|Methods||Randomised trial, two-arm, individual randomisation stratified as either nulliparous or multiparous. Analysed by both intention-to-treat, and as-treated for selected outcomes.|
|Participants||Setting: Single facility in Dallas County, USA.|
Period of data collection: December 2008 - January 2011.
Inclusion criteria: Women with spontaneous labour that reached the active phase of labour (defined as cervical dilation of 4 cm or more) but did not progress, maternal age 16 years or older, gestational age 36 weeks or more, singleton, cephalic presentation, reassuring FHR, cervical dilation between 4 and 8 cm, and English or Spanish speaking. Eligible individuals were required to have ruptured membranes with an intrauterine pressure catheter in place confirming the presence of fewer than 200 Montevideo units of uterine activity, the absence of tachysystole, defined as 6 or more contractions in a single 10-min period, and the absence of uterine hypertonus, defined as a single contraction lasting longer than 120 seconds.
Exclusion criteria: non-reassuring FHR pattern, meconium-stained amniotic fluid, previous uterine incision, maternal fever (defined as temperature 38°C or higher), known fetal anomalies, placenta previa or unexplained vaginal bleeding, estimated fetal weight 4500 g or more, abnormal bony pelvis, and parity of 6 or more.
Participants: 439 women met inclusion criteria, of which 350 (79.7%) consented and were randomised. Women recruited were mostly Hispanic (88% Hispanic, 5% White, 7% African American).
|Interventions||Experimental group: 75 mcg of oral misoprostol, for up to 2 doses 4 hrs apart. This was prepared by cutting generic 100 mcg misoprostol tablets into one-half and one-quarter tablets. Women were eligible for a second dose of misoprostol if they had a reassuring FHR tracing and did not experience uterine tachysystole or hypertonus after the first dose. All women in the misoprostol arm were assessed for drug failure 2 hrs after administration of the second dose. If they experienced less than 200 Montevideo units and minimal cervical change, IV oxytocin was initiated. If women randomised to the misoprostol arm developed a non-reassuring fetal heart rate (defined as tachycardia, prolonged or late decelerations, moderate to severe variable decelerations (nadir of up to 90 beats per min for more than 30 seconds or a duration of 60 seconds or longer), or any combination of these), uterine tachysystole, or hypertonus before the administration of misoprostol, the study drug was withheld and labour augmented with IV oxytocin.|
176 (50.3%) women were randomised to the experimental group, of which 136 (77.30%) received the study drug and 40 (22.7%) did not.
Control group: Women received titrated IV oxytocin according to a hospital protocol of a 6 milliunits/min starting dose, followed by incremental increases of 6 milliunits/min at 40-min intervals, up to a maximum dose of 42 milliunits/min. The protocol also specified use of 3-milliunit/min or 1-milliunit/min doses if tachysystole or hypertonus were encountered. The oxytocin was prepared as a 20 units/L solution in isotonic saline and administered by using calibrated infusion pumps.
174 (49.7%) randomised to the control group, of which 143 (82.2%) women received the control drug and 31 (17.8%) did not.
|Outcomes||Primary outcome: incidence of uterine tachysystole, hypertonus, or both in a 10-min period.|
Uterine tachysystole in a 20-min interval (defined as 6 contractions in 2 consecutive 10-min periods).
Apgar score less than 4 at 5 mins of life.
Umbilical cord artery pH less than 7.1.
Admission to the NICU.
Chorioamnionitis (defined as a temperature of 38°C or higher in the absence of other sources of infection).
Maternal blood transfusion for hypovolaemia.
Mode of delivery elapsed time from start of labour augmentation to complete cervical dilatation.
Elapsed time from the start of labour augmentation to delivery.
Maximum number of Montevideo units.
Diagnosis of non-reassuring FHR were evaluated.
Also reported on other outcomes:
Tachystole in a 10-min period.
Hypertonus in a 10-min period.
Tachysystole, hypertonus, or both associated with non-reassuring FHR.
Caesarean for dystocia.
Caesarean for non-reassuring FHR.
Time from admission to study drug (min).
Duration of second stage (min).
Maximum oxytocin doses (milliunits/min).
|Notes||Several continuous outcomes were reported as median (interquartile range) rather than mean (standard deviation).|
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Random sequence generation (selection bias)||Low risk||Computer-generated randomisation sequence.|
|Allocation concealment (selection bias)||Low risk||On enrolment, an opaque envelope corresponding to the participant’s enrolment number was opened.|
|Blinding of participants and personnel (performance bias) |
|Unclear risk||Women and care staff were not blinded to treatment allocation once it has been assigned, suggesting a high risk of bias. However, it is unclear what (if any) effect this may have had on most outcomes, but the risk of bias is likely to be high for the epidural analgesia outcome.|
|Blinding of outcome assessment (detection bias) |
|Unclear risk||Outcome assessors were blinded for judgements of FHR traces and uterine hyperstimulation - low risk of bias for these outcomes only. However, outcome assessment was not blinded for other outcomes but it is unclear what (if any) effect this may have had.|
|Incomplete outcome data (attrition bias) |
|Unclear risk||20.3% of study participants overall (22.7% in experimental group and 17.8% in control group) did not receive study drugs - reasons were reported, however the authors did not explain why the proportion attributable to progression to 8 cm prior to initiation of augmentation differed between groups (18/40 women in experimental group and 30/31 in control group). It is also unclear how many women randomised to misoprostol arm eventually received oxytocin due to drug failure, as per study protocol.|
|Selective reporting (reporting bias)||Unclear risk||The study reported on 5 additional secondary outcomes (uterine tachysystole in a 20-min interval, birthweight, elapsed time from the start of labour augmentation to delivery, maximum number of Montevideo units, diagnosis of non-reassuring FHR) compared to the outcomes stated in the clinical trial protocol registration, and did not report on one of the stated clinical trial protocol outcomes (maternal metritis). The reason for these changes was not stated and it is unclear what effect this may have had on conclusions.|
|Other bias||Unclear risk||20% of women declined participation when approached; the reason for this is unclear.|