Background: Preterm birth is common in twins and accounts for significant mortality and morbidity. There are no effective preventative treatments. Some studies have suggested that, in twin pregnancy complicated by a short cervix, the Arabin pessary, which fits around the cervix and can be inserted as an outpatient procedure, reduces preterm birth and prevents neonatal morbidity. Objective: STOPPIT 2 aimed to evaluate the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix. Design: STOPPIT 2 was a pragmatic, open label, multicentre randomised controlled trial with two treatment group – the Arabin pessary plus standard care (intervention) and standard care alone (control). Participants were initially recruited into the screening phase of the study, when cervical length was measured. Women with a measured cervical length of ≤ 35 mm were then recruited into the treatment phase of the study. An economic evaluation considered cost-effectiveness and a qualitative substudy explored the experiences of participants and clinicians. Setting: Antenatal clinics in the UK and elsewhere in Europe. Participants: Women with twin pregnancy at < 21 weeks’ gestation with known chorionicity and gestation established by scan at ≤ 16 weeks’ gestation. Interventions: Ultrasound scan to establish cervical length. Women with a cervical length of ≤ 35 mm at 18+ 0–20+ 6 weeks’ gestation were randomised to standard care or Arabin pessary plus standard care. Randomisation was performed by computer and accessed through a web-based browser. Main outcome measures: Obstetric – all births before 34+ 0 weeks’ gestation following the spontaneous onset of labour; and neonatal – composite of adverse outcomes, including stillbirth or neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis or proven sepsis, all measured up to 28 days after the expected date of delivery. Results: A total of 2228 participants were recruited to the screening phase, of whom 2170 received a scan and 503 were randomised: 250 to Arabin pessary and 253 to standard care alone. The rate of the primary obstetric outcome was 18.4% (46/250) in the intervention group and 20.6% (52/253) in the control group (adjusted odds ratio 0.87, 95% confidence interval 0.55 to 1.38; p = 0.54). The rate of the primary neonatal outcome was 13.4% (67/500) and 15.0% (76/506) in the intervention group and control group, respectively (adjusted odds ratio 0.86, 95% confidence interval 0.54 to 1.36; p = 0.52). The pessary was largely well tolerated and clinicians found insertion and removal ‘easy’ or ‘fairly easy’ in the majority of instances. The simple costs analysis showed that pessary treatment is no more costly than standard care. Limitations: There was the possibility of a type II error around smaller than anticipated benefit. Conclusions: In this study, the Arabin pessary did not reduce preterm birth or adverse neonatal outcomes in women with a twin pregnancy and a short cervix. The pessary either is ineffective at reducing preterm birth or has an effect size of < 0.4. Future work: Women with twin pregnancy remain at risk of preterm birth; work is required to find treatments for this. Trial registration: Current Controlled Trials ISRCTN98835694 and ClinicalTrials.gov NCT02235181. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 44. See the NIHR Journals Library website for further project information.

Original languageEnglish
PublisherNIHR Health Technology Assessment programme
Number of pages94
ISBN (Print)1366-5278
Publication statusPublished - 1 Jul 2021

Publication series

NameHealth Technology Assessment
PublisherNational Co-ordinating Centre for HTA
ISSN (Print)1366-5278

Bibliographical note

Funding Information:
The research reported in this issue of the journal was funded by the HTA programme as project number 13/04/22. The contractual start date was in November 2014. The draft report began editorial review in September 2020 and was accepted for publication in February 2021. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors: Jane E Norman has received grants from government and charitable bodies for research into understanding the mechanism of term and preterm labour and understanding treatments. Within the last 3 years, Jane E Norman has acted on a Data Safety and Monitoring Board for a study involving a preterm birth therapeutic agent for GlaxoSmithKline plc (GlaxoSmithKline plc, Brentford, UK) and has provided consultancy for a small pharmaceutical company (Dilafor AB, Solna, Sweden) on drugs to alter labour progress. She was on the Health Technology Assessment (HTA) Maternal Neonatal and Child Health Panel (2013–18) and she was a member of the National Institute for Health Research (NIHR) HTA and Efficacy and Mechanism Evaluation (EME) Editorial Board (2012–14). John Norrie reports grants from the University of Edinburgh (Edinburgh, UK) during the conduct of the study, and declares that he is or has been a member of the following: HTA Commissioning Sub-Board (EOI) (2012–16), NIHR CTU Standing Advisory Committee (2017–present), NIHR HTA and EME Editorial Board (2014–19), Pre-Exposure Prophylaxis Impact Review Panel (2017–present), EME Strategy Advisory Committee (2019–present), EME – Funding Committee Members (2019–present), EME Funding Committee Sub-Group Remit & Comp Check (2019–present), HTA General Committee (2016–19), HTA Funding Committee Policy Group (formerly Clinical Studies Group) (2016–19), HTA Commissioning Committee (2010–16) and was a member of the HTA and EME Editorial Board between 2014 and 2019. Sarah Cunningham-Burley reports personal fees and other from the Wellcome Trust (London, UK), other from the University of Copenhagen (Copenhagen, Denmark), other funding from NIHR Global Health Research, personal fees from the French National Cancer Institute (Paris, France) and personal fees from the Health Research Board (Dublin, Ireland), outside the submitted work. Andrew Shennan is a member of the NIHR HTA Commissioning Committee (2018–22). Stephen C Robson was a member of the NIHR EME Funding Committee (2012–15). Steven Thornton is a trustee of a number of charities, including those that fund related research. He reports personal fees from GlaxoSmithKline plc, during the conduct of the study and outside the submitted work, and personal fees from Johnson & Johnson (Johnson & Johnson, Brunswick, NJ, USA) for consulting services. He holds positions in the Royal College of Obstetricians and Gynaecologists (London, UK) and other organisations. He was a member of the NIHR EME Strategy Advisory Committee (2018–19), EME – Funding Committee Members (2015–19), EME Funding Committee Sub-Group Remit & Comp Check (2018–19) and the Medical Research Council Multimorbidity Board (2020). Neil Marlow reports personal fees from Shire-Takeda (London, UK), Novartis Pharmaceuticals UK Ltd (London, UK) and GlaxoSmithKlein plc, outside the submitted work. Sarah J Stock declares that she is a member of the NIHR HTA General Committee (2016–22). In addition, Sarah J Stock received other research funding from the NIHR (14/32/01 QUIDS), Wellcome Trust (209560/Z/17/Z) and Chief Scientist Office (Edinburgh, UK), during the course of the study. Philip R Bennett reports personal fees and membership of a scientific panel from ObsEva (Plan-les-Ouates, Switzerland), outside the submitted work. In addition, Philip R Bennett has a patent PCT/GB1997/000529 WO1997031631 A1 ‘COX-2 selective inhibitors for managing labour and uterine contractions’ issued, a patent PCT/GB2004/001380 WO2005053705 A1 ‘Use of a cyclopentenone prostaglandin for delaying the onset and/or preventing the continuation of labour’ (priority date 2 December 2003) issued, a patent PCT/GB2016/050618 ‘Circulating miRNAs predictive of cervical shortening and preterm birth’ (pending UK filing 6 March 2015/full international filing completed 7 March 2016) issued, a patent PCT/GB2016/ 050621 ‘Rapid evaporative ionisation mass spectroscopy (REIMS) and desorbtion electrospray ionisation mass spectroscopy (DESI-MS) analysis of swabs and biopsy samples’ (pending UK filing 6 March 2015/full international filing completed 7 March 2016) pending, a patent PCT/GB2019 ‘Desorbtion electrospray ionisation mass spectroscopy (DESI-MS) analysis of swabs to predict vaginal microbiota’ (pending UK filing March 2019) pending, and a patent PCT/GB2019/ ‘Circulating miRNAs predictive of IUGR’ (pending UK filing March 2019) pending.


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