Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04201665 |
| Other study ID # |
0120-398/2019/7 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 13, 2020 |
| Est. completion date |
January 31, 2022 |
Study information
| Verified date |
June 2022 |
| Source |
University Medical Centre Ljubljana |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Studies found conflicting results on efficacy of uterotonic agents used to prevent and treat
uterine atony, the most common cause of postpartum hemorrhage. Uterine EMG can be used to
objectively assess myometrial contractility and, consequently, efficacy of different
uterotonics.
The investigators are planning a single-center, randomized, open-label trial to compare
uterine EMG parameters in women receiving oxytocin vs. those receiving carbetocin after
cesarean delivery.
Description:
RATIONALE
Postpartum hemorrhage is the leading cause of maternal mortality worldwide. In the Western
world the estimated risk of life threatening postpartum hemorrhage is 2 on 1000 births. Most
frequently (up to 90% of cases of postpartum hemorrhage) it is a consequence of uterine atony
or inappropriate uterine contraction. In clinical practice preventing postpartum hemorrhage
is key and routinely, different prophylactic uterotonic drugs are used. The first-line
recommended drug for postpartum hemorrhage prevention is oxytocin. However, a recent Cochrane
meta-analysis concluded that the most effective drugs (compared to oxytocin) to prevent
postpartum hemorrhage of 500 ml or more are ergometrine with oxytocin, misoprostol with
oxytocin and carbetocin.
Carbetocin is a synthetic heat-stable analogue of oxytocin, with a longer half-life. It
shares the same mechanism of action and the same side-effects as oxytocin. The recommended
dose of carbetocin is 100 μg, which is equivalent to 10 μg (5 IU) of oxytocin. In the WHO
carbetocin multicenter, double-blind, randomized trial, the intramuscular administration of
100 μg of heat-stable carbetocin was discovered to be noninferior to the administration of 10
IU of oxytocin for the prevention of postpartum hemorrhage after vaginal birth. Some studies
have found carbetocin to be an effective prophylactic agent with a favourable side effect
profile for the third stage of labour in caesarean sections, reducing the use of additional
uterotonic agents, blood and recovery time. Moreover, carbetocin was found to be effective in
reducing the need for additional uterotonic use and postpartum blood transfusion in women at
increased risk of postpartum hemorrhage undergoing cesarean delivery. In one study,
carbetocin was also found to be more effective than oxytocin in preventing postpartum
hemorrhage in twin pregnancies delivered by cesarean section.
Uterine contractions in pregnancy, labour and postpartum can be detected using
electromyography. Myometrial contractility can be objectively and non-invasively assessed in
vivo by monitoring uterine electromyography (EMG), as uterine contractions are the result of
the electrical activity generated and propagated in the myometrium.
To our knowledge, no study has reported oxytocin or carbetocin effects using postpartum
electromyography.
OBJECTIVE The objective of the study is to compare efficacy and objectively quantify the
effect of carbetocin (Pabal ®) with electromyography compared to the standard uterotonic
oxytocin (Syntocinon ®) for postpartum hemorrhage prevention.
METHODS Single-center, randomized, open-label trial.
After signed informed consent, the cesarean section will be performed. All the patients will
receive 5 IU of oxytocin bolus and a single oxytocin infusion (10 IU). Subsequently patients
will be transferred to high dependency unit and allocated randomly into one of two groups:
1. Carbetocin group Patients will receive a single dose of carbetocin 100 mcg (Pabal ®). An
electromyogram of the uterus will be performed and a blood sample will be obtained.
After 2-3 hours another electromyogram will follow, as well as a visual and quantified
estimation of blood loss.
2. Oxytocin group Patients will receive 5 IU of oxytocin (Syntocinon ®) as a 250 ml 0.9%
NaCl infusion. An electromyogram of the uterus will be performed and a blood sample will
be obtained. After 2-3 hours another electromyogram will follow, as well as a visual and
quantified estimation of blood loss.
Another blood sample will be routinely obtained 24 hours after the caesarean section.
Statistical analysis
From previous EMG studies, there has been reported difference in means of EMG PS peak
frequency in labor vs. non-labor patients of (0.56 - 0.44 = 0.12 Hz), and a standard
deviation of 0.15 Hz. Using power of 0.80, and an α - 0.05, with t-test, gives a desired
sample size of 26 per group minimum.
All data will be analyzed according to a pre-established statistical plan. Statistical
analyses will be performed with SPSS software (version 24.0; IBM Corporation, Armonk, New
York).
Data will be entered as numerical or categorical, as appropriate. Shapiro-Wilk test will be
used to assess normality of distribution. Parametric statistics will be carried out for
normally distributed variables; for non-normal distribution, nonparametric statistics will be
used. Data with normal distribution will be described using minimum, maximum and mean with
standard deviation. Data with non-normal distribution will be shown using minimum, maximum,
median, and interquartile range (IQR). Comparisons will be carried out between the study
groups using independent Student's t test or Mann-Whitney U test for continuous and with
Chi-square test for categorical variables.
