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

BackgroundClinically, 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.MethodsThis 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+0 and 23+6 weeks’ 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.DiscussionPreterm 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.Trial registrationEudraCT Number: 2015-000456-15. Registered 11th March 2015

The influence of the introduction of national guidelines on preterm birth prevention practice: UK experience

“…2014‐003112‐36) and SUPPORT (EudraCT no. 2015‐000456‐15) encouraging randomisation between all three treatments which have been recruiting since the last questionnaire study was performed . Assuming that there is no clinically meaningful difference between these three treatments and all are subsequently proven to provide benefit, our next challenge will be to identify whether combination therapy is of added value, as this practice has started to increase.…”

“…2015-000456-15) encouraging randomisation between all three treatments which have been recruiting since the last questionnaire study was performed. 12 Assuming that there is no clinically meaningful difference between these three treatments and all are subsequently proven to provide benefit, our next challenge will be to identify whether combination therapy is of added value, as this practice has started to increase. We will need more adaptive randomised trial Cervical cerclage remains the most popular first-line treatment choice, particularly in units without specialist preterm birth prevention services.…”

Re: Effect of QUiPP prediction algorithm on treatment decisions in women with a previous preterm birth: a prospective cohort study

“…We agree that interventions need to be evaluated in high‐risk women, and these studies are underway . The QUiPP app's proven predictive performance ought not to be dismissed from this complex decision‐making process based on a misinterpretation of its application on a small and possibly unrepresentative number of women.…”

The Role of PTB Clinics: A Review of the Screening Methods, Interventions and Evidence for Preterm Birth Surveillance Clinics for High-Risk Asymptomatic Women

“…The UK-based SUPPORT trial is ongoing to compare the three treatments (71). A stronger evidencebase for pessaries may increase the use of this intervention (only 4% of UK PTB surveillance clinics use it as first line treatment), as they are less invasive and have fewer side effects than their alternatives (26, 67).…”