Preterm Birth, Short Cervix
Conditions
Keywords
Preterm Birth, Singleton Pregnancies, Short Cervix, Pessary, Progesterone
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.
Interventions
DEVICECervical pessary
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
DRUGVaginal 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.
Sponsors
My Duc Phu Nhuan Hospital HCMC, Vietnam
Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam
Mỹ Đức Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Participants will be randomised to either pessary or progesterone in a 1:1 ratio with a variable block size of 2, 4 or 6.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 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 |
| Gestational age at delivery | At birth | Gestational age at delivery |
| 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 |
| Rate of proven sepsis | Up to 28 days of life after the due day | The combination of clinical signs and positive blood cultures |
Countries
Vietnam
Contacts
Primary ContactVinh Q Dang, MD
Backup ContactMinh N Chau, MD
Outcome results
None listed