Methods
This is a prospective cohort randomized controlled study conducted at the KK Women’s and Children’s Hospital (KKH) and University Malaya Medical Center (UMMC), teritary hospitals each with an approximate 11000 deliveries annually. The study was conducted from January 2015 to January 2018. Local institutional review board approval was achieved in both centers. 210 women were recruited in each center. ClinicalTrials.gov Identifier: NCT02620215. Funding for the study was supported by SingHealth Duke-NUS OBGYN Academic Clinical Program (ACP) Grant.
The main hypothesis is DBC has no major adverse events including hyperstimulation and non-reassuring fetal status in a 12-hour period after DBC insertion, and its efficacy is non-inferior to prostaglandin insertion. This will allow it to fulfil a current void in offering safer outpatient induction. We attempt to address this hypothesis by monitoring the periods of regular uterine contractions (>1:10) measuring the frequency, length of contractions and its association with adverse events during this period after intervention. We also examined the efficiency of DBC in achieving a favourable cervix for rupture of membranes or active labour at the end of 12 hours compared with PGE2.
NICE guidelines on induction of labour [9] defined uterine hyperstimulation as contractions more than 5 in 10 min for more than 20 min or contractions lasting more than 2 min in duration. A retrospective study involving prostaglandin induction of labour[10] showed that hyperstimulation occurred in 5.8% of cases. Arbitrarily, we considered a relative 80% decrease in hyperstimulation risk (estimated hyperstimulation with DBC 1%) as clinically significant. Hence, assuming a significance level of 5% and power of 80%, and allowing for a 5% dropout rate, we estimated that 210 subjects would be needed per group (one-sided test).
Randomization of the women is achieved with third party sealed envelope allocation. 210 envelopes containing DBC allocation and another 210 identical envelopes containing prostaglandin pessary allocation were prepared by a third party. The 420 envelopes were shuffled according to a computer randomization code after sealing and labelled with a randomization allocation number from 1 to 420. Half of the envelopes were handed to the each center’s principal investigator, and kept in the clinical store on labour ward together with the stock of DBC and prostaglandin pessary.
Women requiring term IOL were identified in both centers and screened with the inclusion and exclusion criteria (Box 1. Inclusion and exclusion criteria). Once the written informed consent was obtained a research assistant would disclose the intervention allocation.
In the group allocated the DBC, the catheter was inserted into the cervical canal either under direct visualization with a sterile speculum examination or via vaginal examination. After both balloons have entered the cervical canal, the uterine balloon was filled with 40 ml of saline, the catheter was then retracted and a vaginal examination was done to ensure the DBC is in the cervical canal and the vaginal balloon was inflated to 40 ml of saline. Both balloons were then inflated to 80 ml each. The tubing was then taped to the woman’s thigh. After the DBC was put in place, a cardiotocogram was performed for 60 to 120 minutes and the woman was allowed to ambulate. The double balloon catheter was left in place for a maximum of 12 hours as per the manufacturer’s advice. Failed induction of labour was defined when labour was not initiated after removal of the DBC.
In the group allocated the vaginal prostaglandin pessary, the pessary was inserted and placed in the posterior vaginal fornix. After insertion of the pessary, a cardiotocogram was performed for 60 to 120 min and the woman was allowed to ambulate. After 6 hours, if the woman is not in labour and the bishop score was still less than 6, a second dose of prostaglandin was inserted and monitored as previously described. Failed induction of labour was defined when labour was not initiated after insertion of 2 pessaries.
The women were continuously monitored for uterine activity and non-reassuring fetal status. During the first 12 hours of the intervention, women were monitored for hyperstimulation defined when there was more than 5 contractions for 10 min and hypertonus defined as a single contraction lasting for more than 2 minutes. The type of pain relief use was recorded (entonox, intramuscular pethidine or epidural). Any vaginal bleeding that was more than a “show” was recorded. Features of any non-reassuring heart rate was recorded and this was defined in accordance to the NICE intrapartum care guidelines.[11] Decisions for caesarean section based on cardiotocographs were made by obstetrician consultants on labour ward.
After the DBC was removed or expelled, and if vaginal examination revealed that the cervical os was more than 3 cm, membranes were ruptured and oxytocin infusion was started for women who were not in labour. For the prostaglandin group, during a vaginal examination, if the cervical os was more than 3 cm, membranes were ruptured and oxytocin infusion started 6 hours after the last dose of prostaglandin. Oxytocin was administered using a standard regime in each hospital. Once in active labour, standardized intrapartum care was given according to hospital protocol.
All decisions for caesarean sections were made by obstetrician consultants on labour ward. Failure to progress in first stage of labour was defined as the absence of cervical change for 4 hours or more in the presence of adequate uterine contractions and cervical dilation of at least 4 cm. During second stage of labour women who were undelivered with no progress with active pushing after at least 2 hours in multiparous women and 3 hours in nulliparous women were diagnosed as failure to progress.
Statistical analysis of outcomes data was performed with Chi squared test and R software.