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.