An interventional study of Cervical cerclage and Vaginal progesterone in Preterm Birth and Short Cervix, sponsored by Mỹ Đức Hospital. Recruiting at 1 site in Vietnam. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-16.
Sponsored by Mỹ Đức Hospital · Not applicable, Interventional, and Prevention
This study compares the effectiveness of cervical cerclage with vaginal progesterone to vaginal progesterone only for the prevention of preterm birth in women with a singleton pregnancy and a short cervical length. Participants will be randomly assigned in a 1:1 ratio to receive cerclage plus progesterone or progesterone only.
This open-label, multi-center, randomized controlled trial aims to compare the effectiveness of cervical cerclage with vaginal progesterone (the combined therapy group) to vaginal progesterone only (the progesterone-only group) for the prevention of preterm birth in women with a singleton pregnancy and a cervical length ≤ 25mm.
After written informed consent, women will be randomly assigned in a 1:1 ratio to receive a cervical cerclage with vaginal progesterone or vaginal progesterone only. Randomization will be carried out by entering participant details into HOPE Epi® (a web portal of HOPE Research Center, My Duc Hospital). Treatment allocation will be assigned according to a computer-generated randomization list stored in the online system, with a permuted random block size of 2, 4, or 6. Blinding will not be possible due to the nature of interventions. However, neonatologists assessing the neonates will be unaware of treatment allocation. Apart from randomization, participants will be monitored and treated according to local protocol.
All women at 16 0/7 to 24 0/7 weeks' gestation with a singleton pregnancy will undergo cervical length measurement and digital examination at screening routinely. Women with a cervical length ≤25 mm will be eligible for the study. Eligible women will further undergo a speculum examination to assess the feasibility of treatment with either cervical cerclage or vaginal progesterone and to exclude premature rupture of the membranes, acute vaginitis, and cervicitis. Only women in whom the clinician assesses both treatments as feasible will be randomized.
Women allocated to a combined therapy group will receive the intervention according to local protocol within a week after randomization. Briefly, cervical cerclage (McDonald technique) will be performed in the operation theatre. From the same day of undergoing cerclage, participants will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a participant diary sheet.
Women allocated to the progesterone-only group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a participant diary sheet.
In both groups, interventions will be stopped at 37 0/7 weeks of gestation or at delivery.
Primary analysis will be performed on an intention-to-treat basis. The primary outcome, the time from randomization to delivery, will be summarised as median and IQR and compared between the two arms using the Mann-Whitney test. A mean ratio with a 95% confidence interval will be calculated to assess the effect of the treatment. Kaplan-Meier and Cox proportional hazard analysis will be performed in which the gestational week at delivery will be the time scale, continued pregnancy will be the event, and results will be compared with a log-rank test. Hazard ratio (HR) values will be estimated using a Cox proportional hazards model, with a formal test of the proportional hazard assumption.
The secondary outcome will be analysed by reporting continuous variables as mean and standard deviation for normally distributed variables or median and interquartile range (Q1; Q3) for non-normally distributed variables. Categorical variables will be presented as the number of events and proportions. Student T-test or Mann-Whitney U test will be used for continuous outcomes to compare the differences between groups. For categorical outcomes, the Chi-squared or Fisher exact test will be used. In the case of dichotomous endpoints, the relative risk (RR) and 95% confidence interval (CI) values will be calculated using the Wald or Adjusted Wald methods for a small proportion. Per-protocol analysis will also be conducted if needed.
A prespecified subgroup analysis will be performed by quartiles of cervical length, which tested for interaction between cervical length and the treatment effect on the primary outcome, the major secondary outcome and PTB \<28, \<34, \<37 weeks.
The p-values \<0.05 will be considered to indicate statistical significance. Statistical analyses will be performed using the R statistical software.
Details of the analysis will be described in a separate statistical analysis plan developed during the study and finalized before the data lock. Cost data will be collected and will be reported on a separated paper.
Interim analysis will be done after completion of data recruitment of the first 162 participants, by an independent Data Safety Monitoring Committee. The Data Safety Monitoring Committee will be asked to assess the primary endpoint for effectiveness. Also, the Data Safety Monitoring Committee will be provided insight into the serious adverse events (SAEs) that have occurred. The interim analysis will be conducted using a two-sided significant test with the Haybittle-Peto spending function and a type I error rate of 5 percent with p \<0.001 (Z alpha = 3.29) being a reason to stop the trial. The continuation of the study will depend on the advice of Data Safety Monitoring Committee.
2,554 studies on the registry are indexed under Premature Birth; 498 are open to participants now.
This study's planned enrollment of 328 is above the median of 84 across 1,688 interventional studies indexed under Premature Birth.
Browse Premature Birth studies →Mỹ Đức Hospital is the lead sponsor of 55 studies on the registry; 20 are open to participants now.
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Exclusion Criteria:
(*Women with acute cervicitis, vaginitis or severe vaginal discharge are eligible once they have been treated and if they have a CL ≤25 mm between 16 0/7 - 24 0/7 weeks of gestation.)
Women will be receiving the cervical cerclage according to local protocol within a week after randomization, using the McDonald technique. Within one day after the procedure, they will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a patient diary sheet.
Procedure: Cervical cerclage · Drug: Vaginal progesterone
Women allocated to the progesterone only group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200mg, Actavis, United Kingdom), once daily at bedtime. Participants will be asked to record their drug application in a patient diary sheet.
Drug: Vaginal progesterone
Cervical cerclage using the McDonald technique under anaesthesia.
Cyclogest® 200mg, Actavis, United Kingdom, applied once daily at bedtime.
Also known as: Cyclogest® 200 mg
Time from randomization to delivery
Number of days between randomization and delivery
Time frame: From date of randomization until the date of delivery
Composite poor neonatal outcomes (major sencondary endpoint)
Stillbirth or neonatal death, intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.
Time frame: From 20 weeks of gestation to 28 days after estimated due date
Miscarriage <22 weeks (late miscarriage)
spontaneous loss of pregnancy between 12 to 22 weeks is termed as late miscarriage
Time frame: From date of randomization to 22 weeks of gestation
Gestational age at delivery
Gestational age at delivery
Time frame: At delivery
Preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation
Preterm birth is defined as any birth ≥ 22 and \< 37 completed weeks of gestation. Any birth \< 22 weeks is defined as late miscarriage
Time frame: At delivery
Spontaneous preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation
Spontaneous preterm birth, including preterm labour, preterm spontaneous rupture of membranes, preterm premature rupture of membranes, and cervical weakness before 24 weeks, 28 weeks, 32 weeks, 34 weeks, and 37 weeks of gestation, respectively, does not include indicated preterm delivery for maternal or fetal conditions.
Time frame: At delivery
Iatrogenic preterm birth <24 weeks, <28 weeks, <32 weeks, <34 weeks and <37 weeks of gestation
Iatrogenic preterm birth, including planned delivery that occurs before 24 weeks, 28 weeks, 32 weeks, 34 weeks, and 37 weeks of gestation, respectively, due to maternal and/or fetal causes.
Time frame: At delivery
Onset of labor
Classified as spontaneous, labor induction, or elective C-section.
Time frame: At birth
Mode of delivery
Classified as vaginal delivery or C-section (elective, suspected fetal distress, non-progressive labor).
Time frame: At birth
Live birth
Defined as the complete expulsion or extraction from a woman of a product of fertilization after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown
Time frame: At birth
Use of tocolytic drugs
Use of any tocolytic drug to treat preterm labour
Time frame: From 24 0/7 to 33 6/7 weeks' gestation
Use of Post cerclage antibiotics
Use of any treatment antibiotics after the cerclage procedure
Time frame: Within one week after the cerclage procedure
Use of antenatal corticosteroids
Use of antenatal corticosteroids to prevent respiratory distressed syndrome
Time frame: From 24 0/7 to 33 6/7 weeks' gestation
Use of MgSO4 for neuroprotection
Use of MgSO4 for neuroprotection
Time frame: From 24 0/7 to 31 6/7 weeks' gestation
Fetal growth restriction
It is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction.
Time frame: From randomization to delivery
Preterm premature rupture of membranes
When membrane rupture occurs before labor and before 37 weeks of gestation
Time frame: From randomization to before 37 weeks of gestation
Length of maternal admission for labour
Number of maternal admission days for labour
Time frame: Up to 2 weeks after birth
Total length of admission for threatened preterm labor
Number of admission days for treatment of preterm labour
Time frame: From 22 0/7 to 36 6/7 weeks of gestation
Chorioamnionitis
Intraamniotic infection (diagnosed according to The American College of Obstetricians and Gynecologists Committee on Obstetric Practice No 712, 2017 (reaffirmed 2022))
Time frame: From randomization to delivery
Maternal mortality
female deaths from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy
Time frame: From randomization to during pregnancy and childbirth or within 42 days of termination of pregnancy
Maternal side effects
Vaginal discharge, vaginal bleeding, vaginal infection (confirmed by vaginal discharge culture), preterm premature rupture of membranes, chorioamnionitis, necrosis or rupture of the cervix, cervical laceration, vaginal or bladder injury.
Time frame: From date of randomization until delivery
Birthweight
Weight of the newborn measured right after delivery
Time frame: At birth
Birthweight <1500 g
Weight of the newborn \<1500g
Time frame: At birth
Birthweight <2500 g
Weight of the newborn \<2500g
Time frame: At birth
Congenital anomalies
Structural or functional disorders that occur during intra-uterine life and can be identified prenatally and at birth. Congenital anomalies can be caused by single gene defects, chromosomal disorders, multifactorial inheritance, environmental teratogens, and micronutrient deficiencies. The time of identification will be reported.
Time frame: After randomization to at birth
1-min Apgar score
Apgar score at 1 minute after birth
Time frame: 1 min after birth
5-min Apgar score
Apgar score at 5 minute after birth
Time frame: 5 min after birth
Admission to neonatal intensive care unit
Admission to neonatal intensive care unit of baby
Time frame: At birth and up to 28 days after birth
Length of stay in the neonatal intensive care unit
Number of admission days to neonatal intensive care unit
Time frame: Up to 28 days after estimated due date
Neonatal death
Death of a live-born baby within 28 days of birth
Time frame: Within the first 28 days of life after delivery
All stillbirth
Defined as the death of a fetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age. The death is determined by the fact that, after such separation, the fetus does not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles. It includes deaths occurring during labor. All stillbirth will be defined as a baby born with no signs of life at ≥ 20 weeks of gestation
Time frame: After 20 weeks of gestation
Early stillbirth
A baby born with no signs of life at ≥ 20 weeks and \< 28 weeks of gestation
Time frame: ≥ 20 weeks and < 28 weeks of gestation
Late stillbirth
A baby born with no signs of life at ≥ 28 weeks of gestation
Time frame: After 28 weeks of gestation
Perinatal death
Either stillbirth or neonatal death
Time frame: From 20 weeks of gestation to the first 28 days of life after delivery
Respiratory distress syndrome
Diagnosed as the 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 after estimated due date
Intraventricular haemorrhage II B or worse
Diagnosed by 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 after estimated due date
Necrotizing enterocolitis
An acquired gastrointestinal disease associated with significant morbidity and mortality in prematurely born neonates. Necrotizing enterocolitis will be diagnosed according to Bell et al., 1978
Time frame: Up to 28 days after estimated due date
Neonatal sepsis
Diagnosed on the combination of clinical signs and positive blood cultures of the newborn
Time frame: Up to 28 days after estimated due date
Plan to share: No
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