Dataset Information

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: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.

Project description:BackgroundLate-onset neonatal sepsis is a major complication in preterm neonates. Early identification of the type of infection could help to improve therapy and outcome depending on the suspected microorganism by tailoring antibiotic treatment to the individual patient based on the predicted organism. Results of blood cultures may take up to 2 days or may remain negative in case of clinical sepsis. Chemical biomarkers may show different patterns in response to different type of microorganisms.ObjectiveThe aim of this study was to develop, as a proof of concept, a simple classification tree algorithm using readily available information from biomarkers to show that biomarkers can potentially be used in discriminating in the type of infection in preterm neonates suspected of late-onset neonatal sepsis.Derivation cohortA total of 509 suspected late-onset neonatal sepsis episodes in neonates born before less than 32 weeks of gestation were analyzed. To examine model performance, 70% of the original dataset was randomly selected as a derivation cohort (n = 356; training dataset).Validation cohortThe remaining 30% of the original dataset was used as a validation cohort (n = 153; test dataset).Prediction modelA classification tree prediction algorithm was applied to predict type of infection (defined as no/Gram-positive/Gram-negative sepsis).ResultsSuspected late-onset neonatal sepsis episodes were classified as no sepsis (80.8% [n = 411]), Gram-positive sepsis (13.9% [n = 71]), and Gram-negative sepsis (5.3% [n = 27]). When the derived classification tree was applied to the test cohort, the overall accuracy was 87.6% (95% CI, 81.3-92.4; p = 0.008). The classification tree demonstrates that interleukin-6 is the most important differentiating biomarker and C-reactive protein and procalcitonin help to further differentiate.ConclusionWe have developed and internally validated a simple, clinically relevant model to discriminate patients with different types of infection at moment of onset. Further research is needed to prospectively validate this in a larger population and assess whether adaptive antibiotic regimens are feasible.

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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