Title: Three-arm randomised trial of Arabin pessary, cervical cerclage and progesterone to prevent spontaneous preterm birth in an asymptomatic high risk cohort: a feasibility study
Funder: Department of Health (England)

Abstract: BACKGROUND: Preterm birth remains the leading cause of neonatal morbidity and mortality with no evidence of reduction in incidence despite recent advances in obstetric care2. This condition has huge emotional impact on parents and the financial cost of a preterm birth to the public sector is in excess of £2.95 billion annually3. There is evidence to justify the use of treating asymptomatic high-risk women with a short cervix using an Arabin pessary, cervical cerclage or vaginal progesterone to reduce rates of spontaneous preterm birth. A randomised trial to evaluate if there is a singular most effective, safe and acceptable treatment for patients is required. We plan a preliminary feasibility study to establish if a definitive trial is practicable. AIM: The overarching aim is to assess the feasibility for a larger multicentre randomised trial to compare three evidenced based treatments in high-risk asymptomatic women in pregnancy with a short cervix, including: - Feasibility of recruitment and retention to a randomised trial pilot in the preterm labour clinic setting - Exploring patient acceptability of individual treatment interventions and assessing preferences for treatments - Modelling techniques for economic analysis used in a definitive trial. DESIGN: A three-arm non-blinded randomized feasibility study with equal randomization with a qualitative interpretive study, utilizing semi-structured face-to-face, telephone interviews and focus groups. SETTING: Two UK Preterm Labour Clinics in Tertiary Referral Settings. PARTICIPANTS: High risk asymptomatic patients attending preterm labour clinic with singleton pregnancy. Women will be randomised if they require treatment for a short cervix, defined as INTERVENTION: Participants will be randomised 1:1:1 to receive Arabin pessary, progesterone 200mg pv nocte or cervical cerclage. OUTCOMES: The main outcome for this study is feasibility for a definitive trial. Feasibility of recruitment will be measured by recruitment rates in one year recruitment period. Feasibility of the study design will be assessed by rates of drop out or cross-over from the trial arms, adherence to protocol, loss to short term follow up and deliverability of all treatment arms in each hospital unit. Acceptability of trial arm treatments will be explored with women using established qualitative methods; data will be analysed thematically. The economic analysis would enable a tentative comparative cost utility estimate to be derived for each technique BENEFIT TO PATIENTS AND NHS: Preterm birth may have a significant impact upon the health of babies, and given the frequency of preterm births, knowledge of even the smallest potential improvement in neonatal outcomes between approaches in the prevention of spontaneous preterm birth is likely to lead to appreciable improvements in the management of this condition. Such improvements, if generalised throughout the NHS are likely to generate significant health benefits to women and sizable resource savings to the NHS, and as such, this research offers a considerable opportunity to generate evidence that will inform clinical decision making with regard to the optimisation of methods to reduce the health and resource losses associated with PTB. Qualitative data and exploration of women's attitudes and experiences is invaluable in improving research design for future women and has a discernible impact on local service provision. Creating a better understanding of this cohort and engaging both English and non-English speakers in research will allow for improved generalizability of results and provide opportunities for local services to better respond to their needs. Differences in intervention acceptability across ethnic groups may allow for increasingly culturally specific and sensitive counseling regarding treatment choice at this highly stressful stage of pregnancy.


Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH