Effect of History-indicated Early Treatment With Cervical Pessary Versus Expectant Management Treatment With Rescue Cerclage in Cases With Cervical Shortening in Singleton Pregnancies at High-risk for sPTB on Children's Long-term Outcome
Phase: NA
Conditions: Preterm Birth, Premature Birth
Sponsor: Bürgerhospital Frankfurt

 
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Code: PROMETHEUS-Trial 
 
 
Version 1.3 (January 2018) 
 
 
 
 
 
Effect of  
history-indicated early treatment with Arabin cervical pessary  
versus  
expectant management treatment with rescue cerclage placement in cases with cervical shortening  
in singleton pregnancies at high-risk for preterm birth on childern’s long-term survival  
without neurodevelopmental disability 
THE PROSPECTIVE RANDOMIZED PROMETHEUS-TRIAL 

 
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Summary 
 
 
Description: Clinical Trial with a sanitary device in its authorized using conditions. 
 
Title: Effect of history-indicated early treatment with Arabin cervical pessary 
versus expectant management treatment with rescue cerclage placement in 
cases with cervical shortening in singleton pregnancies at high-risk for 
preterm birth on childern’s long-term survival without neurodevelopmental 
disability 
The Prometheus-Trial 
 
Sponsor:  Bürgerhospital und Clementine Kinderhospital gGmbH, Frankfurt/M., 
Germany 
 
Coordinator of the study: PD Dr. med. Ioannis Kyvernitakis (Frankfurt/M., Germany) 
 
Main investigator of the study (Frankfurt/M.): PD Dr. med. Ioannis Kyvernitakis  
 
Scientific assistance: Marita Wasenitz 
Statistical support and power analysis: Univ.-Prof. Dr. Eva Herrmann, Faculty of 
Biostatistics, Goethe-University of Frankfurt 
Scientific expert support for neurodevelopmental questionnaires: PD Dr. med. Heike 
Philippi, Faculty of Medicine, University of Heidelberg 
 
Study Centres & Site investigators: 
  
International Centres 
• 
University of Adelaide, Australia 
Professor Ben Willem Mol, MD, PhD 
• 
Medical School of the Aristotle-University of Thessaloniki, Greece 
Professor Apostolos Athanasiadis, MD, PhD 
• 
University Hospital of Athens, Greece 
Professor George Daskalakis, MD, PhD 
• 
Vall d'Hebron University Hospital, Spain 
Professor Elena Carerras, MD, PhD  
  
German Centres 
• 
Vivantes Klinikum im Friedrichshain, Berlin, Germany 
Associate Professor Lars Hellmeyer, MD, PhD 
• 
Bürgerhospital Frankfurt, Germany 
Associate Professor Ioannis, Kyvernitakis, MD, PhD 
• 
Universitätsklinikum Frankfurt, Germany  
Professor Frank Louwen,MD, PhD, PhD h.c. so korrekt? 
• 
Asklepios Kliniken, Hamburg, Germany 
Associate Professor Holger Maul, MD, PhD 
• 
Universitätsklinikum des Saarlandes, Homburg, Germany 
Amr Hamza, MD, PhD 
• 
Charite-Universitätsmedizin Berlin 
Jens H. Stupin, MD, PhD  

 
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Reference 
Ethics 
Committee: Ethik-Kommission 
Landesärztekammer 
Hessen, 
Frankfurt/M., Germany 
 
Scientific Expert Panel at Bürgerhospital Frankfurt/M. 
 
• 
PD Dr. med. Dr. med. habil. Franz Bahlmann 
Head of the Department of Obstetrics and Gynecology 
Tel.: +4969 1500 412 / Fax +4969 1500 400  
f.bahlmann@buergerhospital-ffm.de 
 
Monitoring Data Committee:  
• 
Scientific Data Monitoring Committee 
Prof. Dr. med. Ben Willem Mol 
Full Professor of Obstetrics and Gynaecology, Robinson Research Institute, 
SAHMRI, University of Adelaide, Australia 
ben.mol@adelaide.edu.au. 
 
Scientific Advisory Board 
• 
Prof. Dr. Zarko Alfirevic 
Full Professor of Obstetrics and Gynecology 
Department of Women`s and Children´s Health, University of Liverpool, UK 
zarko@liv.ac.uk  
 
Sanitary device: The Arabin cervical pessary, which is CE-certified for preventing SPB 
(CE 0482 / EN ISO 13485: 2012 + AC:2012 annex III of the council directive 93/42 
EEC).  
 
Main objective: To assess the impact of a prophylactic treatment with a cervical 
pessary in women at high risk of spontaneous Preterm Birth (PTB) due to a history of 
previous preterm deliveries and/or a history of previous cervical surgery (conisation) 
on the children´s survival without neurodevelopmental disability at the age of 3. 
Recruitment will be offered to all women at 12+0 -16+0 weeks of gestation with 
status after PTB in previous pregnancies and/or conisation. 
 
Study 
design: 
Prospective 
Open-label 
Multicentre 
International 
Collaborative 
Randomized Controlled Trial, in parallel groups, based on intention to treat comparing 
the early placement of a cervical pessary with standard care management in cases of a 
singleton pregnancies at high-risk for PTB. The standard care arm (control group) shall 
receive a rescue cerclage in cases with cervical shortening. Therefore, serial cervical 
length measurements should be conducted onward the 12+0 week every 4 weeks.  
 
Main outcome: Children´s survival without neurodevelopmental disability at 3 years of 
age. 
 
Study population: The study will be proposed to women with a singleton pregnancy at 
12+0 – 16+0 weeks of gestation and a history of at least one previous preterm 
delivery and/or a history of previous cervical surgery attending the reference hospital 
and who do not fulfil the exclusion criteria. In this context, cases with previous 
preterm birth should only be considered, when birth occurred before the 34+0 week 
of pregnancy. 
The patients will be informed of the intended therapeutic effect and possible side 
effects. If they agree and after obtaining their informed consent, they will be 
randomised according to either cervical pessary placement up to 37+0 weeks (= 
pessary group) or expectant management according to standard care and a 

 
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McDonald cerclage placement as soon as a cervical shortening below 25 mm is 
diagnosed (=control arm). 
Hereby, patients of the control arm shall receive serial cervical length measurements 
by transvaginal ultrasound (TVS) every 4 weeks started at 12+0 weeks.  
A cerclage may be indicated when the cervical length is below 25 mm.1 (s. consort-
diagram). 
 
Sample size:  
For sample size calculation, we assume a combined event rate for the primary 
outcome (long-term survival without neurodevelopmental disability at 3 years of 
follow up) of 8% for the pessary group and an event rate of 20% for the control group 
van’t Hooft 2016. Group sample size of 121 in both groups achieve 80% power to detect 
this difference using a two-sided chi-square test with significance level alpha=5%. To 
account for a dropp out rate around 25%, sample size of 155 in each group, overall 
n=310 women will be recruited. 
 
Study calendar:  
Starting recruitment: June, 1st, 2018 
Finishing recruitment and follow-up: est. June 1st, 2023. 
Final report: Sept. 1st, 2023. 
 
 
Table of contents 
 
1. General Information 
 
1.1. Title, protocol identifying number and date. 
1.2. Name and address of the Sponsor. 
1.3. Name and title of the authorized person by the Sponsor to sign the protocol and 
the protocol amendments. 
1.4. Name, title, addresses and telephone numbers of the medical experts of the 
Sponsor of the trial. 
1.5. Name and title of all the researchers who are responsible for conducting the trial 
and address and telephone numbers of trial sites. 
1.6. Name, title, address and telephone number of the qualified physician who is 
responsible for all medical decisions on each trial site. 
1.7. Name and address of the medical departments or institutions that are involved in 
the trial. 
 
2. Rationale 
 
2.1. Justification of the relevance of the trial. 
2.2. Description of the study population. 
2.3. Name and description of the device under investigation. 
2.4. Statement that testing will be performed according to the protocol, GCP and 
applicable legal requirements. 
 
3. Objective 
 
4. Design 
 
4.1. Specific description of primary and secondary variables. 
4.1.1. Primary outcome. 
4.1.2. Secondary outcomes. 
4.2. Description of the trial design. 

 
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4.3. Flowchart. 
4.4. Description of the medical device and treatment regimen. 
4.5. Expected duration of subject’s participation. 
4.6. Completion and interruption criteria of the study or the subjects. 
4.7. Maintenance of the randomization codes and test procedures of the trial. 
4.8. Identification of data to be collected in the case report file (CRF) that should be 
considered as data source. 
4.9. Definition of what is considered to be the end of the study. 
 
5. Selection and withdrawal of subjects 
 
5.1. Inclusion criteria. 
5.2. Exclusion criteria. 
5.3. Withdrawal criteria. 
5.4. Rescue treatment criteria. 
 
6. Treatment of Subjects 
 
6.1. Treatments to be administered. 
 
7. Efficacy assessment 
 
7.1. Specification of efficacy parameters: Primary and secondary endpoints. 
7.2. Methods and timing to assess, record and analyse the efficacy parameters. 
 
8. Assessment of Safety 
 
8.1. Procedures to record and report adverse events. 
8.2. Definitions. 
8.3. Procedures for immediate notification of serious or unexpected adverse events. 
 
9. Statistics 
 
9.1. Description of statistical methods. 
9.2. Expected number of subjects to be included. 
9.3. Criteria for termination of the trial. 
9.4. Selection of subjects to be included in each analysis. 
 
10. Direct Access to Data Source 
 
11. Quality and Control Assurance 
 
12. Ethical issues 
 
13. Data Management and Registry file 
 
14. Funds and Insurance 
 
15. Publication Policy 
 
16. Legal Issues 
 
17. References 
 
18. Annex 

 
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1. General information 
 
1.1. Title, protocol identifying number and date. 
 
Effect of history-indicated early treatment with Arabin cervical pessary versus 
expectant management standard care treatment with cerclage placement only 
in cases with cervical shortening in singleton pregnancies at high-risk for 
preterm birth on childern’s long-term survival without neurodevelopmental 
disability 
The Prometheus-Trial 
Code: The Prometeus-Trial 
Version and date: version 1.3 (Jan. 19, 2018) 
 
1.2. Name and address of the Sponsor. 
 
Bürgerhospital und Clementine Kinderhospital Frankfurt gGmbH  
CEO Wolfgang Heyl 
Nibelungenallee 37-41, 60318 Frankfurt am Main 
 
1.3. Name and title of the authorised person by the Sponsor to sign the protocol 
and the protocol amendments. 
 
PD Dr. med. Ioannis Kyvernitakis 
Consultant at Department of Obstetrics and Gynecology 
Bürgerhospital, and Clementine Kinderhospital gGmbH Frankfurt/M., Germany 
 
1.4. Name, title, addresses and telephone numbers of the medical experts of the 
Sponsor of the trial.  
 
o PD Dr. med. Dr. med. habil. Franz Bahlmann 
Head of the Department of Obstetrics and Gynecology 
Tel.: +4969 1500 412 / Fax +4969 1500 400  
Email: f.bahlmann@buergerhospital-ffm.de 
 
o PD Dr. med. Ioannis Kyvernitakis 
Consultant at Department of Obstetrics and Gynecology 
Tel: +4969 1500 5807 / Fax +4969 1500 400 
Email: i.kyvernitakis@buergerhospital-ffm.de, janniskyvernitakis@gmail.com 
 
Bürgerhospital Frankfurt/M.  
Nibelungenallee 37-41 
60318 Frankfurt am Main, Germany 
 
 
1.5. Name and title of all the researchers who are responsible for conducting the 
trial and address and telephone numbers of the trial sites.  
 
PD Dr Franz Bahlmann. Head of Obstetrics Department. 
PD Dr. Ioannis Kyvernitakis. Consultant at Obstetrics Department. 
 

 
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Bürgerhospital Frankfurt/M.  
Nibelungenallee 37-41 
60318 Frankfurt am Main, Germany 
Tel: +49 69 1500 412 / Fax +49 69 1500 4000 
 
Other centres that will participate on the trial: 
 
International Centres 
o University of Adelaide, Australia 
Professor Ben Willem Mol, MD, PhD 
Tel.: +61 4 3412 2170 
ben.mol@adelaide.edu.au 
o Medical School of the Aristotle-University of Thessaloniki, Greece 
Professor Apostolos Athanasiadis, MD, PhD 
Department of Obstetrics and maternal fetal medicine 
Tel: +30 6944 315785 
apostolos3435@gmail.com 
o University Hospital of Athens, Greece 
Professor George Daskalakis, MD, PhD 
Department of Obstetrics and Gynecology 
Tel.: +30 694 5235757 
gdaskalakis@yahoo.com 
o Vall d'Hebron University Hospital, Spain 
Professor Elena Carerras, MD, PhD  
Department of Obstetrics and Gynecology 
ecarreras@vhebron.net  
Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron 119-129,  
08035 Barcelona 
Tel.:+34 934 89 30 00 
  
German Centres 
o Vivantes Klinikum im Friedrichshain, Berlin 
Associate Professor Lars Hellmeyer, MD, PhD 
Head of Department of Obstetrics and Gynecology  
Email: Lars.Hellmeyer@vivantes.de  
Vivantes Klinikum im Friedrichshain, Landsberger Allee 49, 10249 Berlin,  
Tel.: +49 30 130 23 1442 
o Universitätsklinikum Frankfurt  
Professor Frank Louwen,MD, PhD, PhD h.c. 
Head of Department of Obstetrics and Perinatology 
Mail: Louwen@em.uni-frankfurt.de  
Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7 
60590 Frankfurt am Main 
Tel: +49 69 6301 7703 
o Asklepios Kliniken, Hamburg 
Associate Professor Holger Maul, MD, PhD 
Head of Department of Obstetrics and Gynecology  
Mail: h.maul@asklepios.com 
Asklepios Krankenhaus Barmbek, 22087 Hamburg 
Tel: +49 40 2546 662 
o Universitätsklinikum des Saarlandes, Homburg 
Amr Hamza, MD, PhD 
Senior Consultant of Department of Obstetrics and Gynecology  

 
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Mail: amr.hamza@uks.eu  
Universitätsklinikum des Saarlandes, Kirrbergerstr. 100, 66424 Homburg 
Tel: +49 6841 16 28000 
o Charite-Universitätsmedizin Berlin 
Jens H. Stupin, MD, PhD  
Department of Obstetrics and Gynecology 
jens.stupin@charite.de  
Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin  
Tel: +49 30 450 – 50 
 
 
1.6. Name, title, address and telephone number of the qualified physician who is 
responsible for all medical decisions on each trial site. 
 
International Centres 
o Professor Ben Willem Mol, MD, PhD 
Tel.: +61 4 3412 2170 
ben.mol@adelaide.edu.au 
University of Adelaide, Australia 
o Professor Apostolos Athanasiadis, MD, PhD 
Tel: +30 6944 315785 
apostolos3435@gmail.com  
Medical School of the Aristotle-University of Thessaloniki, Greece 
Department of Obstetrics and maternal fetal medicine 
o Professor George Daskalakis, MD, PhD 
Tel.: +30 694 5235757 
gdaskalakis@yahoo.com 
University Hospital of Athens, Greece  
Department of Obstetrics and Gynecology 
o Professor Elena Carerras, MD, PhD  
Tel.:+34 934 89 30 00 
ecarreras@vhebron.net  
Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron 119-129,  
08035 Barcelona 
Department of Obstetrics and Gynecology 
 
German Centres 
o Associate Professor Lars Hellmeyer, MD, PhD 
Tel.: +49 30 130 23 1442 
Email: Lars.Hellmeyer@vivantes.de  
Vivantes Klinikum im Friedrichshain, Landsberger Allee 49, 10249 Berlin 
Head of Department of Obstetrics and Gynecology  
o Associate Professor Ioannis, Kyvernitakis, MD, PhD 
Mail: I.Kyvernitakis@buergerhospital-ffm.de 
Tel: +49 69 1500 5807 
Bürgerhospital Frankfurt/M, Nibelungenallee 37-41, 60318 Frankfurt am Main 
Consultant at Department of Obstetrics and Gynecology 
o Professor Frank Louwen,MD, PhD, PhD h.c.  
Tel: +49 69 6301 7703 
Mail: Louwen@em.uni-frankfurt.de  
Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7 
60590 Frankfurt am Main 
Head of Department of Obstetrics and Perinatology 

 
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o Associate Professor Holger Maul, MD, PhD 
Tel: +49 40 2546 662 
Mail: h.maul@asklepios.com 
Asklepios Krankenhaus Barmbek, 22087 Hamburg, 
Head of Department of Obstetrics and Gynecology  
o Universitätsklinikum des Saarlandes, Homburg 
Amr Hamza, MD, PhD 
Tel: +49 6841 16 28000 
Mail: amr.hamza@uks.eu 
Universitätsklinikum des Saarlandes, Kirrbergerstr. 100, 66424 Homburg 
Senior Consultant of Department of Obstetrics and Gynecology  
o Jens H. Stupin, MD, PhD  
Tel: +49 30 450 – 50 
jens.stupin@charite.de  
Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin  
Department of Obstetrics and Gynecology 
 
 
1.7. Name and address of the medical departments or institutions that are 
involved in the trial.  
 
Department of Obstetrics and Gynecology international Centres: 
o University of Adelaide, Adelaide, Australia 
o Medical School of the Aristotle-University of Thessaloniki, Thessaloniki, 
Greece 
o University Hospital of Athens, Athens, Greece  
o Vall d'Hebron University Hospital, Barcelona, Spain 
 
Department of Obstetrics and Gynecology in Germany: 
o Bürgerhospital Frankfurt/M, Nibelungenallee 37-41, 60318 Frankfurt am Main. 
o Kath. Marien Krankenhaus GmbH, Alfredstr. 9, 22087 Hamburg. 
o Vivantes Klinikum im Friedrichshain, Landsberger Allee 49, 10249 Berlin. 
o Universitätsklinikum des Saarlandes, Kirrbergerstr. 100, 66424 Homburg.  
o Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin  
o Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main 
 
 
2. Rationale 
 
2.1. Justification of the relevance of the trial. 
 
Preterm birth complicates 13% of all pregnancies worldwide and is the most 
important cause of neonatal morbidity and mortality.2 Although disability-free survival 
rates have increased over the years as a result of improved facilities and treatments, 
preterm birth is still accountable for 75% of all perinatal deaths and >50% of 
morbidities.3,4  
Women with a history of a preterm delivery have a distinctly increased risk to deliver 
preterm in a subsequent pregnancy. This risk ranges from 17,2% with one previous 
preterm delivery up to 28% for two previous preterm deliveries.5 This also applies to 
women with a history of a second trimester fetal-loss after 20 weeks of gestation who 
show an increased risk of 12% for preterm birth in a subsequent pregnancy.6 Yet 
another independent risk factor for PTB is a previous cervical surgery; after a single 
surgical conisation the risk of PTB increases almost 5 fold and after two even10-
fold.7 

 
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Evidence based treatment guidelines for these high-risk pregnancies are not 
available in Germany, expectant management is the usual care for these patients.   
The European Association of Perinatal Medicine8 and the Society for Maternal-Fetal 
Medicine Publications Committee (SMFM) 9 recommends for the US 17-alpha 
hydroxyprogesterone caproate (17-OHPC) therapy for women with a history of PTB 
in a subsequent singleton pregnancy. But this is not a treatment option for the 
majority of European countries as the drug is only available in some EC-countries on 
basis of old regime accreditations. The SMFM-statement details that vaginal 
progesterone should not be considered a substitute for 17-OHPC, whereas the 
European guideline does not differentiate between 17-OHPC and vaginal 
progesterone.  
Up to now the risk factor previous PTB has only been investigated in RCTs for 17-
OHCP 10, 11, 12, 13 or in RCTs where the risk factor previous PTB was combined with 
the risk factor cervical shortening (vaginal progesterone 14, 15; cerclage 16, 17-OHP 1).  
Looking at the evidence of therapeutic effectiveness of vaginal progesterone these 
risk factors should be addressed separately. Vaginal progesterone proved to be 
ineffective in the prevention of recurrent PTB 14, 15 but effectively reduced PTB in 
women with a short cervix 17, 18 .  
For cervical pessary therapy there is up to now only one cohort analysis 19  for the 
combined risk factors available proving the placement of a cervical pessary to be as 
effective as cerclage or treatment with 200 mg vaginal progesterone in reducing 
preterm birth rate.  
The risk factor ‘history of at least one cold knife conisation’ for PTB was up to now 
only addressed in a pilot study investigating the effect of pessary treatment in 
asymptomatic women with a singleton pregnancy along with a short sonographic 
cervix and it suggested a beneficial effect on the prolongation of the pregnancy 7.  
A cervical pessary to support the cervix in pregnant women with cervical insufficiency 
was introduced in 1960. It is a silicone ring with a smaller diameter to be fitted around 
the cervix and a larger diameter to fix the device against the pelvic floor. This 
effectively rotates the cervix toward the posterior vaginal wall and corrects the 
cervical angle 20. 
In approximately 1/3 21 of pregnancies leading to PTB cervical shortening develops. 
Here the placement of a cervical pessary is a good therapeutic option. For this risk 
factor good evidence is available for cervical pessary treatment in singleton 22 and 
twin pregnancies 23, 24. A Cochrane review 25 detailed a significant decrease in the 
incidence of spontaneous PTB in women with a short cervix when compared with 
expectant management: PTB less than 37 weeks’ gestation (22% versus 59 %; RR 
0.36, 95% CI 0.27 to 0.49) and PTB less than 34 weeks´ gestation (6% and 27% 
resp. RR 0.24; 95% CI 0.13 to 0.43). 
 
This is the first RCT aiming to investigate the impact of a preventive cervical pessary 
therapy for the prevention of recurrent PTB in women with a history of PTB and/or 
history of at least one conisation.  
Furthermore this RCT is a part of the first worldwide prospective metaanalysis in the 
medicine Global Obstetrics Network http://www.globalobstetricsnetwork.org/projects/ 
The primary outcome “Children´s survival without neurodevelopmental disability at 
the age of 3 years” measures the long-time outcome of the intervention according to 
the CROWN 26 criteria. 
Cervical pessary treatment is a non-invasive, well-tolerated and cost-effective 
treatment option 20 which could be easily implemented in daily practice if it proves to 
have a preventive effect of PTB. This especially applies for developing countries, 
where for example serial cervix length measurements to detect cervical shortening 
are not feasible.  
 

 
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2.2. Description of the study population. 
 
Women with a singleton pregnancy at 12 – 16 weeks of gestation and a history of at 
least one previous preterm delivery before 34+0 weeks and/or a history of previous 
cervical surgery attending the reference hospital and who do not fulfil the exclusion 
criteria the study will be proposed. The patients will be informed of the intended 
therapeutic effect and possible side effects. If they agree and after obtaining their 
informed consent, they will be randomised according to either usual management 
with rescue cerclage placement only when (and as soon as possible) a cervical 
shortening below 25 mm occurs (=control group) or cervical pessary placement (= 
pessary group).  
Pessaries or cerclage shall be placed up to 37+0 weeks of gestation. In the control 
group serial cervical length measurements shall be conducted every 4 weeks in order 
to diagnose cervical shortening as soon as possible. 
2.3. Name and description of the device under investigation.  
 
The Arabin cervical pessary, which is CE-certified for preventing SPB (CE 0482 / EN 
ISO 13485: 2012 + AC:2012 annex III of the council directive 93/42 EEC). 
See annex I. 
2.4. Statement that testing will be performed according to protocol, GCP and 
applicable legal requirements. 
 
The Clinical Trial will be conducted following the protocol, the GCP, and all legal 
requirements. 
 
 
3. Objective 
 
This study aims to investigate the benefit of a prophylactic cervical pessary treatment  
in women at high risk of PTB due to a history of at least one previous preterm 
delivery before 34+0 weeks and/or a history of previous cervical surgery on the 
children´s long-term survival without neurodevelopmental disability. 
Hereby, a standardized and validated test called ‘Ages and Stages 3rd edition’27 
should evaluate the children’s neurodevelopment. The test should be conducted by 
the parents and takes approximately 12 minutes. The questionnaires will be provided 
by the sponsor. 
 
 
4. Design 
 
4.1. Specific description of primary and secondary variables. 
 
4.1.1. Primary outcome: 
 
o Children`s long-term survival without neurodevelopmental disability 
 
4.1.2. Secondary outcomes:  
o Offspring 
• 
Time to birth 
• 
Preterm birth before 37 weeks: rate of delivery before 36+6 weeks  
• 
Preterm birth before 34 weeks: rate of delivery before 33+6 weeks  

 
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• 
Preterm birth before 32 weeks: rate of delivery before 31+6 weeks  
• 
Preterm birth before 30 weeks: rate of delivery before 29+6 weeks  
• 
Preterm birth before 28 weeks: rate of delivery before 27+6 weeks  
• 
Birth weight: median weight (g) of the newborns at birth 
• 
Fetal or neonatal death: rate of intrauterine demise or neonatal death 
during the first 24 hours 
• 
Neonatal morbidity: rate of major adverse neonatal outcomes before 
discharge from the hospital 
▪ 
Intraventricular Haemorrhage (IVH): grades III-IV 
▪ 
Retinopathy of prematurity 
▪ 
Respiratory Distress Syndrome (RDS): grades II-IV, 
▪ 
Need for ventilation > 72 h 
▪ 
Necrotising enterocolitis 
▪ 
Proven or suspected sepsis, antibiotics (>5 days) 
▪ 
Need (Duration in days) for neonatal special care (NICU)  
• 
Harm from intervention  
 
o Mother: 
• 
Maternal death 
• 
Significant maternal adverse events (rate): 
▪ 
Heavy bleeding: bleeding that requires a medical intervention 
▪ 
Cervical tear: cervical rupture due to the pessary placement 
▪ 
Uterine rupture: rupture of the uterus due to contractions or 
surgery 
• 
Physical or psychological intolerance to pessary: discomfort or pain due to 
the pessary that makes daily life uncomfortable (number of cases) 
• 
Rupture of membranes before 32 weeks: rate of rupture of amniotic 
membranes before 31+6 weeks 
• 
Infection/inflammation  
• 
Hospitalisation for threatened preterm labour before 32 weeks: 
requirement of hospitalisation due to preterm contractions that need 
medical treatment to try to stop them before 31+6 weeks (rate) 
▪ 
Mean hospital stay duration: number of days of admittance at the 
hospital 
▪ 
Use of tocolytic treatment: Type of tocolytic, days of treatment, 
dose 
 
4.2. Description of the trial design. 
 
Open Multicentre International Collaborative Randomized Controlled Trial, in parallel 
groups, based on intention-to-treat analysis comparing the placement of a prophylactic 
cervical pessary with usual management in singleton pregnancies at high-risk of PTB 
due to a history of at least one previous preterm delivery before 34+0 weeks and/or a 
history of previous cervical surgery.  
 
 
4.3. Flowchart. 

 
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4.4. Description of the medical device and the treatment regimen. 
 
The cervical pessary is a vaginal device (silicone ring) that is used to treat pregnant 
women for preventing spontaneous preterm birth. This device can be easily placed 
around the uterine cervix without pain (see annex I). 

 
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Women with a singleton pregnancy at 12+0 – 16+0 weeks of gestation and a history 
of at least one previous preterm delivery before 34+0 weeks and/or a history of 
previous cervical surgery attending the reference hospital for a preventive 
examination will be informed of the ongoing trial. The patient will be advised of the 
intended therapeutic effect and possible side effects. If they agree and after obtaining 
their informed consent, they will be randomised according to either usual 
management (=control group) or cervical pessary placement up to 37+0 weeks (= 
pessary group).  
If the pregnant woman is assigned to the pessary group and after having excluded a 
vaginal infection the pessary will be inserted directly. This procedure does not need 
anaesthesia and it does not need to be done in a surgery room. After the insertion of 
the pessary the correct fit of the pessary is verified by transvaginal ultrasound and in 
case it does not fit perfectly, it can easily be adjusted.  
In the control-group the cervical length of the women will be evaluated by 
transvaginal ultrasound scan started from randomization and every 4 weeks; if a 
cervical shortening below 25mm is detected a Mc Donald cerclage will be placed. 
The pessary will be removed at 37+0 weeks of gestation, or before if any unexpected 
event occurs (see 4.6). After insertion of the pessary the obstetrical management 
during the remainder of the pregnancy will be usual management. 
Further surveillance of the pregnancy will not be influenced by the participation on 
the study. 
 
 
 4.5. Expected duration of subject’s participation. 
 
Starting recruitment: June, 1st, 2018 
Finishing recruitment and follow-up: est. June 1st, 2023. 
Final report: Sept. 1st, 2023 
 
4.6. Completion and interruption criteria of the study or the subjects. 
 
The pessary will be removed at 37+0 weeks of pregnancy. The indications to remove 
them before this time will be: active bleeding stronger than period bleeding, 
persistent contractions after tocolysis and premature rupture of the membranes after 
34+0 weeks. 
After removing the pessary, the obstetrical management will be done as usual and 
will not be influenced by the study. 
 
4.7. Maintenance of the randomisation codes and test procedures of the trial. 
 
Every participating centre will have its own randomisation list.  
We have created a database in a website so it can be accessed worldwide, that 
every hospital will be able to randomize their patients.  
Every center will receive a password and a username in order to access the 
database for recruitment, randomization and documentation of patient data. Hereby, 
a personal identification number will be assigned for every patient. Patient names will 
not appear in the databases.  
This database will be supervised and coordinated by PD Dr. Ioannis Kyvernitakis, 
Bürgerhospital Frankfurt/M. (Webmaster). 
 
4.8. Identification of data to be collected in the case report files (CRF) that 
should be considered as data source. 
 
Data will be collected in E-CRF, provided by >Dr. Olaf Hars Wissenschaft, Berlin< on 
study software “Castor”. 

 
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4.9. Definition of what is considered to be the end of the study. 
 
The study will be finished after the 3 year-follow up examination of the surviving 
children focusing on neurodevelopmental disabilities.  
 
 
5. Selection and withdrawal of subjects 
5.1. Inclusion criteria. 
 
o Women with a singleton pregnancy and a history of at least one previous preterm 
delivery before 34+0 weeks and/or a history of previous cervical surgery 
o 12+0 -16+0 weeks of gestation 
o Minimal age of 18 years 
o Informed consent signature 
5.2. Exclusion criteria. 
 
o Major fetal abnormalities (requiring surgery or leading to infant death or severe 
handicap) 
o Cerclage prior to randomisation 
o Uterine malformation 
o Placenta previa totalis 
o Active vaginal bleeding at the moment of randomization 
o Spontaneous rupture of membranes at the time of randomization 
o Silicone allergy 
o Painful regular uterine contractions 
o Current participation in another RCT 
 
5.3. Withdrawal criteria. 
 
If a participant may voluntarily withdraw from treatment or if it is necessary to remove 
the pessary due to the conditions described before, the patients will be followed as 
usual until delivery (intention-to-treat analysis).  
Replacement of patients is not applicable in this trial. 
 
5.4. Rescue treatment criteria.  
 
Regarding the control group, a McDonald cerclage may be indicated if there is a 
cervical shortening below 25 mm during the follow-up scans according to the current 
guidelines and expert recommendations11.  
 
 
6. Treatment of Subjects 
6.1. Treatments to be administered. 
 
The pessary will be inserted during a preventive examination in pregnancy in the 
examination room. This procedure does not need anaesthesia and it does not need 
to be done in a surgery room. After the insertion of the pessary the correct fit of the 
pessary is verified by transvaginal ultrasound and in case it does not fit perfectly, it 
can easily be adjusted. In the control-group the cervical length of the women will be 
evaluated by transvaginal ultrasound scan: if a cervical shortening below 25 mm is 

 
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detected a cervical cerclage will be placed. The pessary or cerclage will be removed 
at 37+0 weeks of gestation, or before if any unexpected event occurs (see 4.6).  
After insertion of the pessary the obstetrical management during the pregnancy will 
be usual management.  
Further surveillance of the pregnancy will not be influenced by the participation on 
the study. 
 
 
7. Efficacy assessment 
 
7.1. Specification of efficacy parameters: Primary and secondary endpoints. 
 
This study aims to investigate the benefit of a prophylactic cervical pessary treatment  
in women at high risk of PTB due to a history of at last one previous preterm delivery 
before 34+0 weeks and/or a history of previous cervical surgery on the perinatal 
outcome and on the children´s long-term survival without neurodevelopmental 
disability. 
The effect of the pessary treatment will be assessed in women independent of the 
cervical length at 12 -16 weeks of gestation compared to standard care treatment. 
 
 
7.2. Methods and timing to assess records and analyze the efficacy 
parameters. 
 
The pregnant women will be assessed according to usual obstetrical management in 
a high-risk pregnancy. 
 
 
Regular 
Preventive Exam 
 
Serial CL 
measurements 
after 
randomization 
Regular 
Preventive 
Exam 
37 WoG 
Postnatal 
evaluation 
3 years 
follow up 
(corrected 
age) 
 
Study procedure 
study inclusion 
12+0-16+0 WoG 
 
 
 
 
Informed consent  
x 
 
 
 
 
randomisation 
x 
 
 
 
 
Control-group 
 
x 
 
 
 
Pessary/cerclage 
placement 
Pessary-Group: 
Pessary at 
enrollment 
Control-Group: 
Cerclage when 
CL <25mm  
 
 
 
Pessary/cerclage 
removal 
WoG 37+0 
 
x 
 
 
physical exams 
 
 
 
 
 
Abdominal US 
x 
x 
x 
 
 
Vaginal US 
 
x 
 
 
 
pH-Value 
pH < 4,4 
pH < 4,4 
 
 
 
Neonatal examination 
 
 
 
x 
 
Ages & Stages test  
 
 
 
 
x 
Exam at paediatrician 
 
 
 
 
x 
 
 
8. Assessment of Safety 
8.1. Procedures to record and report adverse events. 

 
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If a serious and unexpected adverse effect occurs during pessary treatment, it will be 
notified to the study Sponsor. The Department of Obstetrics and Gynecology of the 
Sponsor will fill the side effects document to notify it to the Landesärztekammer 
Hessen. 
The patient affected by the adverse effect will be followed more intensively during the 
first days and if nothing else occurs, she will return to the standard control. 
 
8.2. Definitions. 
 
Adverse Event (AE): Any untoward medical occurrence in a patient or clinical 
investigation participants administered a medicinal product, which does not necessarily 
have to have a causal relationship with this treatment (the study medication). An AE 
can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the use of the study 
medication/procedure, whether or not considered related to the study medication. 
 
Adverse Reaction (AR): All untoward and unintended responses to a medicinal product 
related to any dose. The phrase "responses to a medicinal product" means that a 
causal relationship between a study medication and an AE is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or the sponsor 
as having a reasonable suspected causal relationship to the study medication / 
procedure qualify as adverse reactions. 
 
Serious Adverse Event (SAE): A serious adverse event is any untoward medical 
occurrence that at any dose: Results in death; is life-threatening, NOTE: The term "life-
threatening" in the definition of "serious" refers to an event in which the participant was 
at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe; Requires inpatient 
hospitalization or prolongation of existing hospitalization; Results in persistent or 
significant disability/incapacity, or is a congenital anomaly/birth defect. 
 
Other important medical events: Other events that may not result in death, are not life 
threatening, or do not require hospitalization, may be considered a serious adverse 
event when, based upon appropriate medical judgment, the event may jeopardize the 
patient and may require medical or surgical intervention to prevent one of the 
outcomes listed above. 
To ensure no confusion or misunderstanding of the difference between the terms 
"serious" and "severe", which are not synonymous, the following note of clarification is 
provided: 
The term "severe" is often used to describe the intensity (severity) of a specific event 
(as in mild, moderate, or severe myocardial infarction); the event itself, however, may 
be of relatively minor medical significance (such as severe headache).  This is not the 
same as "serious," which is based on patient/event outcome or action criteria usually 
associated with events that pose a threat to a participant's life or functioning as defined 
in the bullet points above. Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
 
Serious Adverse Reaction (SAR): An adverse event (expected or unexpected) that is 
both serious and, in the opinion of the reporting investigator, believed with reasonable 
probability to be due to one of the study treatments, based on the information provided. 
 
Suspected Unexpected Serious Adverse Reaction: A serious adverse reaction, the 
nature or severity of which is not consistent with the applicable product information 

 
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(e.g. Investigator’s Brochure for an unapproved investigational product or summary of 
product characteristics for an approved product). 
 
8.3. Procedures for immediate notification of serious or unexpected adverse 
events.  
 
All AEs occurring during the study /or observed by the investigator or reported by the 
participant, whether or not attributed to study medication, will be recorded on the CRF. 
The following information will be recorded: description, date of onset and end date, 
severity, and assessment of relatedness to study medication, other suspect drug or 
device and action taken. Follow-up information should be provided as necessary.  
AEs considered related to the sanitary device, as judged by a medically qualified 
investigator, will be followed until resolution or the event is considered stable. All 
related AEs that result in a participant’s withdrawal from the study or are present at the 
end of the study, should be followed up until a satisfactory resolution occurs. 
It will be left to the investigator’s clinical judgment whether or not an AE is of sufficient 
severity to require the participant’s removal from treatment. A participant may also 
voluntarily withdraw from treatment due to what he or she perceives as an intolerable 
AE. If either of these occurs, the participant must undergo an end of study assessment 
and be given appropriate care under medical supervision until symptoms cease or the 
condition becomes stable. 
A medically qualified investigator will assess the relationship of AEs to the study 
medication. 
 
All SAEs must be reported to the main investigator. He will perform an initial check of 
the report, request any additional information, and he will notify it to the Ethics 
Committee. All SAE information will be recorded. It may be appropriate that some 
SAEs do not require immediate reporting but this must be justified. Justification might 
be determined, for example, by admission to hospital, or prolongation of 
hospitalization, where this is to be expected in the underlying disease or condition. 
All adverse events (AE) life-threatening or resulting in death will be notified within 24 
hours. All AE that are not life-threatening will be notified within 15 days. The rest of AE 
will be recorded and analyzed at the end of the study. 
 
 
9. Statistics 
9.1. Description of statistical methods. 
 
A descriptive analysis by preterm birth will be carried out calculating means and 
medians for quantitative variables and proportions for categorical variables.  
The primary statistical aim is to compare the primary combined outcome “long-term 
survival without neuro-developmental disability at 3 years follow up” between the two 
treatment groups with a two-sided chi-square test. In general, statistical comparisons 
will be two-sided and use appropriate tests according to the scale of the outcome. A 
multivariate logistic regression will be fitted to control for possible confounders. 
Relative risks and 95% confidence interval as well as adjusted odds ratios will be 
calculated for the binary outcomes. Statistical significance will be accepted in all 
cases with a p≤0.05. 
The main statistical evaluation will be performed at two time points.  
(1) The complete data set for the secondary endpoints will be available after the last 
women enrolled in this study has delivered her neonate, so the analysis of these 
outcome parameter will be done right after this event.  
(2) The primary outcome will be evaluated 3 years after the last woman enrolled in 
this study has delivered her neonate. 

 
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A descriptive analysis by preterm birth will be carried out calculating means and 
medians for quantitative variables and proportions with 95% confidence intervals for 
categorical variables. 
Additionally we will perform an explorative subgroup analysis of the study collective 
comparing the efficacy of the cervical pessary treatment in women with a normal 
cervical length at 12 -16 weeks of gestation and in women who have developed a 
cervical shortening (< 25 mm) as an additional risk factor. 
For the primary endpoint we expect to have a drop out rate of up to 25% due to the 
long follow-up time (3 years) of the study; but we do not expect to have lost data for 
the secondary endpoints because for these parameters the study has a short follow-
up time till time to birth only.  
An interim analysis shall be conducted on key safety parameters after birth of 150 
neonates: the following safety endpoints will be assessed by a one-sided test with 
alpha=1%  
• on level of the neonates:  
rate of preterm birth, time to birth, birth weight, death, neonatal morbidity, harm of 
intervention  
• and on the maternal level: 
rate of hospitalisation for threatened preterm labour < 32 weeks, rate of PRoM <32 
weeks, rate of infection / inflammation, rate of physical or psychological intolerance to 
pessary, rate of SAR/SAE, death.  
 
The trial will be terminated as negative if a disadvantage for the pessary-treatment 
can be found in one of these tests. To guarantee a high safety level the significance 
level is chosen more conservatively than in a Bonferroni correction. All analysis will 
be carried out with SPSS® version 19.0 or later (IBM Company SPSS Inc. 
Headquarters, Chicago, Illinois. USA) and R version 3.2.3 or later (R Foundation for 
Statistical Computing, Vienna, Austria). 
 
Primary Outcome 
Statistical Test 
Children`s Long-Term Survival without 
Neurodevelopmental Disability (3-Years-follow up) 
Chi-Square test 
Secondary Outcome 
Statistical Test 
Birth before 34 Weeks of Gestation 
Chi-Square test or Fisher test 
Time to Birth 
Cox regression 
Birthweight 
t-test or Wilcoxon-Mann-Whitney test 
Fetal / Neonatal Death 
Chi-Square test or Fisher test 
Neonatal Morbidity 
Chi-Square test or Fisher test 
Need for Hospitalization  
Chi-Square test or Fisher test 
Days of Hospitalzation 
t-test or Wilcoxon-Mann-Whitney test 
Maternal Adverse Events 
Chi-Square test or Fisher test 
Pessary Intolerance 
Chi-Square test or Fisher test 
Vaginal Infections 
Chi-Square test or Fisher test 
 
 
 
9.2. Expected number of subjects to be included. 
 
For sample size calculation, we assume a combined event rate for the primary 
outcome (long-term survival without neurodevelopmental disability at 3 years of 
follow up) of 8% for the pessary group (see van’t Hooft, Pro Twin Trial28) and an 
event rate of 20% for the control group. Group sample size of 121 in both groups 
achieve 80% power to detect this difference using a two-sided chi-square test with 
significance level alpha=5%. To account for a drop out rate around 15%, sample size 
of 155 in each group, overall n=310 women will be recruited. 

 
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9.3. Criteria for termination of the trial.  
 
A non-justified case of maternal death (temporary stop until complete evaluation of 
the case by an external committee). 
 
9.4. Selection of subjects to be included in each analysis.  
 
The analysis will include all the subjects that have been randomised. 
 
 
10. Direct Access to Data Source 
 
Direct access will be granted to the authorized monitor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections. 
 
 
11. Quality and Control Assurance 
 
Main investigator and collaborators: In order to ensure the Quality of the data they will 
provide instructions and training to the sites involved in the trial; review the CRF data; 
and detail of any other steps taken to ensure quality of research. 
The main investigator will sign the study protocol and the “investigator’s commitment; 
he will apply for the Ethics Committee and the Director’s approval; and he will review 
the final report of the study. 
The collaborators will assess patient’s eligibility, they will inform the patients and ask 
for the informed consent; and they will be responsible of the CRF and obtaining and 
registering all data. 
 
Monitor: he will perform regular monitoring according to ICH GCP. Data will be 
evaluated for compliance with the protocol and accuracy in relation to source 
documents. Monitors will verify that the clinical trial is conducted and data are 
generated, documented and reported in compliance with the protocol, GCP and the 
applicable and local regulatory requirements.  
 
Serious Breaches: A serious breach is defined as “A breach of GCP or the trial 
protocol which is likely to effect to a significant degree: (a) the safety or physical or 
mental integrity of the subjects of the trial; or (b) the scientific value of the trial”. All 
serious breaches will be notified to the competent Regulatory Authority according to 
applicable legislation. 
 
 
12. Ethical issues 
 
The Sponsor, participating Centres and Investigator will ensure that this study is 
conducted in accordance with the Protocol, the principles of the Declaration of 
Helsinki (see annex III), ICH Guidelines for Good Clinical Practice and in full 
conformity with relevant regulations as well as applicable national laws, the German 
Law and in accordance with regulations and guidelines applicable to clinical trials 
relating to medical devices. 
The protocol, informed consent form, participant information sheet and any 
applicable documents will be submitted to an appropriate Ethics Committee (EC) and 
Regulatory Authority for written approval. All substantial amendments to the original 
approved documents will be also sent to an appropriate Ethics Committee (EC) and 

 
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Regulatory Authority for written approval. The study will not begin until the approval 
of the EC and Director’s consent. 
 
 
13. Data Management and Registry File 
 
Patient’s participation in the study will be annotated into the medical history. 
The main investigator will perform a list with the participant’s names, ID numbers and 
codes. He also will have a file with all the information referring to the study. 
All the data will be collected in a database that will be accessed worldwide.  
The randomisation will be done on a computer basis. Once entering in the website, if 
the patient fulfils the inclusion criteria, the computer generated list will randomise the 
patient to “pessary” or “control” group. 
The excluded patients will be also collected in the database. 
Every participating centre will have its own randomisation list, and it will be 
accessible with a username and password. 
The trial staff will ensure that the participants’ anonymity is maintained. Only a 
participant ID number on the CRF and in the electronic database will identify the 
participants. All documents will be stored securely and only accessible by trial staff 
and authorized personnel. The study will comply with the Data Protection Legislation 
that requires data to be anonymized as soon as it is mandatory to do so. 
 
13.1. Data ownership 
Sponsor and participating Center have expressly agreed that any and all data collected 
and prepared in the context of the study shall be the property of the Sponsor, provided 
that participating Center shall remain the owner of its source data and may utilize such 
data as it deems appropriate without the approval, but with the reliable communication 
of Sponsor. Furthermore, Sponsor will always have access to the Study data, in terms 
of good faith and cooperation, in order to improve their own knowledge and 
information. 
 
 
14. Funds and Insurance 
 
According to German legislation and Ethical Committee decisions, it is not necessary 
to enter into an insurance contract in order to cover patients while using this medical 
device in a clinical trial. Insofar as it has been issued with the appropriate certificate 
of the State Medicines Agency to the concrete use of the medical device. 
  
Nevertheless, it will be mandatory to enter into a hedging insurance by any other 
participating centre of this clinical trial, in the case that it is mandatory according to the 
laws of their country. 
 
No funding is provided for the study. 
 
 
15. Publication policy 
 
The Sponsor takes the commitment of publishing the results of the study; despite they 
are good or bad. 
 
Promoter and participating Centre agree that publications or presentations of any of 
the results from the study shall be in accordance with accepted scientific practice, 
academic standards and customs.   
 

 
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Authorship and other related publications questions shall be addressed in accordance 
with the principles of the ‘Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals’ and in accordance with the requirements of the respective 
medical journal. 
 
Sponsor agrees to ensure co-authorship for clinical co-investigators on any proposed 
multicentre publication.  
 
Sponsor and participating Centres agree that at first they will strive to make a joint 
publication. After such joint publication or one year after termination of the study the 
following shall be agreed: 
 
As a general principle, the parties agree that prior to submission of a publication or any 
other dissemination of the results, including oral presentation, the Sponsor shall have 
the right to prior review and comment on the content of the material to be published or 
presented within sixty (60) days following the receipt of the publication or any other 
dissemination of the results, and Participating Centre ensures that it will take 
Promoter’s comments into due consideration.  
 
 
16. Legal Issues 
 
Both the Promoter and the participating Centre will enter into a contract before they 
can start randomizing patients. 
This contract will prevail in case of lack of agreement from any of the parts. 
 
 
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27. Steenis LJP, Verhoeven M, Hessen DJ, van Baar AL. Parental and professional 
assessment of early child development: The ASQ-3 and the Bayley-III-NL. Early Human 
Development. 2015; 91:217–225  
 
28. Van ’t Hooft J, Cuijpers C, van der Lee JH, Liem S, Schuit E, Steenis L, van 
Wassenaer-Leemhuis AG, van Baar AL, Bekedam D, Mol BWJ, van der Beek C. Long-
term effects of cervical pessary for preterm birth prevention in twin pregnancy with short 
cervix: a 3 years follow-up of the ProTwin trial. AJOG2016. 
 
18. Annex 
 

 
THE PROMETHEUS-TRIAL 
 Version 1.3 
  
Confidential 
25
Annex I. Technical details of the device.  
 
The Arabin cervical pessary 
CE-certified for preventing spontaneous preterm birth (CE 0482 / EN ISO 13485: 2012 
+ AC:2012 annex III of the council directive 93/42 EEC). 
 
This pessary is used to treat pregnant women with cervical incompetence in order to 
support the cervix and sacralise it towards the sacrum.  
It may be indicated in pregnancies with a history of premature labour, multiple 
pregnancies or mothers who are exposed to physical strain (e.g. standing for a long 
time). It may also be indicated in pregnant women suffering from prolapse of the 
genital organs. 
The cerclage pessary can easily be folded and inserted without pain.  
 
In general, cerclage pessaries should have a height of 21-25 mm in singleton 
pregnancies and a height of 25-30 mm in multiple pregnancies or pregnant patients 
with complaints of prolapse. The width of the upper and lower diameter should be 
chosen depending on the individual constitution of the pregnant patient. 
Cerclage pessaries can be ordered in a non-perforated or perforated version. The 
perforations facilitate discharge to pass. 
 
Sizes and Models: Cerclage pessaries are classified according to 
• 
The lower larger diameter (65 or 70 mm)  
• 
The height (17, 21, 25, 30 mm) 
• 
The upper smaller diameter (32 or 35 mm) 
 
Dr. Arabin online shop. http://www.dr-arabin.de/e/cerclage.html