Pessary or cerclage (PC study) to prevent recurrent preterm birth: a non-inferiority, randomised controlled trial.

Background: Previous spontaneous preterm birth (sPTB) is a strong risk indicator for recurrent preterm birth (PTB). Cervical cerclage is an accepted intervention to prevent recurrent PTB in high risk patients. Cervical pessary might be a less invasive alternative. The objective of this study is to determine whether a cervical pessary is non-inferior to cerclage in the prevention of recurrent PTB.
Methods: We performed an international, open-label, non-inferiority, randomised controlled trial in 21 hospitals between March 2014 and December 2022. We included singleton pregnancies with an indication for cerclage based on either multiple previous sPTBs <34 weeks or with a previous sPTB <34 weeks and an asymptomatic mid-trimester short cervix (≤25 mm). Randomisation was 1:1, stratified by centre and indication, to cervical pessary or vaginal cerclage. Primary outcome was PTB <32 weeks. Secondary outcomes included (s)PTB rates, obstetric, and maternal outcomes and a composite of adverse perinatal outcomes including perinatal mortality and severe neonatal morbidity. Analysis was by intention-to-treat. Treatment effect was expressed as relative risk (RR), absolute risk difference (aRD) and 95% confidence intervals (CI). Sample size was calculated at 400 participants with a non-inferiority margin for pessary of 10%, meaning that non-inferiority is proven if the upper limit of the CI of the risk difference is <10%. Trial registration at ICTRP: NL-OMON26958.
Findings: We randomised 261 participants to pessary (n = 133) or cerclage (n = 128). After the third interim analysis (n = 228 participants), recruitment was halted due to safety concerns and the apparent challenge in establishing non-inferiority of pessary treatment. PTB <32 weeks occurred in 44/130 cases after pessary vs 30/125 cases after cerclage (33.8% vs 24.0% aRR 1.4, 95% CI 0.95-2.1, p = 0.09, aRD 9.8% 95% CI -1.2 to 20.9). The composite of adverse perinatal outcomes occurred in 42 cases after pessary compared to 29 cases in cerclage (32.2% vs 23.2%; RR 1.4 95% CI 0.93-2.1 p = 0.1) and consisted mainly of perinatal death (22.3% vs 14.4% RR 1.5 95% CI 0.9-2.6 p = 0.1).
Interpretation: Non-inferiority of cervical pessary compared to cerclage in preventing recurrent PTB <32 weeks was not proven. Cerclage is the recommended treatment.
Funding: ZonMw (#837002406), a Dutch Organisation for Health Research and Development.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. BMT reports receiving consulting fees for participation to the advisory board of Effik, Pierre-Favre and Sanofy, received payment for legal expert testimonies in malpractice cases in obstetrics and received a device to measure cervical softening from Pregnolia. BWM received an investigator grant from NHMRC. MAO received research grants for studies on the prevention of preterm birth, reports expenses paid for organization of preterm birth symposium, is chairman of the Fetal-Maternal Medicine board of the Dutch society of Obstetrics & Gynecology and chairman of the scientific committee of the Fetal-Maternal-Medicine Board. MAO and EP are board members of Stichting Stoptevroegbevallen, a non-profit organization supporting preterm birth research and received payments to the institution. EP received research grants for studies on prevention and treatment of preterm birth and the fetal microbiome.
(© 2024 The Author(s).)