Study protocol for two randomised controlled trials evaluating the effects of Cerclage in the reduction of extreme preterm birth and perinatal mortality in twin pregnancies with a short cervix or dilatation: the TWIN Cerclage studies
Ben W Mol,
Martijn A Oudijk,
Enrico Lopriore,
Judith O E H van Laar,
Yves Jacquemyn,
Eva Pajkrt,
Marjon A de Boer,
Judith Bosmans,
Isabelle Dehaene,
Sam Schoenmakers,
Jelmer R Prins,
Ruben Duijnhoven,
Jan B Derks,
Wilfried Gyselaers,
Caroline Van Holsbeke,
Salwan Al-Nasiry,
Joris van Drongelen,
Lissa van Gils,
Margo Lutke Holzik,
Marieke H Knol,
Liesbeth Lewi,
Hannes van der Merwe,
Sylvia A Obermann-Borst,
Mayella Holthuis
Affiliations
Ben W Mol
department of obstetrics and gynaecology, school of medicine, Monash University, Melbourne, Victoria, Australia
Martijn A Oudijk
Department of Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam, The Netherlands
Enrico Lopriore
Department of Neonatology and Fetal Medicine, Leiden University Medical Center, Leiden, The Netherlands
Judith O E H van Laar
Department of Obstetrics & Gynaecology, Máxima Medical Center, Veldhoven, The Netherlands
Yves Jacquemyn
University Hospital Antwerp, Antwerpen, Belgium
Eva Pajkrt
Department of Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam, The Netherlands
Marjon A de Boer
Department of Obstetrics and Gynecology, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Judith Bosmans
Department of Health Sciences, Amsterdam UMC Location AMC, Amsterdam, Noord-Holland, The Netherlands
Isabelle Dehaene
University Hospital Ghent, Gent, Belgium
Sam Schoenmakers
Department of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, The Netherlands
Jelmer R Prins
Department of Obstetrics and Gynaecology, University Medical Center Groningen, Groningen, The Netherlands
Ruben Duijnhoven
Department of Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam, The Netherlands
Jan B Derks
Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands
Wilfried Gyselaers
Department of Obstetrics and Gynecology, Hospital Oost-Limburg, Genk, Belgium
Caroline Van Holsbeke
AZ Sint-Lucas Brugge, Brugge, West-Vlaanderen, Belgium
Salwan Al-Nasiry
Department of Obstetrics and Gynaecology, Maastricht UMC+, Maastricht, The Netherlands
Joris van Drongelen
Department of Obstetrics and Gynecology, Radboud Universiteit, Nijmegen, The Netherlands
Lissa van Gils
Department of Obstetrics and Gynaecology, Amsterdam UMC, Amsterdam, The Netherlands
Margo Lutke Holzik
Department of Obstetrics and Gynecology, Leiden Universitair Medisch Centrum, Leiden, The Netherlands
Marieke H Knol
Department of Obstetrics and Gynaecology, Isala Zwolle, Zwolle, The Netherlands
Liesbeth Lewi
Fetal Medicine Unit, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
Hannes van der Merwe
Fetal Medicine Unit, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
Sylvia A Obermann-Borst
Care4Neo, Neonatal patient and parent advocacy organization, Rotterdam, The Netherlands
Mayella Holthuis
Patient organization `Extreme Vroeggeboorte`, Amsterdam, The Netherlands
Introduction Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage.Methods and analysis We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective.Ethics and dissemination This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.Trial registration number ClinicalTrials.gov, NCT05968794.
