High or low dose Syntocinon®, for induction of labour in nulliparous women: a double blind, randomised controlled trial (The iHOLDS Trial)

Research question To determine the clinical effectiveness and costs of a high dose compared to the current standard dose regimen of Syntocinon for nulliparous women for whom it is prescribed as part of induction of labour. Background Evidence is limited, with mixed results and unclear findings for clinically relevant indicators to guide practice. There are no ongoing trials and there is need for a definitive one. Aims and objectives To provide robust evidence of clinical effectiveness and costs of high dose compared to standard dose regimen of Syntocinon for nulliparous women when prescribed during induction of labour. Methods Multicentre, randomised, double blind, controlled trial in approximately 30 UK maternity units. Target population Nulliparous women with a singleton pregnancy undergoing induction of labour for whom Syntocinon is prescribed who clinicians are willing to randomise and who consent to participate. Health technologies assessed The high dose regimen of Syntocinon (4mU/min increasing every 30 minutes to a maximum of 64mU/min) compared to the standard dose regimen recommended by national guidance (2mU/min increasing every 30 minutes to a maximum 32mU/min). Treatment allocation: Randomisation will be by telephone available 24 hours a day to an automated secure system which includes a minimisation algorithm to ensure balance with respect to important prognostic factors. Outcomes Primary outcome; Caesarean section (CS). Secondary outcomes: maternal and neonatal birth outcome data that are routinely collected and include the recently published Core Outcome set and a quantitative assessment of maternal psychological outcomes using validated tools two weeks after birth via mobile phone technology. An in-trial cost comparison will compare the costs associated with a high dose regimen of Syntocinon with the standard dose. We will ask for consent from women and their babies so that long term follow-up is possible. Sample size Our survey of 22 obstetric units indicated that the average rate of caesarean section in nulliparous women undergoing induction and given standard-dose Syntocinon to be approximately 30% (95%CI: 28%-32%). To detect an absolute reduction of 6% (equivalent to a 20% relative reduction) with 90% power (p=0.05) would require 2400 women in total (including a conservative 4% inflation for any loss to follow-up or withdrawals). Analysis The analysis will be by intention to treat. Point estimates, 95% confidence intervals and p values from two sided tests will be calculated for all outcomes. Timelines for delivery The trial will last 36 months. The set-up period is nine months and an internal pilot will form the first eight months of recruitment. This has clear, realistic recruitment targets, including protocol adherence and data collection. Recruitment will take 21 months in total, followed by a 6 month close down. Anticipated impact and dissemination We have a comprehensive plan for dissemination and impact that utilises multiple communication methods and involving both informing national guidelines as well as both clinicians and women