Dataset Information

Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

ABSTRACT: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ?40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ?4. In Part A of the study, safety evaluation of three escalating doses of serelaxin (7.5, 25 or 75 ?g/kg/day) or placebo was performed in 22 subjects admitted to the hospital 24 h prior to scheduled induction (n?=?7, 4, 4, and 7 subjects, respectively). The highest safe dose from Part A and placebo were then tested in Part B for safety and cervical ripening (n?=?25 subjects/arm). Planned randomisation ratio was of 4:2 (serelaxin:placebo) for each dose group in Part A and 1:1 for Part B. For analysis, subjects in Part B were pooled with those receiving the same dose in Part A and all subjects receiving placebo were pooled. The primary efficacy endpoint was change from baseline in Bishop score at 6, 12 and 24 h or end of study drug administration. Maternal safety evaluations included adverse events and vital signs through 4 weeks. Fetal assessments included serial heart rate monitoring and nonstress testing. Neonatal assessments included Apgar scores, NICU admissions, and adverse events through 4 weeks.Overall, 74 subjects were randomized and 72 were treated. There were no significant differences between the groups receiving the highest safe dose of serelaxin (75 ?g/kg/day) and placebo in the primary or secondary efficacy endpoints. Changes from baseline in Bishop score at 24 h were 4.19?±?1.9 and 3.26?±?2.26 in the pooled placebo and serelaxin groups, respectively (p?=?0.2507). Serelaxin was well tolerated and no anti-serelaxin antibodies were detected in either subjects or neonates.Serelaxin infusion at the end of pregnancy was well tolerated but did not advance cervical ripening.Clinicaltrials.gov identifier NCT00259103 (15 November 2005).

SUBMITTER: Weiss G

PROVIDER: S-EPMC5011832 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

Weiss Gerson G Teichman Sam S Stewart Dennis D Nader David D Wood Susan S Breining Peter P Unemori Elaine E

BMC pregnancy and childbirth 20160905

<h4>Background</h4>Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.<h4>Methods</h4>This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 we ...[more]

PMID: 27596360

Similar Datasets

Project description:Due to rising rates of labour induction in industrialised countries, safe and effective methods of induction have once again become a focus of interest and research. Prostaglandins are effective for cervical ripening and induction of uterine contractions. They do, however, cause overstimulation of the uterus in up to 20 % of cases, sometimes causing changes in fetal heart rate. Transcervical balloon catheters provide an alternative to prostaglandins for labour induction and have been used for this purpose for almost 50 years. This induction method has experienced a recent renaissance in clinical practice that is reflected in an annually rising number of publications on its use. Balloon catheters allow gentle ripening of the cervix without causing uterine overstimulation. The two catheters available are the Foley catheter (off-label use) and the double balloon catheter, which is licensed for use in induction of labour. Both are as effective as prostaglandins, and do not increase the risk of infection to mother or child. Catheter induction also requires less monitoring compared to prostaglandins resulting in improved patient satisfaction. Balloon catheters provide a useful and promising option to achieve vaginal delivery despite failed prostaglandin induction. Intravenous oxytocin is nevertheless required in up to 85 % of cases for adequate induction/augmentation of contractions. Balloon catheters, vaginal PGE2 and misoprostol are equally effective in the context of an unripe/unfavourable cervix, the rate of uterine hyperstimulation being significantly lower, and the need for oxytocin significantly higher for catheters. Balloon catheters are increasingly being used in combination or sequentially with oral/vaginal misoprostol, although there is currently inadequate published data on the subject. International guidelines recommend the use of balloon catheters for labour induction with an unripe cervix (also following previous caesarean section) as an alternative to prostaglandins, particularly when these are not available or are contraindicated.

Project description:BackgroundThere is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis. However, there are concerns about the use of prostaglandins, the agents commonly used in hospital settings for this indication, because prostaglandins induce uterine contractions that may lead to fetal hypoxia. Indeed, in a recent study we demonstrated abnormalities in 9% of fetal heart rate tracings performed following prostaglandin induced cervical ripening at term. In contrast, we confirmed in the same study that isosorbide mononitrate (IMN) (administered on an inpatient basis) was both effective in inducing cervical ripening at term, and was associated with no associated fetal heart rate abnormalities.Methods/designThe aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour. Specifically, we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery, decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour, compared with placebo treatment. In the study described here (the "IMOP" study), women scheduled for induction of labour at term, and who require pre-induction cervical ripening will be randomised to self-administer at home either IMN 40 mg, or a placebo, each vaginally, at 48 hours, 32 hours and 16 hours before scheduled hospital admission. After admission to hospital, treatment will revert to the usual induction of labour protocol. We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery, the costs to the health service of induction of labour, and women's experience of induction of labour in the two groups.DiscussionThis trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term. We will study a formulation of IMN which is cheap and widely available. If the treatment is effective, acceptable to women, and cost effective, it could be implemented into obstetric practice worldwide.Trial registrationThe trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRTN39772441.

Project description:INTRODUCTION:Induction of labour (IOL) is a common practice. In Australia, up to 40% of women undergoing labour induction will ultimately have a caesarean section. As a biological role for melatonin in the onset and progress of labour has been demonstrated, we aim to test the hypothesis that addition of melatonin will reduce the need for caesarean section. METHODS AND ANALYSIS:This is a double-blind, randomised, placebo-controlled trial in women undergoing IOL at term. We plan to randomise 722 women (1:1 ratio) to receive either melatonin (four doses of 10?mg melatonin: first dose-in the evening at the time of cervical balloon or Dinoprostone PGE2 vaginal pessary insertion, second dose-at time of oxytocin infusion commencement, third dose-6?hours after the second dose, fourth dose-6?hours after the third dose) or placebo (same dosing regime). Participants who are having artificial rupture of the membranes only as the primary means of labour induction will receive up to three doses of the trial intervention. The primary outcome measure will be the requirement for a caesarean section. Secondary outcomes will include duration of each stage of labour and time from induction to birth, total dose of oxytocin administration, epidural rate, indication for caesarean section, rate of instrumental deliveries, birth within 24?hours of induction commencement, estimated blood loss, Apgar score at 5?min, neonatal intensive care unit admissions and participant satisfaction. Maternal melatonin levels will be measured immediately before commencement of the oxytocin intravenous infusion and 3?hours after and at the time of birth in order to determine any differences between the two trial arms. ETHICS AND DISSEMINATION:The study is conducted in accordance with the conditions of Monash Health HREC (RES-17-0000-168A). Findings from the trial will be disseminated through peer-reviewed publications and conference presentations. PROTOCOL VERSION:V.7.0, 30 July 2019. TRIAL REGISTRATION NUMBER:ACTRN12616000311459, Universal trial number: (UTN) U1111-1195-3515.

Project description:Objective This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals.Study design This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (L&D) stay. Multivariable analysis was used to adjust for patient characteristics.Results Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96-1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92-1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83-1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16-0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29-0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40-1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter L&D stay (adjusted mean difference = -1.97 hours, 95% CI: -3.45 to -0.49 and -5.92 hours, 95% CI: -7.07 to -4.77, respectively), compared with PGE.Conclusion In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of L&D stay was the shortest with concurrent Foley-oxytocin.Key points· Adverse maternal outcomes are similar among different methods of cervical ripening in low-risk women.. · Adverse neonatal outcomes are less frequent with use of Foley alone or in combination with PGE.. · The use of Foley alone, or in combination with other agents, appears to be beneficial..

Project description:INTRODUCTION:Labour induction in women with a previous caesarean delivery currently uses vaginal prostaglandin E2 (PGE2), which carries the risks of uterine hyperstimulation and scar rupture. We aim to compare the efficacy of mechanical labour induction using a transcervically applied Foley catheter balloon (FCB) with PGE2 in affected women attempting trial of labour after caesarean (TOLAC). METHODS AND ANALYSIS:This single-centre non-inferiority prospective, randomised, open, blinded-endpoint study conducted at an academic maternity unit in Singapore will recruit a total of 100 women with one previous uncomplicated caesarean section and no contraindications to vaginal delivery. Eligible consented participants with term singleton pregnancies and unfavourable cervical scores (?5) requiring labour induction undergo stratified randomisation based on parity and are assigned either FCB (n=50) or PGE2 (n=50). Treatments are applied for up to 12?hours with serial monitoring of the mother and the fetus and serial assessment for improved cervical scores. If the cervix is still unfavourable, participants are allowed a further 12?hours' observation for cervical ripening. Active labour is initiated by amniotomy at cervical scores of ?6. The primary outcome is the rate of change in the cervical score, and secondary outcomes include active labour within 24?hours of induction, vaginal delivery, time-to-delivery interval and uterine hyperstimulation. All analyses will be intention-to-treat. The data generated in this trial may guide a change in practice towards mechanical labour induction if this proves efficient and safer for women attempting TOLAC compared with PGE2, to improve labour management in this high-risk population. ETHICS AND DISSEMINATION:Ethical approval is granted by the Domain Specific Review Board (Domain D) of the National Healthcare Group, Singapore. All adverse events will be reported within 24?hours of notification for assessment of causality. Data will be published and will be available for future meta-analyses. TRIAL REGISTRATION NUMBER:NCT03471858; Pre-results.

Dataset Information

Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

Publications

Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets