Balloon Catheter Versus Propess for Labour Induction (PROBIT-F)

The study will be conducted over two sites: St. George's Hospital in London, and Medway Hospital in Kent. Women requiring induction of labour (IOL) at term will be invited to participate in the study, where they will be randomised to either the trans-cervical balloon catheter or the vaginal prostaglandin 10mg (Propess).

Consent to enter this study will be obtained after 37+0 weeks after a full account has been provided of its nature, purpose, risks, burdens and potential benefits. Patients will have the opportunity to consider whether they wish to take part in the study, up to a maximum of 72 hours. For prolonged pregnancy (41+0 weeks), Induction of labour is generally booked at 41+3 weeks, giving a 3-day time period to think about participation. Periods shorter than 72 hours will be permitted if the woman felt that further deliberation will not lead to a change in her decision, and provided the person seeking consent is satisfied that the woman has fully retained, understood and deliberated on the information given. This provision has been made with the support of our patient advisory group. Likewise, periods longer than 72 hours will be permitted should the woman request this. The Investigator or designee will explain that the women are under no obligation to enter the trial and that they can withdraw at any time during the trial, without having to give a reason. A copy of the signed Informed Consent Form will be given to the study participant. The original signed consent form (ICF) will be retained at the study site in the Investigation site file (ISF) and a copy of the ICF along with a copy of the Participant Information Sheet (PIS) will be retained in the maternity notes.

If new safety information results in significant changes to the risk-benefit assessment, the consent form will be reviewed and updated if necessary. All subjects, including those already treated, will be informed of the new information, given a copy of the revised consent form and asked to re-consent if they choose to continue in the study.

In order to ensure a similar distribution between treatment groups in important characteristics thought to affect outcomes, including site and parity, allocation will be random and stratified by site (St. George's and Medway) and parity (nulliparous and multiparous). Participants will be allocated using block randomisation so as to ensure similar numbers of participants in the treatment groups. Whilst blocks of size four are proposed, advice regarding random block sizes (including four, six and eight) will be sought from the Kings Clinical Trials Unit (CTU).

Participants and midwives will not be blinded to the treatment allocation. The trial statistician will be blinded to group allocation.

The trial will be analysed using an intention to treat approach. Induction of labour with Propess: 10mg insert will be introduced in the posterior vaginal fornix close to the cervix as recommended by the manufacturer. Women will undergo monitoring of fetal condition and uterine activity by cardio-tocography (CTG) according to the existing protocol. It will be discontinued once the CTG is deemed to be normal. The woman will be allowed home with instructions to return to the hospital at an agreed time, 18-24 hours later, or if in labour, whichever was earlier. On the following morning the pessary will be removed, and artificial rupture of membranes (ARM) attempted.

Induction of labour with balloon catheter: The woman should be positioned in the lithotomy position and insert a large vaginal speculum to gain cervical access. The cervix must be cleaned appropriately to prepare for device insertion. Insert the device into the cervix and advance until both balloons have entered the cervical canal. Inflate the uterine balloon with 40ml Sodium Chloride (NaCL) 0.9% using a standard luer lock 20ml syringe through the red check-flo valve marked U.

Once the uterine balloon is inflated, the device is pulled back until the balloon is against the internal cervical os. The vaginal balloon is now visible outside the external cervical os. Inflate the vaginal balloon with 20ml NaCl 0.9% using a standard luer lock 20ml syringe through the green Check-Flo valve marked V. Once the balloons are situated on each side of the cervix and the device is fixed in place, remove the speculum. Add more fluid to each balloon in turn, in 20ml increments until each balloon contains 80ml (maximum volume of fluid) Do NOT overinflate the balloons. If desired the end of the catheter may be taped to the woman's thigh.

Women will undergo monitoring of fetal condition and uterine activity by cardio-tocography (CTG) according to the existing protocol. It will be discontinued when the CTG is deemed to be normal. The woman will be allowed home with instructions to return to the hospital an agreed time, 18-24 hours later, or if in labour, whichever was earlier. When the participant returns, the balloon catheter will be removed, and artificial rupture of membranes (ARM) attempted.

If artificial rupture of membranes was not possible, this will be considered as treatment failure and alternative ways of achieving delivery will be sought as per local guidelines and followed. Unsuccessful placement of the balloon or inability to perform ARM will be considered as treatment failure and an alternative method of IOL will be used.

Survey

1. Recruitment Survey. Questionnaires will be given to all women at the point of recruitment. Women who decline will be invited to complete the questionnaire anonymously and it will be made clear that the aim of the survey is solely to improve future care through assessing the feasibility of the balloon catheter with no implications for their own care. The schedule will comprise closed questions plus comment boxes to examine women's understanding of the trial, their reasons for participation or declining. A detailed process log will also be maintained to identify the numbers and proportions of women who accept randomisation and those who withdraw after entry to the trial.
2. Follow-up questionnaire for participants: We will use a slightly modified form of questionnaire used previously used by Henry et al (2013) to assess patient satisfaction, experience of participating, experience of the IoL process using either method including pain or discomfort, experience of outpatient IoL and level of information provided.

Qualitative study In addition, qualitative data will be gathered for a sample of participants to enable a fuller exploration of the trial feasibility in two stages.

1. To gain a better understanding of feasibility and effective trial procedures for a trial where interventions cannot be blinded and preferences may be strong. A researcher with experience of studies of trial processes, independent of the trial management, will (with consent of women and professionals) observe a sample of recruitment discussions to ascertain how information is provided and to understand in greater depth how choices about trial participation are made. The focus will include diversity issues, as typically participation in randomized controlled trials (RCTs) is socially and ethnically skewed. This will be a consecutive sample continued until saturation to include women allocated randomly and those in the preference arms, those women who decline and a cross-section of social and ethnic groups. Estimated sample: 40 recruitment observations.
2. Women included in observations who consented to participate in the trial will be invited to participate in semi structured interviews postnatally, to explore their experience of participating and of the IoL process using either method, their experience of outpatient IOL and any further reflections. Those who provide telephone details will be contacted postnatally to confirm whether they are still happy to participate in an interview, following checks of neonatal outcomes. All women and professionals will be assured of confidentiality and their rights to decline consent for observation or interview. A thematic framework analysis will be conducted focused on lessons for trial feasibility, design, recruitment and retention, and patient experiences of cervical ripening using either method for induction in an outpatient setting. This approach enables consideration of unintended as well as anticipated consequences plus a fuller understanding of how women and their birth partners experience induction of labour and whether an outpatient approach confers advantages in terms of experience and satisfaction since, despite this being a key rationale for an outpatient approach, patient experiences of different induction approaches is an under-explored area. The number of interviews will be guided by data saturation, with a maximum potential sample of 40.