Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes (C-STICH)

Approximately 50,000 babies are born prematurely. Approximately 1,500 of them die. Moreover, an early birth puts survivors at risk of serious long-term disabilities. These outcomes pose a significant burden on parents and have significant economic implications on health services. It is estimated that 10% of healthcare recourses in developed countries are spent on treating diseases in children resulting from preterm birth (PTB). Cervical incompetence is one of the important causes of PTB for which cerclage has been one of the established management options. A recent Cochrane review showed a trend to a reduction in neonatal death and neonatal morbidity, neither alone was significant. Traditionally, clinicians have used Mersilene tape (a braided suture) for cervical cerclage because of its perceived strength and ease of removal. However, braided sutures, particularly mesh-like macroporous sutures, have been associated with an increased risk of infection and operative complications in other surgical disciplines. Both low-grade chronic and acute infections are risk factors for PTB. Some surgeons opt to use monofilament sutures for cerclage. Conversely, detractors suggest that monofilament sutures are not as strong and can potentially traumatise the cervix at insertion. However, these claims are not substantiated by any scientific or clinical evidence. Hypothesis: Based on the above, we hypothesise that the use of monofilament sutures are associated with reduced risk of miscarriage and perinatal mortality after cerclage. Preparatory work: We conducted a national survey of O&G consultants, which confirmed variability in practice - with 86% and 14% reported using braided and monofilaments sutures for cerclage procedures respectively. Significantly, 75% of respondents stated that there was no guidance for which suture material to use within their units. We conducted a systematic literature review and identified only 2 non-randomised studies (NRS). The NRS meta-analysis demonstrated that monofilament sutures, compared to Mersilene, were associated with a pregnancy loss rate of 4% compared to 16% respectively (OR 0.24 95% CI 0.06 - 0.96). We ran a small feasibility RCT to test protocol, recruitment strategy, decline rates and data collection (ISRCTN17866773). Aim: The overall aim is to investigate the clinical effectiveness of nylon monofilament suture material in reducing pregnancy loss rate following cervical cerclage compared to the Mersilene suture. Plan: The original sample size for C-STICH was informed by our meta-analysis of the available evidence with some allowance made for the fact that this evidence was non-randomised. Here, the pregnancy loss rate was 7.1% with monofilament sutures compared to 19% with braided sutures, a reduction of 66% (RR: 0.34, 95% CI: 0.18 to 0.63). A total sample of 326 women would be enough to detect a difference of this size with 90% power (p=0.05). However, we inflated this to a total sample target of 900 (gaining full outcome data on 878) which enabled us to detect a more plausible relative reduction of 41% (19% with braided to 11.2% with monofilament) with 90% power (p=0.05). Given there was some uncertainty around the estimates of pregnancy loss, it was agreed that the DMEC would monitor the overall (pooled) event rate throughout the study to ascertain how any deviation from the original assumptions would impact on the sample size calculation. Indeed, in July 2017 the DMEC advised the C-STICH TMG that the current estimate of pooled event rate was lower than anticipated and may impact on the trials ability to detect a difference between groups, should one exist. They advised that to maintain 90% power to detect the same relative reduction of 41% the sample size should be increased to 2050 women. Benefits: If the currently perceived benefit of monofilament sutures is confirmed, this policy will be adopted nationally and can potentially save more than 300 babies from dying per annum in the UK. Moreover, reducing the risk of prematurity will reduce neonatal unit and hospital stay, the morbidity associated with early gestation and the associated long-term morbidity. The marginal difference in cost of the sutures will ensure any reduction of pregnancy loss is cost-effective.