This study compares the effectiveness of cervical pessary to vaginal progesterone for prevention of preterm birth in women with singleton pregnancies and a cervix ≤25 mm. Participants will be randomly assigned in a 1:1 ratio to receive cervical pessary or vaginal progesterone.
This open label, multi-center, randomized controlled trial aims to compare the effectiveness of cervical pessary to vaginal progesterone for prevention of PTB in women with singleton pregnancies and a cervix ≤25 mm. All women at 16 0/7 to 22 0/7 weeks with singleton pregnancies will undergo cervical length (CL) measurement and digital examination at screening routinely. Women with a CL ≤25 mm will be eligible for the study. Subjects meeting the study criteria will be randomized into two groups: (1) treated with cervical pessary (Arabin) or (2) treated with 200 mg vaginal progesterone, once daily. After written informed consent, women will be randomly assigned in a 1:1 ratio to receive a cervical pessary or progesterone. Assignment to treatment allocation will be done via a web portal hosted by HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE Research Center, with a permuted random block size of 2, 4 or 6. Blinding will not be possible due to the nature of interventions. For those who randomised to pessary group, a pessary certified by European Conformity (Arabin®, Dr Arabin GmbH \& Co KG, Germany) will be inserted through the vagina, upward around the cervix by 2-4 senior clinicians, who had experienced with pessary used at each site, within one week of randomization. Women allocated to progesterone group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200 mg, Actavis, United Kingdom), once daily at bedtime. They will be given a monitoring sheet and instructed to note everyday the date of using. In case of premature rupture of membranes, active vaginal bleeding, other signs of preterm labor or severe patient discomfort, the pessary may be removed. If participants develop (threatened) preterm labor, they will receive treatment per local protocol. Intervention will be stopped at 370/7 weeks of gestation or at delivery. Along side with this trial, another study will be conducted to determine how changes in peripheral blood and cervical inflammatory markers are impacted by progesterone versus pessary. Because of that, participants will be asked to take 5 ml blood sample and cervical-vaginal discharge sampling at the time of randomization, 4-8 weeks after randomization and before giving birth. A cost-effectiveness analysis will also be conducted alongside this RCT. Data will be reported in a separated paper.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
804
Arabin (cervical pessary) will be inserted at 16-22 weeks and removed at 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort
Vaginal progesterone (Cyclogest 200 mg) once a day will be used, from 16-22 to 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort.
My Duc Phu Nhuan Hospital
Ho Chi Minh City, Phu Nhuan, Vietnam
RECRUITINGMỹ Đức Hospital
Ho Chi Minh City, Tan Binh, Vietnam
RECRUITINGQuang Ninh Obstetrics and Pediatrics Hospital
Quang Ninh, Vietnam
RECRUITINGRate of preterm birth <37 weeks of gestation by any cause
Birth before 37 weeks
Time frame: From date of randomisation until 36 6/7 weeks
Gestational age at delivery
Gestational age at delivery
Time frame: At birth
Time from randomization to delivery
Time interval between randomisation and delivery
Time frame: From date of randomisation until the date of delivery.
Rate of preterm birth before 28 weeks of gestation
Birth before 28 weeks
Time frame: From date of randomisation until 27 6/7 weeks
Rate of preterm birth before 34 weeks of gestation
Birth before 34 weeks
Time frame: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <28 weeks
Birth spontaneously before 28 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Time frame: From date of randomisation until 27 6/7 weeks
Rate of spontaneous preterm birth <34 weeks
Birth spontaneously before 34 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Time frame: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <37 weeks
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Birth spontaneously before 37 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Time frame: From date of randomisation until 36 6/7 weeks
Rate of iatrogenic preterm birth <28 weeks
Birth non-spontaneously before 28 weeks' gestation
Time frame: From date of randomisation until 27 6/7 weeks
Rate of iatrogenic preterm birth <34 weeks
Birth non-spontaneously before 34 weeks' gestation
Time frame: From date of randomisation until 33 6/7 weeks
Rate of iatrogenic preterm birth <37 weeks
Birth non-spontaneously before 37 weeks' gestation
Time frame: From date of randomisation until 36 6/7 weeks
Rate of onset of labor
Spontaneous, labor induction, elective C-section
Time frame: At birth
Rate of modes of delivery
Vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor)
Time frame: At birth
Rate of all live births at any gestational age
The birth of at least one newborn, regardless of gestational age, that exhibits any sign of life such as respiration, heartbeat, umbilical pulsation or movement of voluntary muscles
Time frame: At birth
Rate of use of tocolytic drugs
Use of any tocolytic drug to treat preterm labour
Time frame: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of antenatal corticosteroids
Use of antenatal corticosteroids to prevent respiratory distressed syndrome
Time frame: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of MgSO4 for neuroprotection
Use of MgSO4 for neuroprotection
Time frame: From 28 0/7 to 31 6/7 weeks' gestation
Rate of preterm premature rupture of membranes
Prelabour rupture of membranes and gestational age less than 37 weeks
Time frame: From randomization to less than 37 weeks, up to 21 weeks
Length of maternal admission for preterm labor (days)
Number of admission days for treatment of preterm labour
Time frame: From randomization to 37 week
Rate of chorioamnionitis
Intraamniotic infection
Time frame: From randomization to delivery, up to 28 weeks
Rate of maternal mortality
Death of the mother
Time frame: From randomization to delivery, up to 28 weeks
Birthweight (mean)
Weight of baby born
Time frame: At birth
Birthweight <1500 g
Weight of baby born \<1500g
Time frame: At birth
Birthweight <2500 g
Weight of baby born \<2500g
Time frame: At birth
Rate of congenital anomalies
Any congenital anomalies detected in baby born
Time frame: At birth
5-min Apgar score
Apgar score at 5 minute after birth. 5-minute Apgar score of 7-10 as reassuring, a score of 4-6 as moderately abnormal, and a score of 0-3 as low in the term infant and late-preterm infant.
Time frame: At birth
5-min Apgar score <7
Apgar score at 5 minute after birth \<7. An increased relative risk of cerebral palsy.
Time frame: At birth
Rate of admission to neonatal intensive care unit (NICU)
Admission to neonatal intensive care unit of baby
Time frame: Up to 28 days of life after the due day
Length of NICU admission
Number of admission days to NICU
Time frame: Up to 28 days of life after the due day
Rate of death before discharge
Death of newborn before discharge from nursery
Time frame: Up to 28 days of life after the due day
Rate of neonatal death
Death of a live-born infant within the first 28 days of life after the due day
Time frame: Up to 28 days of life after the due day
Rate of perinatal death
Intrauterine fetal death after 20 weeks of gestation, or neonatal death
Time frame: After 20 weeks of gestation to 28 days of life after the due day
Rate of stillbirth
Baby born with no signs of life at or after 20 weeks' gestation
Time frame: After 20 weeks of gestation until the date of delivery
Rate of composite of poor perinatal outcomes
Foetal or neonatal death, intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis
Time frame: Up to 28 days of life after the due day
Rate of respiratory distress syndrome
presence of tachypnoea \>60/minute, sternal recession and expiratory grunting, need for supplemental oxygen, and a radiological picture of diffuse reticulogranular shadowing with an air bronchogram
Time frame: Up to 28 days of life after the due day
Rate of periventricular haemorrhage II B or worse
Repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al
Time frame: Up to 28 days of life after the due day
Rate of necrotizing enterocolitis
Diagnosed according to Bell
Time frame: Up to 28 days of life after the due day
Rate of proven sepsis
The combination of clinical signs and positive blood cultures
Time frame: Up to 28 days of life after the due day
Rate of maternal vaginal side effects
Including vaginal discharge, vaginal bleeding, vaginal infection (confirmed by vaginal discharge culture)
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Vaginal pain Score
Evaluated by VAS numerical rating scale. Assessments with units on a Scale.
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Rate of pessary repositioning
After pessary initial placement, requiring to reposition the pessary by any reasons
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Rate of maternal cervical side effects
Including necrosis or rupture of the cervix, cervical laceration
Time frame: From date of randomisation until delivery, which is up to 24 weeks