation
timeFrame: From induction until delivery, assessed up to 3 days after induction
measure: Number of participants with uterine tachysystole
timeFrame: From induction until delivery, assessed up to 3 days after induction
measure: Time from induction of labor to delivery
timeFrame: From induction until delivery, assessed up to 3 days after induction
measure: Number of participants delivered vaginally within 24 hours
timeFrame: Within 24 hours from labor induction
measure: Number of participants with post-partum haemorrhage
timeFrame: Within 24 hours from delivery
measure: Number of participants having uterine atony
timeFrame: From delivery until maternal hospital discharge, assessed up to 28 days after delivery
measure: Number of participants having maternal post-partum blood transfusion
timeFrame: From delivery until maternal hospital discharge, assessed up to 28 days after delivery
measure: Number of participants with hypertension complications
timeFrame: From randomization until maternal hospital discharge, assessed up to 28 days after randomization
measure: Number of participants with uterine dehiscence or rupture
timeFrame: From delivery until maternal hospital discharge, assessed up to 28 days after delivery
measure: Number of participants with maternal infection
timeFrame: From induction until maternal hospital discharge, assessed up to 28 days after induction
measure: Number of participants with hysterectomy
timeFrame: From delivery until maternal hospital discharge, assessed up to 28 days after delivery
measure: Number of participants with damage to internal organs
timeFrame: From delivery until maternal hospital discharge, assessed up to 28 days after delivery
measure: Number of participants with other post-partum complications
timeFrame: From randomization until maternal hospital discharge, assessed up to 28 days after randomization
measure: Number of participants admitted to intensive care unit
timeFrame: From randomization until maternal hospital discharge, assessed up to 28 days after randomization
measure: Number of maternal death among participants
timeFrame: From randomization until maternal hospital discharge, assessed up to 28 days after randomization
measure: Number of participants referred to other hospital due to severe morbidities
timeFrame: From randomization until maternal hospital referral, assessed up to 28 days after randomization
measure: Maternal length of stay
timeFrame: From admission until maternal hospital discharge, assessed up to 28 days after admission
measure: Psychometric aspects
timeFrame: At admission (version A) and before maternal hospital discharge (version B), assessed up to 28 days after admission
measure: Apgar scores at 1 and 5 minute
timeFrame: Assessed at 1 and 5 minute after birth
measure: Number of Infants with Apgar Score ≤7 at 1 and 5 minutes
timeFrame: Assessed at 1 and 5 minute after birth
measure: Number of neonates admitted to the Neonatal Intensive Care Unit or Intermediate care unit
timeFrame: From delivery until admission to Neonatal Intensive Care Unit or Intermediate care unit, assessed up to 7 days after delivery
measure: Reason for Neonatal Intensive Care Unit admission
timeFrame: From delivery until Neonatal Intensive Care Unit admission, assessed up to 28 days after delivery
measure: Length of stay at the Neonatal Intensive Care Unit or Intermediate care unit
timeFrame: 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
measure: Number of neonates with birth trauma
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with hypoglycemia
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with jaundice and hyperbilirubinemia
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with Hypoxic ischemic encephalopathy or need for therapeutic hypothermia
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with meconium aspiration syndrome
timeFrame: From delivery until neonatal hospital discharge, assessed up to 07 days after delivery
measure: Number of neonates in need for respiratory supports
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with neonatal infection
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with neonatal seizures
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates with intracranial hemorrhage
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates need blood transfusion
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonatal deaths
timeFrame: From delivery until neonatal hospital discharge, assessed up to 28 days after delivery
measure: Number of neonates referred to other hospital for severe morbidities
timeFrame: From delivery until neonatal hospital referral, assessed up to 28 days after delivery
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: Hanoi Obstetrics and Gynecology Hospital
state: Hà Nội
Study officials:
affiliation: Monash University
name: Ben W Mol, PhD. MD
role: STUDY_CHAIR
affiliation: Hanoi Obstetric and Gynecology Hospital
name: Anh Nguyen Duy, PhD. MD
role: STUDY_DIRECTOR
affiliation: Mỹ Đức Hospital
name: Vinh Dang Quang, PhD. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hanoi Obstetrics and Gynecology Hospital
name: Ha Nguyen Thi Thu, PhD. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.