Misoprostol administered sublingually at a dose of 12.5 ?g versus vaginally at a dose of 25 ?g for the induction of full-term labor: a randomized controlled trial protocol.
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ABSTRACT: Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-?g misoprostol administered sublingually compared to a 25-?g vaginal dose of the drug for the induction of labor.A triple-blind, multicenter, placebo-controlled, randomized clinical trial will be conducted in Brazil at the Instituto de Medicina Integral Prof. Fernando Figueira and at the Assis Chateaubriand Maternity Teaching Hospital of the Federal University of Ceará. A total of 140 patients with full-term pregnancies, a live fetus, a Bishop score???6 and a recommendation of induction of labor will be randomized to one of two groups. One group will receive 12.5-?g sublingual tablets of misoprostol and placebo vaginal tablets, while the other group will receive placebo sublingual tablets and vaginal tablets containing 25 ?g of misoprostol. The principal endpoint is the rate of tachysystole. The secondary endpoints are vaginal delivery within 24 h of induction, uterine hyperstimulation, Cesarean section, severe neonatal morbidity or perinatal death, severe maternal morbidity or maternal death, and maternal preference regarding the route of administration of the drug. Student's t-test, and the chi-square test of association or Fisher's exact test, as appropriate, will be used in the data analysis. Risk ratios and their respective 95% confidence intervals will be calculated.Misoprostol has been identified as a safe, inexpensive, easily administered option for the induction of labor, with satisfactory results. An experimental study has shown that misoprostol administered sublingually at a dose of 25 ?g appears to be effective and is associated with greater maternal satisfaction when labor is induced in women with an unfavorable cervix. Nevertheless, the rate of tachysystole remains high; therefore, further studies are required to determine the ideal dose and the ideal interval of time between doses.ClinicalTrial.gov, NCT01406392 .
Misoprostol administered sublingually at a dose of 12.5 μg versus vaginally at a dose of 25 μg for the induction of full-term labor: a randomized controlled trial protocol.
<h4>Background</h4>Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-μg misoprostol administered sublingually compared to a 25-μg vaginal dose of ...[more]
Project description:BackgroundLabor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 μg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 μg versus vaginally at a dose of 25 μg to induce labor in a full-term pregnancy with a live fetus.MethodsA randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 μg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 μg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated.ResultsThe frequency of tachysystole was lower in the group using 12.5 μg misoprostol sublingually compared to the group using 25 μg misoprostol vaginally (RR = 0.15; 95%CI: 0.02-0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant.ConclusionThe effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative.Trial registrationRegistration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.
Project description:OBJECTIVE:To compare effectiveness and safety of oral misoprostol (50 μg every four hours as needed), low dose vaginal misoprostol (25 to 50 μg every six hours as needed), and our established dinoprostone vaginal gel (one to two mg every six hours as needed) induction. MATERIALS AND METHODS:Consenting women with a live term single cephalic fetus for indicated labor induction were randomized (3N = 511). Prior uterine surgery or non-reassuring fetal surveillance were exclusions. Concealed computer generated randomization was stratified and blocked. Newborns were assessed by a team unaware of group assignment. The primary outcome was time from induction at randomization to vaginal birth for initial parametric analysis. Sample size was based on mean difference of 240 minutes with α2 = 0.05 and power 95%. Non-parametric analysis was also pre-specified ranking cesareans as longest vaginal births. RESULTS:Enrollment was from April 1999 to December 2000. Demographics were similar across groups. Analysis was by intent to treat, with no loss to follow up. Mean time (±SD) to vaginal birth was 1356 (±1033) minutes for oral misoprostol, 1530 (±3249) minutes for vaginal misoprostol, and 1208 (±613) minutes for vaginal dinoprostone (P = 0.46, ANOVA). Median times to vaginal birth were 1571, 1339, and 1451 minutes respectively (P = 0.46, Kruskal-Wallis). Vaginal births occurred within 24 hours in 44.9, 53.5 and 47.7% respectively (P = 0.27, χ2). There were no significant differences in Kaplan Meier survival analyses, cesareans, adverse effects, or maternal satisfaction. The newborn who met birth asphyxia criteria received vaginal misoprostol, as did. all three other newborns with cord artery pH<7.0 (P = 0.04, Fisher Exact). CONCLUSION:There was no significant difference in effectiveness of the three groups. Profound newborn acidemia, though infrequent, occurred only with low dose vaginal misoprostol.
Project description:The IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full-term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 μg followed by 50 μg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography-tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one-compartment nonlinear clearance model. The absorption rate constant (ka ) was dependent on both route and dose of administration: buccal 25 μg 0.724 (95% confidence interval, 0.54-0.92) h-1 ; 50 μg 0.531 (0.37-0.63) h-1 ; vaginal 25 μg 0.507 (0. 2-1. 4) h-1 ; and 50 μg 0.246 (0.103-0.453) h-1 . Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63-4.77). There was no effect of body mass index or age on apparent clearance 705 (431-1099) L/h or apparent volume of distribution 632 (343-1008) L. The area under the concentration-time curve to 4 h following the first 25 μg dose of misoprostol was 16.5 (15.4-17.5) pg h/ml for buccal and 34.3 (32.5-36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.
Project description:ObjectiveTo evaluate whether cervical ripening with oral misoprostol increases cesarean delivery risk and prolongs time to vaginal delivery compared with vaginal misoprostol in a predominantly overweight population.MethodsThis single center, retrospective cohort study was performed at a tertiary care academic medical center and compared labor induction outcomes with vaginal misoprostol to outcomes with oral misoprostol after a complete institutional shift to oral misoprostol. Labor induction using 25 micrograms vaginal misoprostol in 2013-2014 was compared with 50 micrograms oral misoprostol in 2014-2015. The primary outcome was cesarean delivery. Secondary outcomes included time to vaginal delivery, uterine tachysystole, maternal hemorrhage, and composite adverse neonatal outcomes. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios (aOR) as the measures of effect.ResultsThere were 138 women in the oral and 138 women in the vaginal misoprostol groups. In the overall cohort, the median (interquartile range) body mass index was 31.7 (28.2-36.8) and most women (72%) were of either black or Hispanic race or ethnicity. The frequency of cesarean delivery was higher in the oral than the vaginal misoprostol group (32% vs 21%; P=.04). The adjusted odds of cesarean was higher with oral misoprostol (aOR 2.01; 95% CI 1.07-3.76). Among nulliparous women, the frequency of cesarean delivery was 41% in the oral and 28% in the vaginal misoprostol groups (aOR 2.79; 95% CI 1.26-6.19). Women had a longer time to vaginal delivery in the oral compared with vaginal misoprostol group (41 vs 31 hours respectively, P=.01). Tachysystole occurred more frequently with vaginal misoprostol (20% vs 11%; P=.04).ConclusionCompared with vaginal misoprostol, oral misoprostol may be associated with increased risk of cesarean delivery and longer time to vaginal delivery.
Project description:BackgroundThe Induction of labor is the most common obstetric procedure in daily practice. Introducing propranolol as a new drug to augment the action of prostaglandins will help in the induction process and decrease CS rates. Several researchers have used propranolol in the augmentation of labor.AimThis pilot study compares propranolol and misoprostol versus misoprostol alone for labor induction in primigravids.MethodsThis is a Randomized clinical trial, single-blinded, placebo-controlled trial at Ain Shams University Maternity hospital. This study included 128 pregnant full-term primigravid women candidates for labor induction, randomized into two groups. All candidates underwent labor induction with 25 µg of vaginal misoprostol. Group I received 20 mg of oral propranolol tablets, while group II received sugary pills as a placebo. Candidates who responded successfully to induction were assessed for possible augmentation of labor by amniotomy or oxytocin infusion. The Primary outcome was induction to delivery interval, while the secondary outcomes were the duration of the latent phase, mode of delivery, and APGAR score of the neonate.ResultsThe induction-delivery time was (11.8 ± 8.1 h. vs. 12.6 ± 8.9 h., P value = 0.027) and the duration of the latent phase of labor (7.9 ± 5.6 h. vs. 9.2 ± 6.03 h., P value = 0.017) were significantly shorter in the group of misoprostol and propranolol compared to the group of misoprostol and placebo. There was no statistically significant difference between both groups' mode of delivery, indications for cesarean section, misoprostol, and oxytocin doses, or neonatal outcome. (P value > 0.05).ConclusionPropranolol, when used with misoprostol for induction of labor, results in augmentation of action of misoprostol and a significantly shorter induction-delivery interval.Trial registrationWe retrospectively registered this trial in clinicaltrial.gov on 01/09/2020 (NCT04533841). https://clinicaltrials.gov/ct2/show/NCT04533841.
Project description:BackgroundThe safest, most effective and fastest combined approaches to induction of labor is unknown. In an open-label randomized clinical trial we evaluated the efficacy of combination of extra-amniotic Foley's catheter and vaginal misoprostol compared to vaginal misoprostol alone for cervical ripening and induction of labor on the incidence of failed induction, induction-to-delivery interval and adverse maternal and perinatal outcomes.MethodsPregnant women at gestational age of 28 weeks or greater admitted at Kenyatta National Hospital, Kenya for induction of labor were enrolled then randomized to either a combination of extra-amniotic Foley's catheter inflated by 30 cm3 of normal saline and 25 micrograms of vaginal misoprostol or 25 micrograms of vaginal misoprostol alone. Women underwent 6 hourly reviews and additional misoprostol inserted if required. The primary outcome was incidence of failed induction. Secondary outcomes were induction-to-delivery interval and adverse maternal and perinatal outcomes. We conducted an intent-to-treat analysis and compared means or medians using t-test or Wilcoxon rank, proportions using Chi-square or Fishers test as appropriate. Induction-to-delivery interval were compared using the log-rank test. P-values of < 0.05 and 95% confidence intervals that excluded the null were considered statistically significant.ResultsBetween February and May 2016, we enrolled 180 of 237 pregnant women admitted for induction of labor and randomized them to either a combination of extra-amniotic Foley's catheter and vaginal misoprostol (n = 90) or vaginal misoprostol alone (n = 90). The socio-demographic and obstetric characteristics were similar between the two groups. Failed induction rates were lower but not statistically significant following combined extra-amniotic Foley's catheter and vaginal misoprostol (8.9%) versus vaginal misoprostol alone (11.1%). The mean induction-to-delivery time was 4.8 h shorter in the combined extra-amniotic Foley's catheter and vaginal misoprostol (mean 18.9, standard deviation (SD) 7.2 h) compared to misoprostol only group (mean 14.1, SD 6.9 h) (log-rank test, p < 0.001). Maternal and perinatal complications were similar between the two groups.ConclusionsExtra-amniotic Foley's catheter and vaginal misoprostol for cervical ripening and induction of labor did not significantly lower the incidence of failed induction but safely shortened induction-to-delivery time compared to vaginal misoprostol only.Trial registrationTrial was retrospectively registered on 14-03-2016 PACTR201604001535825.
Project description:ImportanceQuantification of potential consequences associated with the use of epidural analgesia during labor could help to improve the safety and quality of labor and delivery care for parturient women.ObjectiveTo evaluate the association between epidural analgesia use during labor and neonatal infection in a large cohort of parturient women.Design, setting, and participantsThis propensity score-matched cohort study was conducted at a university-affiliated hospital in Shanghai, China. Women at full-term pregnancy undergoing vaginal delivery between January 2013 and October 2018 were included in the study. Parturient women who were parous, experiencing premature delivery (gestational age <37 weeks), were pregnant with more than 1 fetus, or had experienced a stillbirth were excluded. Data were analyzed from October 2019 to June 2020.ExposuresThe use of epidural analgesia during labor.Main outcomes and measuresThe primary outcome was the incidence of neonatal infection, including neonatal sepsis, neonatal uncharacterized infection, neonatal pneumonia, and neonatal necrotizing enterocolitis reported in the medical record. Secondary outcomes included the incidence of maternal intrapartum fever and histologic chorioamnionitis.ResultsAmong 37 786 parturient women included (mean [SD] age, 29.5 [3.0] years), 19 968 (52.8%) received epidural analgesia during labor. In the propensity score-matched cohort (including 15 401 parturient women in each group), use of epidural analgesia was associated with a higher incidence of neonatal infection (absolute risk difference, 2.6%, 95% CI, 2.2%-3.0%; relative risk [RR], 2.43; 95% CI, 2.11-2.78), including higher incidence of sepsis (absolute risk difference, 0.1%, 95% CI, 0.1%-0.2%; RR, 3.50; 95% CI, 1.73-7.07) and uncharacterized infection (absolute risk difference, 2.2%, 95% CI, 1.9% to 2.6%; RR, 2.69; 95% CI, 2.30-3.15), compared with no epidural analgesia use. Use of epidural analgesia was also associated with greater incidence of maternal intrapartum fever (RR, 4.12; 95% CI, 3.78-4.50) and histologic chorioamnionitis (RR, 4.08; 95% CI, 3.59-4.64) compared with no epidural analgesia use.Conclusions and relevanceThis cohort study found that use of epidural analgesia in full-term nulliparous women undergoing vaginal delivery was associated with an increased risk of neonatal infection, pending further investigation. These findings support efforts to further improve safety and quality of labor and delivery care for parturient women.
Project description:BackgroundInduction of labor occurs in greater than 22% of all pregnancies in the United States. Previous studies have shown that misoprostol is more effective for induction than oxytocin or dinoprostone alone. The World Health Organization recommends vaginal misoprostol 25mcg every 6 hours and the American Congress of Obstetricians and Gynecologists recommends 25mcg vaginal misoprostol every three to 6 hours. Although route of administration and dosage of misoprostol has been extensively studied, little is known about the optimal dosing interval of vaginal misoprostol.MethodsThe primary objective of this study is to determine the effect of delayed vaginal misoprostol dosing, defined as any interval longer than 4.5 h, on time to vaginal delivery. Our hypothesis is that the routine dosing interval of 4 hours shortens times to vaginal delivery compared to delayed dosing, even when adjusted for the time of delay. Secondary objectives include the effect of delayed vaginal misoprostol dosing on cesarean section rate, operative vaginal delivery rate, maternal outcomes, and neonatal outcomes. We conducted a retrospective chart review of 323 inductions of labor at one academic institution. The primary outcome was the proportion of patients who achieved a vaginal delivery within 24 h. The group who received all doses of misoprostol within a 4.5 h dosing window (Routine Dosing Interval Group) was compared with the group who had any dosing deviation (Delayed Dosing Interval Group).ResultsOf 133 included patients, 64 subjects received routine interval dosing and 69 subjects received delayed interval dosing. The vaginal delivery rates within 24 h were 56% (36/64) and 20% (14/69), respectively (P < 10- 4). Spontaneous vaginal delivery rates were 86% (55/64) vs. 75% (52/69), respectively (P = .13). Kaplan Meier curves demonstrated statistically significant difference in time to vaginal delivery between groups, with a Cox Proportional Hazard ratio for routine dosing interval of 1.73 (P < 10- 5) unadjusted and 1.34 (P = .01) when adjusted for dosing delay.ConclusionsThis retrospective study demonstrates a significant increase in delay-adjusted time to vaginal delivery when doses of vaginal misoprostol are delayed past 4.5 h.
Project description:Objective To survey obstetrical provider preferences regarding use of misoprostol for induction of labor (IOL). Methods An anonymous 25-question survey was distributed at an American College of Obstetricians and Gynecologists (ACOG) joint District V and VII Meeting in 2014 to obstetrics providers. The same survey was sent electronically to local providers. A separate survey was emailed to the labor and delivery nurses at two of the teaching hospitals in Indianapolis. The surveys queried provider demographics, dosing practice for misoprostol, opinions regarding different dosing strategies, and instructions on buccal administration. Results A total of 113 (46.5%) providers responded. Of these, 92.9% used misoprostol for IOL, 73% preferred the vaginal route, 20% preferred buccal administration, and 7% oral administration. Only resident physician and midwife providers endorsed buccal route preference. Being a midwife independently predicted a preference for using buccal misoprostol (odds ratio [OR]: 125.8, 95% confidence interval [CI]: 7.9-1992.3). Additionally, 44 nurses completed the survey regarding administration techniques of buccal misoprostol. Also, 54.5% of nurses correctly instructed their patients on buccal administration techniques. Conclusion Although not extensively studied, one-fifth of providers, particularly nurse midwives, prefer buccal administration of misoprostol for IOL. The majority of nurses correctly administered buccal misoprostol. There may be a need for further study and education about buccal administration of misoprostol for IOL.
