To compare the effectiveness of a cervical pessary and vaginal progesterone to prevent spontaneous preterm births in pregnant women with cervical lengths 25 mm or less as measured by transvaginal ultrasonography.
This was a multicenter, open-label, randomized, noninferiority trial. Women with singleton pregnancies and a short cervix (25 mm or less) measured transvaginally at the second-trimester ultrasonogram were invited to participate. They were computer-randomized (one to one) into cervical pessary placement or treatment with vaginal progesterone (200 mg/24 hours). The primary outcome was spontaneous preterm delivery before 34 weeks of gestation. The noninferiority margin was set at 4% with a 0.025 one-sided α level and a statistical power of 80%. That is, if the 95% CI upper bound exceeded 4%, the pessary could not be deemed noninferior. A sample size of 254 women was required to show noninferiority of the pessary to progesterone.
The trial was conducted from August 2012 to April 2016 with the participation of 27 Spanish hospitals. A total of 254 patients were enrolled and 246 included in the intention-to-treat analysis. Demographic and baseline characteristics were similar across groups. The rate of spontaneous delivery before 34 weeks of gestation was 14% (n=18/127) in the pessary group and 14% (n=17/119) in the progesterone group with a risk difference of −0.11% (95% CI −8.85% to 8.62%; P=.99), that is, noninferiority was not shown for the pessary. The incidence of increased vaginal discharge (87% vs 71%, P=.002) and discomfort (27% vs 3%, P<.001) was significantly higher in the pessary group.
A cervical pessary was not noninferior to vaginal progesterone for preventing spontaneous birth before 34 weeks of gestation in pregnant women with short cervixes.
EU Clinical Trials Register, 2012-000241-13; ClinicalTrials.gov, NCT01643980.
Cervical pessary was not noninferior to vaginal progesterone for preventing spontaneous birth before 34 weeks of gestation in pregnant women with short cervixes.
Maternal-Fetal Medicine Unit, Department of Obstetrics, and the Clinical Pharmacology Service, University Hospital Puerta de Hierro Majadahonda, and the Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital Fundación Alcorcón, Madrid, the Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital Miguel Servet, Zaragoza, the Maternal-Fetal Medicine Unit, Department of Obstetrics, Complejo Asistencial León, León, the Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital Burgos, Burgos, the Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital Infanta Elena, Valdemoro, and the Maternal-Fetal Medicine Unit, Department of Obstetrics, Hospital de Fuenlabrada, Madrid, Spain.
Corresponding author: Sara Cruz-Melguizo, MD, Servicio de Ginecología y Obstetricia, Hospital Universitario Puerta de Hierro Majadahonda, c/Manuel de Falla 1, 28222, Madrid, Spain; email: email@example.com.
This study was fully funded with public funds obtained in competitive calls: grant EC11/086 of the Ministry of Health Call for Independent Clinical Research in year 2011 and grant PI12/02240 from the Institute of Health Carlos III. The study was performed and monitored with the support of the Spanish Clinical Research Network, funded by grant PT13/0002/0005 from the National R+D+I 2013-2016 Plan of the Institute of Health Carlos III (AES 2013).
Financial Disclosure The authors did not report any potential conflicts of interest.
Presented at the 16th World Congress in Fetal Medicine, June 25–27, 2017, Ljubljana, Slovenia.
* For a list of members in the PESAPRO study group, see Appendix 1 online at http://links.lww.com/AOG/B147.
The authors thank Professor Zarko Alfirevic (Liverpool Women's Hospital, Liverpool, U.K.) for his valuable comments and guidance with the editing of the manuscript. We also thank Ana Royuela for her help with the statistical analysis, Lourdes Cabrera for her enthusiasm, Paloma Rodriguez for her constant support, and all the participants who agreed to take part in the study. The authors also thank the funders of the study (Spanish Minister of Health, Institute Carlos III and the Spanish Clinical Research Network); without them, this study would not have been possible.
Each author has indicated that he or she has met the journal's requirements for authorship.
Received March 27, 2018
Received in revised form June 14, 2018
Accepted June 21, 2018