title: Rationale and design of SuPPoRT: a multi-centre randomised controlled trial to compare three treatments: cervical cerclage, cervical pessary and vaginal progesterone, for the prevention of preterm birth in women who develop a short cervix.
abstract: Clinically, once a woman has been identified as being at risk of spontaneous preterm birth (sPTB) due to a short cervical length, a decision regarding prophylactic treatment must be made. Three interventions have the potential to improve outcomes: cervical cerclage (stitch), vaginal progesterone and cervical pessary. Each has been shown to have similar benefit in reduction of sPTB, but there have been no randomised control trials (RCTs) to compare them.
  
  
  
  This open label multi-centre UK RCT trial, will evaluate whether the three interventions are equally efficacious to prevent premature birth in women who develop a short cervix (<25 mm on transvaginal ultrasound). Participants will be asymptomatic and between 14+0and 23+6weeks' gestation in singleton pregnancies. Eligible women will be randomised to cervical cerclage, Arabin pessary or vaginal progesterone (200 mg once daily) (n = 170 women per group). The obstetric endpoints are premature birth rate <37 weeks' of gestation (primary), 34 weeks and 30 weeks (secondary outcomes) and short-term neonatal outcomes (a composite of death and major morbidity). It will also explore whether intervention success can be predicted by pre-intervention biomarker status.
  
  
  
  Preterm birth is the leading cause of perinatal morbidity and mortality and a short cervix is a useful way of identifying those most at risk. However, best management of these women has presented a clinical conundrum for decades. Given the promise offered by cerclage, Arabin pessary and vaginal progesterone for prevention of preterm birth in individual trials, direct comparison of these prophylactic interventions is now essential to establish whether one treatment is superior. If, as we hypothesise, the three interventions are equally efficacious, this study will empower women to make a choice of treatments based on personal preference and quality of life issues also explored by the study. Our exploratory analysis into whether the response to intervention is related to the pre-intervention biomarker status further our understanding of the pathophysiology of spontaneous preterm birth and help focus future research questions.
  
  
  
  EudraCT Number: 2015-000456-15 . Registered 11th March 2015.
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Hezelgrave
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Watson
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ridout
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Falak
authors.initials: F
authors.lastname: Diab
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Evonne
authors.initials: E
authors.lastname: Chin-Smith
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK. rachel.tribe@kcl.ac.uk.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Tribe
authors.affiliation: Division of Women's Health, Faculty of Life Sciences & Medicine, King's College London, Women's Health Academic Centre King's Health Partners, 10th Floor North Wing, St Thomas' Hospital Campus, London, SE1 7EH, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Shennan
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D023802:Cerclage, Cervical / Q000379:methods*; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D010570:Pessaries; D011247:Pregnancy; D011248:Pregnancy Complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000209:etiology / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D011372:Progestins; D011374:Progesterone
keywords: Arabin pessary; Biomarkers; Cerclage; Cervical length; Preterm birth; Progesterone