Clinical trial NCT02623881: Cervical Pessary vs. Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies
Official title: The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies: a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Keywords: Cervical pessary
Vaginal progesterone
Twins
Premature birth
Lead sponsor: Vietnam National University
Sponsor class: OTHER
Collaborators: name: Mỹ Đức Hospital
First posted: 2015-12-08
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the effectiveness of cervical pessary (Arabin) and vaginal progesterone for preventing premature birth in twin pregnancies after IVF

Detailed description: This will be a randomized controlled trial.

Women with twin pregnancies, at 16-22 weeks of gestation, will be invited to participate into the study.

Subjects meeting the study criteria will be randomized into two groups: (1) treated with cervical pessary (Arabin) or (2) treated with 400mg vaginal progesterone, once daily. Randomization will be done by third party via telephone, using a computer generated random list, with a variable block size of 2, 4 or 8. Apart from randomization, patients will be examined and treated according to local protocol.

Patients in pessary group will have an Arabin pessary placed within a week after randomization. A pessary certified by European Conformity (CE0482, MED/CERT ISO 9003/ EN 46003; Dr. Arabin, Witten, Germany) will be inserted through the vagina of the woman in the recumbent position and will be placed upward around the cervix. The research-team members who inserted the Arabin pessary have experience with Arabin pessary for singleton pregnancy before.

Patients in progesterone group will use vaginal progesterone (Cyclogest 400mg) once daily before bedtime, starting from the day of randomization onwards. They will be given a monitoring sheet and instructed to note everyday the date of using. If they forget one dose of any night, and remember it in the next morning or afternoon, they will use immediately the forgotten dose and continue with the dose of that day at night. If one dose is missed until the next evening, there will be no compensation use, they will only use the dose of the next day. Any change in using medication should be noted in the monitoring sheet.

In both groups, intervention will be stopped at 36 weeks of gestation or at delivery. All the participants will have follow-up visits every 4 weeks. If patients develop (threatened) preterm labor, they will receive treatment as routine practice.

Statistical analyses will be by intention to treat. For dichotomous endpoints, we will calculate rates. These will be compared by calculating a relative risk and a 95% confidence interval. Between-group differences in non-continuous variables will be assessed using the χ2-test. Results of continuous variables were given in mean ± SD or in percentage. Between-group differences of continuous variables were assessed with the Student's t-test. We will consider correlation between neonatal endpoints when we analyse at the level of the child. We assessed time to delivery by Cox proportional hazard analysis and Kaplan-Meier estimates, and compared results with a log-rank test. We plan an exploratory subgroup analysis in women with a cervical length of less than the 25th percentile (according to the distribution in all twins), as well as 25th - 50th percentile, 50th - 75th percentile and \> 75th percentile. We also plan an exploratory subgroups analyses for chorionicity. A p-value \< 0.05 will be considered to indicate a statistically significant difference. The analysis will be done with statistical Package for Social Sciences version 19 (SPSS, USA).

Sample size has been set at 290. This was incorporated in an amendment of the protocol, and was approved by the IRB on 22 Sept 2016.

Eligibility criteria: Inclusion Criteria:

To be eligible for enrolment into this trial, each female subject must fulfil all of the following criteria at the start of enrolment, unless specified otherwise:

* Women with a twin pregnancy (mono- and di-chorionic)
* 16 0/7 to 22 0/7 weeks of gestation
* Maternal age ≥ 18 yrs
* Cervical length less than 38 mm
* Informed consent
* Not participating in another PTB study at the same time

Exclusion Criteria:

To be eligible for enrolment in this study each subject must not meet any of the following criteria:

* History of cervical surgery
* Cervical cerclage in place
* Twin-to-twin transfusion syndrome
* Stillbirth or major congenital abnormalities in any of the fetus
* Severe vaginal discharge, acute vaginitis
* Premature rupture of membranes
* Premature labor

Primary outcomes:
measure: Preterm birth before 34 weeks of gestation
timeFrame: At birth
Secondary outcomes:
measure: Intrauterine death before 24 weeks of gestation
timeFrame: From randomisation to 24 weeks
measure: Stillbirth
timeFrame: At birth
measure: Delivery before 24 weeks of gestation
timeFrame: At birth
measure: Delivery before 28 weeks of gestation
timeFrame: At birth
measure: Delivery before 32 weeks of gestation
timeFrame: At birth
measure: Delivery before 37 weeks of gestation
timeFrame: At birth
measure: Labour induction
timeFrame: At birth
measure: Prelabour rupture of membrane
timeFrame: From randomization to less than 37 weeks
measure: Mode of delivery
timeFrame: At birth
measure: Livebirth at any gestational age
timeFrame: At birth
measure: Use of tocolytics drug
timeFrame: From 24 weeks to 34 weeks
measure: Use of corticosteroids
timeFrame: From 24 weeks to 34 weeks
measure: Admission days for preterm labor
timeFrame: From 24 weeks to 37 week
measure: Choriamnionitis
timeFrame: From randomization to birth
measure: Maternal morbidity
timeFrame: From randomization to birth
measure: Birthweight
timeFrame: At birth
measure: Birthweight < 1500g
timeFrame: At birth
measure: Birthweight < 2500g
timeFrame: At birth
measure: Congenital anomalies
timeFrame: At birth
measure: 5-minute Apgar score
timeFrame: At birth
measure: 5-minute Apgar score < 7
timeFrame: At birth
measure: Admission to NICU
timeFrame: Within 7 days after delivery
measure: Length of NICU admission
timeFrame: Up to 28 days after birth
measure: Severe respiratory distress syndrome
timeFrame: Within 24 hours after delivery
measure: Bronchopulmonary dysplasia
timeFrame: At time of discharge home or at 36 weeks of gestational age
measure: Intraventricular haemorrhage
timeFrame: Up to 28 days after birth
measure: Necrotising enterocolitis
timeFrame: Up to 28 days after birth
measure: Proven sepsis
timeFrame: Up to 28 days after birth
measure: Death before discharge
timeFrame: Up to 28 days after birth
measure: Maternal side effects
timeFrame: From randomisation to birth
measure: Withdrawal from treatment
timeFrame: From randomization to 36 weeks of gestation
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital
state: Tan Binh District
Study officials:
affiliation: Research Center for Genetics and Reproductive Health
name: Tuong M Ho, MD
role: STUDY_DIRECTOR
References:
citation: Dang VQ, Nguyen LK, Pham TD, He YTN, Vu KN, Phan MTN, Le TQ, Le CH, Vuong LN, Mol BW. Pessary Compared With Vaginal Progesterone for the Prevention of Preterm Birth in Women With Twin Pregnancies and Cervical Length Less Than 38 mm: A Randomized Controlled Trial. Obstet Gynecol. 2019 Mar;133(3):459-467. doi: 10.1097/AOG.0000000000003136.