Pessary Versus Progesterone in Singletons
- Conditions
- Preterm BirthShort Cervix
- Interventions
- Device: Cervical pessary
- Registration Number
- NCT04300322
- Lead Sponsor
- Mỹ Đức Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 804
- Singleton pregnancies
- Cervical length ≤ 25 mm, measured by TVS at the second-trimester ultrasonography (16 0/7-22 0/7 weeks of gestation)
- Not participating in any other study which has intervention on maternity or fetus at the same time
- Provision of written informed consent to participate as shown by a signature on the patient consent form.
- Cervical dilation with visible amniotic membranes or amniotic membranes prolapsed into the vagina
- Major congenital abnormalities of the fetus
- Presence of severe vaginal discharge
- Presence of vaginitis or cervicitis
- Presence of vaginal bleeding
- Preterm premature rupture of membranes
- Premature labor without ruptured membrane at the time of screening
- Suspected chorioamnionitis
- Unable to have cervical pessary inserted
- Cerclage or pessary in place
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cervical pessary Cervical pessary Cervical pessary (Arabin) will be inserted to participants 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 Vaginal Progesterone 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.
- Primary Outcome Measures
Name Time Method Rate of preterm birth <37 weeks of gestation by any cause From date of randomisation until 36 6/7 weeks Birth before 37 weeks
- Secondary Outcome Measures
Name Time Method Gestational age at delivery At birth Gestational age at delivery
Time from randomization to delivery From date of randomisation until the date of delivery. Time interval between randomisation and delivery
Rate of preterm birth before 28 weeks of gestation From date of randomisation until 27 6/7 weeks Birth before 28 weeks
Rate of preterm birth before 34 weeks of gestation From date of randomisation until 33 6/7 weeks Birth before 34 weeks
Rate of spontaneous preterm birth <28 weeks From date of randomisation until 27 6/7 weeks Birth spontaneously before 28 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Rate of spontaneous preterm birth <34 weeks From date of randomisation until 33 6/7 weeks Birth spontaneously before 34 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Rate of spontaneous preterm birth <37 weeks From date of randomisation until 36 6/7 weeks Birth spontaneously before 37 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Rate of iatrogenic preterm birth <28 weeks From date of randomisation until 27 6/7 weeks Birth non-spontaneously before 28 weeks' gestation
Rate of iatrogenic preterm birth <34 weeks From date of randomisation until 33 6/7 weeks Birth non-spontaneously before 34 weeks' gestation
Rate of iatrogenic preterm birth <37 weeks From date of randomisation until 36 6/7 weeks Birth non-spontaneously before 37 weeks' gestation
Rate of onset of labor At birth Spontaneous, labor induction, elective C-section
Rate of modes of delivery At birth Vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor)
Rate of all live births at any gestational age At birth 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
Rate of use of tocolytic drugs From 24 0/7 to 36 6/7 weeks' gestation Use of any tocolytic drug to treat preterm labour
Rate of use of antenatal corticosteroids From 24 0/7 to 36 6/7 weeks' gestation Use of antenatal corticosteroids to prevent respiratory distressed syndrome
Rate of use of MgSO4 for neuroprotection From 28 0/7 to 31 6/7 weeks' gestation Use of MgSO4 for neuroprotection
Rate of preterm premature rupture of membranes From randomization to less than 37 weeks, up to 21 weeks Prelabour rupture of membranes and gestational age less than 37 weeks
Length of maternal admission for preterm labor (days) From randomization to 37 week Number of admission days for treatment of preterm labour
Birthweight (mean) At birth Weight of baby born
Birthweight <1500 g At birth Weight of baby born \<1500g
Birthweight <2500 g At birth Weight of baby born \<2500g
Rate of congenital anomalies At birth Any congenital anomalies detected in baby born
5-min Apgar score At birth 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.
5-min Apgar score <7 At birth Apgar score at 5 minute after birth \<7. An increased relative risk of cerebral palsy.
Rate of admission to neonatal intensive care unit (NICU) Up to 28 days of life after the due day Admission to neonatal intensive care unit of baby
Length of NICU admission Up to 28 days of life after the due day Number of admission days to NICU
Rate of death before discharge Up to 28 days of life after the due day Death of newborn before discharge from nursery
Rate of neonatal death Up to 28 days of life after the due day Death of a live-born infant within the first 28 days of life after the due day
Rate of perinatal death After 20 weeks of gestation to 28 days of life after the due day Intrauterine fetal death after 20 weeks of gestation, or neonatal death
Rate of chorioamnionitis From randomization to delivery, up to 28 weeks Intraamniotic infection
Rate of maternal mortality From randomization to delivery, up to 28 weeks Death of the mother
Rate of stillbirth After 20 weeks of gestation until the date of delivery Baby born with no signs of life at or after 20 weeks' gestation
Rate of composite of poor perinatal outcomes Up to 28 days of life after the due day Foetal or neonatal death, intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis
Rate of respiratory distress syndrome Up to 28 days of life after the due day 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
Rate of periventricular haemorrhage II B or worse Up to 28 days of life after the due day Repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al
Rate of necrotizing enterocolitis Up to 28 days of life after the due day Diagnosed according to Bell
Rate of proven sepsis Up to 28 days of life after the due day The combination of clinical signs and positive blood cultures
Rate of maternal vaginal side effects From date of randomisation until delivery, which is up to 24 weeks Including vaginal discharge, vaginal bleeding, vaginal infection (confirmed by vaginal discharge culture)
Vaginal pain Score From date of randomisation until delivery, which is up to 24 weeks Evaluated by VAS numerical rating scale. Assessments with units on a Scale.
Rate of pessary repositioning From date of randomisation until delivery, which is up to 24 weeks After pessary initial placement, requiring to reposition the pessary by any reasons
Rate of maternal cervical side effects From date of randomisation until delivery, which is up to 24 weeks Including necrosis or rupture of the cervix, cervical laceration
Trial Locations
- Locations (3)
Quang Ninh Obstetrics and Pediatrics Hospital
🇻🇳Quang Ninh, Vietnam
My Duc Phu Nhuan Hospital
🇻🇳Ho Chi Minh City, Phu Nhuan, Vietnam
Mỹ Đức Hospital
🇻🇳Ho Chi Minh City, Tan Binh, Vietnam