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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03418012




Registration number
NCT03418012
Ethics application status
Date submitted
23/01/2018
Date registered
31/01/2018
Date last updated
5/05/2020

Titles & IDs
Public title
Prevention of sPTB With Early Cervical Pessary Treatment in Women at High Risk for PTB
Scientific title
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
Secondary ID [1] 0 0
BHFKIK2018P
Universal Trial Number (UTN)
Trial acronym
Prometheus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm Birth 0 0
Premature Birth 0 0
Condition category
Condition code
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Reproductive Health and Childbirth 0 0 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - cervical pessary
Other interventions - Control-Group

Experimental: Cervical Pessary-Group - Cervical Pessary Group: placement of the cervical pessary (non-invasive) at enrolment including a transvaginal ultrasound to verify its correct fit. Removal of the cervical pessary (non-invasive) in a regular preventive examination at WoG 37

Other: Control-Group - Control-Group women receive management as usual; i.e. expectant management with interventions only in terms of a tertiary prevention of PTB according to guidelines for premature rupture of membranes, premature labour or other pregnancy complications


Treatment: Devices: cervical pessary
Intervention: Device: Cervical pessary: After Having excluded a vaginal infection insertion of the cervical pessary (silicone ring) directly after enrollment. After insertion verification of correct fit of the cervical pessary by transvaginal ultrasound. Removal of the pessary at 37+0 weeks of gestation, or before if any unexpected event occurs. Except for the insertion of the pessary the obstetrical management during the remainder of the pregnancy will be usual management.

Other interventions: Control-Group
Intervention: Other: expectant management: expectant management is usual care; interventions only in terms of a tertiary prevention of PTB according to guidelines for premature rupture of membranes, premature labour or other pregnancy complications

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Children`s survival without neurodevelopmental disability at the age of 3 years - mortality rate will be recorded
neurodevelopmental disability will be assessed by the Ages & Stages questionnaire and by medical examination at 3 years of age (corrected age for prematurity)
Timepoint [1] 0 0
assessment of the newborn at age of 3 years (corrected age for prematurity)
Secondary outcome [1] 0 0
rate of preterm birth - rate of delivery before weeks of gestation: 36+6 / 33+6 / 31+6 / 29+6 / 27+6
Timepoint [1] 0 0
randomisation till birth, maximum 25 weeks
Secondary outcome [2] 0 0
time till birth - time span from enrollment till birth
Timepoint [2] 0 0
days from randomisation till birth, maximum 30 weeks
Secondary outcome [3] 0 0
birth weight of the neonate - birth weight of the neonate in grams recorded at hospital
Timepoint [3] 0 0
at birth
Secondary outcome [4] 0 0
Fetal or neonatal death - death of the neonate before birth /within first 24 hours
Timepoint [4] 0 0
at birth, first 24 hours after birth
Secondary outcome [5] 0 0
Need (days) for neonatal special care unit - Number of days the neonate is transferred to ICU for medical interventions other than supervision
Timepoint [5] 0 0
birth till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [6] 0 0
neonatal morbidity - rate of major adverse neonatal outcomes: Intraventricular Haemorrhage III-IV, Retinopathy of prematurity, Respiratory Distress Syndrome II-IV, Need for ventilation > 72 h, Necrotising enterocolitis, Proven or suspected sepsis (antibiotics >5 days)
Timepoint [6] 0 0
birth till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [7] 0 0
harm from intervention - recording any harm of the neonate deriving from the cervical pessary
Timepoint [7] 0 0
birth till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [8] 0 0
maternal death - rate of maternal death due to pregnancy/birth
Timepoint [8] 0 0
enrollment till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [9] 0 0
rate of significant maternal adverse events - rate of : heavy bleeding, cervical tear due to pessary placement, uterine rupture
Timepoint [9] 0 0
enrollment till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [10] 0 0
infection/inflammation - rate of maternal infection and/or inflammation during pregnancy / birth
Timepoint [10] 0 0
enrollment till discharge from hospital, recorded for at least first 48 hrs after birth
Secondary outcome [11] 0 0
physical or psychological intolerance to pessary - rate of maternal physical or psychological intolerance to pessary during pregnancy
Timepoint [11] 0 0
time from placement of cervical pessary at enrollment till removal of cervical pessary at WoG 37, maximum 25 weeks
Secondary outcome [12] 0 0
Hospitalisation for threatened preterm labour before 31+6 weeks - Hospitalisation for threatened preterm labour before 31+6 weeks: recording of days of hospitalisation and tocolytic treatment: type / days / dose
Timepoint [12] 0 0
randomization till birth, maximum 20 weeks
Secondary outcome [13] 0 0
premature rupture of membranes (PRoM) before 31+6 weeks - rate of women with premature rupture of membranes (PRoM) before 31+6 weeks
Timepoint [13] 0 0
randomization till birth, maximum 20 weeks

Eligibility
Key inclusion criteria
- Women with a singleton pregnancy and a history of at least one previous preterm
delivery before 34+0 weeks and/or a history of at least one previous cervical surgery

- 12+0 - 16+0 weeks of gestation at time of randomization

- only women with minimum age of 18 and capable of giving consent
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- major fetal abnormalities

- uterine malformation, placenta previa totalis

- Cerclage prior to randomization

- At randomisation: active vaginal bleeding and/or spontaneous rupture of membranes
and/or painful regular uterine contractions

- silicone allergy

- current participation in other RCT

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
University of Adelaide - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
Germany
State/province [2] 0 0
Frankfurt
Country [3] 0 0
Germany
State/province [3] 0 0
Hamburg
Country [4] 0 0
Germany
State/province [4] 0 0
Homburg
Country [5] 0 0
Greece
State/province [5] 0 0
Athen
Country [6] 0 0
Greece
State/province [6] 0 0
Thessaloníki
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Other
Name
Bürgerhospital Frankfurt
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Prevention of preterm birth (PTB) is a key factor for a positive short-term and long-term
outcome of the newborn children as mortality and morbidity are inversely related to
gestational age at delivery. Consequently every week of prolonged pregnancy will have a
tremendous effect concerning the outcome of the new-borns, subsequently for their parents and
society as well.

The proposed RCT aims to evaluate the impact of a preventive pessary treatment on the
prevention of preterm birth in women with a singleton pregnancy who are at high risk of
spontaneous preterm birth (sPTB) due to a history of at least one previous preterm delivery
and/or a history of previous cervical surgery. In accordance with the results by "van´t Hooft
et al. 2016" an approximately 20% higher percentage of children's long-term survival without
neurodevelopmental disability is expected for the pessary group in comparison with usual
management (=control group) on basis of a reduction of prematurity < 34 week of gestation
(WoG).

The primary outcome measure for the effect of the pessary treatment in comparison to
expectant management will be the children's long-term survival (3yrs) without
neurodevelopmental disability. Secondary endpoints assess the impact of a preventive pessary
placement on the prevention of preterm birth and its resulting risk on mortality and
morbidity for the neonates.
Trial website
https://clinicaltrials.gov/show/NCT03418012
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ioannis Kyvernitakis, MD, PhD
Address 0 0
Asklepios Clinic Barmbek
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ioannis Kyvernitakis, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
+49 1768248
Fax 0 0
Email 0 0
janniskyvernitakis@gmail.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03418012