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Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study.

ABSTRACT: The aim was to investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour.This was a randomized, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48?h to women in spontaneous preterm labour between 30(0/7) and 35(6/7) ?weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to delivery, preterm delivery and safety.Uterine quiescence was achieved in 62% of women who received retosiban (n?=?30) compared with 41% who received placebo (n?=?34). The relative risk (RR) was 1.53 (95% credible interval [CrI] 0.98, 2.48; NS). Retosiban resulted in a significant increase in time to delivery compared with placebo (mean difference 8.2?days, 95% CrI 2.7, 13.74). This difference was consistent across all gestational ages. The proportion of preterm births in the retosiban and placebo groups was 18.7% (95% CrI 7.4%, 33.7%) and 47.2% (95% CrI 31.4%, 63.4%), respectively. The RR of preterm birth in women treated with retosiban was 0.38 (95% CrI 0.15, 0.81). There were no deliveries within 7?days in the retosiban group, but there were six (17.6%) births in the placebo group. The maternal, fetal and neonatal adverse events were comparable in the retosiban and placebo groups.Intravenous administration of retosiban in women with spontaneous preterm labour was associated with a greater than 1 week increase in time to delivery compared with placebo, a significant reduction in preterm deliveries, a non-significant increase in uterine quiescence and a favourable safety profile.

SUBMITTER: Thornton S

PROVIDER: S-EPMC4594710 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study.

Thornton Steven S Miller Hugh H Valenzuela Guillermo G Snidow Jerry J Stier Brendt B Fossler Michael J MJ Montague Timothy H TH Powell Marcy M Beach Kathleen J KJ

British journal of clinical pharmacology 20150601 4

<h4>Aim</h4>The aim was to investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour.<h4>Methods</h4>This was a randomized, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48 h to women in spontaneous preterm labour between 30(0/7) and 35(6/7) weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to deli ...[more]

PMID: 25819462

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Project description:BackgroundMechanical labour induction with a transcervical balloon is as effective as pharmacological methods, with fewer adverse effects. Its use has been limited to labour induction with an unfavourable cervix able to retain the balloon. We have developed an innovative approach using 2-3 balloons side-by-side to extend the benefits of mechanical labour induction/augmentation with a favourable cervix without having to resort to amniotomy or uterotonics.ObjectivesTo assess the effectiveness of side-by-side balloons for extended labour induction/augmentation.MethodsWe conducted a single arm proof of concept trial at Princess Marina Hospital (PMH) in Gaborone, Botswana. Participants were assessed as unsuitable for single balloon labour induction based on a modified Bishop cervical score of 7 or more. Three Foley catheters taped symmetrically side by side were passed through the cervix and inflated with 60mls each. Traction was applied with a weight of 250mls water suspended over the bed-end. The use of uterotonics, time from induction to birth, mode of birth, Apgar scores and adverse maternal and neonatal outcomes were recorded. Participants' satisfaction with the method of labour induction was assessed using a descriptive scale.ResultsWe enrolled 20 participants of whom two were nulliparous. Indications for labour induction were mainly late term (70%) and hypertensive disorders of pregnancy (25%). The mean cervical score was 7.2. Overall, 17 (85%) of the participants achieved a vaginal birth, of whom 5 required oxytocin for labour augmentation. Four of these had requested removal of the balloons, one due to discomfort and three felt the process was taking too long. Three participants underwent caesarean birth. The mean time from initiation of labour induction to vaginal birth was 16 h (standard deviation (SD) 8.4) and 20 h for caesarean birth (SD 10.5). There were no 5-minute Apgar scores below 7 nor neonatal admissions. One baby required brief resuscitation. There were no adverse maternal outcomes.ConclusionThis proof-of-concept study suggests that use of side-by-side balloons in participants with favourable cervix is effective in achieving vaginal birth in most participants without uterotonics or amniotomy. There were no adverse outcomes, though the study was too small to exclude the possibility of rare adverse outcomes. This offers a novel option for labour induction/augmentation, particularly where uterotonics or amniotomy are best avoided such as prior caesarean birth, vertical infection transmission risk and in settings with limited capacity for fetal surveillance. The results clearly justify larger randomized trials to evaluate this novel approach with greater precision. On the basis of the current study we are developing a purpose-designed balloon for extended balloon labour induction.

Project description:A hypothesis of preterm parturition is that the pathogenesis of spontaneous preterm birth (sPTB) may be associated with an inflammatory process. Based on this theory, we have hypothesized that an inflammatory biomarker, procalcitonin (PCT), may be a good predictive marker of sPTB at the admission for threatened preterm labour (TPL). The present study was aimed to investigate the association between serum PCT and sPTB in women with TPL and to evaluate whether PCT levels may predict sPTB in women with TPL within 7 or 14 days.In a prospective observational laboratory-based study, women with singleton pregnancies, TPL between 24 and 36 weeks and intact membranes, were enrolled between January 2014 and June 2016. Participants received routine medical management of TPL (tocolysis with atosiban, antenatal corticosteroids, and biological tests at admission (C-reactive protein, white blood cell count, and PCT measured on electrochemiluminescence immunoassay)). The primary endpoint was sPTB before 37 weeks of gestation. The value of serum PCT levels to predict sPTB within 7 or 14 days were evaluated using receiver-operating curves (ROC) analysis.A total of 124 women were included in our study. PCT levels did not statistically differ between women with sPTB (n?=?30, 24.2%) and controls (n?=?94) (median in ng/mL [interquartile range]: 0.043 [0.02-0.07] compared to 0.042 [0.02-0.13], respectively; P?=?0.56). PCT levels did not also statistically differ between women with sPTB within 7 days (n?=?7, 5.6%) or 14 days (n?=?12, 9.7%) after testing and controls. Moreover, subgroup analysis revealed no difference among PCT levels at admission between 24 and 28 weeks, between 28 and 32 weeks and over 32 weeks, and controls. On the basis of the receiver-operating characteristic curve, the highest sensitivity and specificity corresponded to a PCT concentration of 0.038 ng/mL, with poor predictive values for sPTB within 7 or 14 days.Serum PCT was not relevant to predict sPTB within 7 or 14 days in women admitted with TPL between 24 and 36 weeks, and thus it is not a suitable biological marker to confirm the hypothesis of an inflammatory process associated with preterm parturition.Clinicaltrials.gov ( NCT01977079 ), Registered 24 October 2013.

Dataset Information

Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study.

Publications

Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study.

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