Cervical Pessary vs. Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies

Pregnancy Clinical Trial

Official title:

The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies: a Randomized Controlled Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02623881
• Other study ID #: NCKH/CGRH_10_2015
• Status: Completed
• Phase: N/A
• First received: November 30, 2015
• Last updated: December 21, 2017
• Start date: March 4, 2016
• Est. completion date: November 2, 2017

Study information

• Verified date: December 2017
• Source: Vietnam National University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: November 2, 2017
• Est. primary completion date: November 2, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pregnancy
• Premature Birth

Intervention

Device:
• Cervical pessary
Arabin (cervical pessary) will be inserted at 16-22 weeks and removed at 36 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort

Drug:
• Vaginal progesterone
Vaginal progesterone (Cyclogest 400 mg) once a day will be used, from 16-22 to 36 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort

Locations

Country	Name	City	State
Vietnam	My Duc Hospital	Ho Chi Minh City	Tan Binh District

Sponsors (2)

Lead Sponsor	Collaborator
Vietnam National University	M? Ð?c Hospital

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm birth before 34 weeks of gestation	Birth before 34 weeks	At birth
Secondary	Intrauterine death before 24 weeks of gestation	Death of any fetus intrauterine before 24 weeks	From randomisation to 24 weeks
Secondary	Stillbirth	Baby born with no signs of life at or after 28 weeks	At birth
Secondary	Delivery before 24 weeks of gestation	Birth before 24 weeks	At birth
Secondary	Delivery before 28 weeks of gestation	Birth before 28 weeks	At birth
Secondary	Delivery before 32 weeks of gestation	Birth before 32 weeks	At birth
Secondary	Delivery before 37 weeks of gestation	Birth before 37 weeks	At birth
Secondary	Labour induction	Labor initiated with a method such as oxytocin, Foley bulb, or artificial rupture of membranes.	At birth
Secondary	Prelabour rupture of membrane	Prelabour rupture of membranes and gestational age less than 37 weeks	From randomization to less than 37 weeks
Secondary	Mode of delivery	Spontaneous, forceps/ventouse, emergency C-section, planned C-section	At birth
Secondary	Livebirth at any gestational age	Birth of at least one newborn that exhibits any sign of life, such as respiration, heartbeat, umbilical pulsation or movement of voluntary muscles	At birth
Secondary	Use of tocolytics drug	Use of tocolytics drug to prevent premature labor	From 24 weeks to 34 weeks
Secondary	Use of corticosteroids	Use of corticosteroids to prevent respiratory distressed syndrome	From 24 weeks to 34 weeks
Secondary	Admission days for preterm labor	Days admission to hospital due to preterm labor	From 24 weeks to 37 week
Secondary	Choriamnionitis	Intraamniotic infection	From randomization to birth
Secondary	Maternal morbidity	Thromboembolic complications, urinary tract infection treated with antibiotics, pneumonia, endometritis, hypertension disorder, eclampsia or HELLP syndrome, or death	From randomization to birth
Secondary	Birthweight	Weight of babies	At birth
Secondary	Birthweight < 1500g	Weight of babies < 1500g	At birth
Secondary	Birthweight < 2500g	Weight of babies < 2500g	At birth
Secondary	Congenital anomalies	Congenital malformation of newborn	At birth
Secondary	5-minute Apgar score	Apgar score at 5 minute after birth	At birth
Secondary	5-minute Apgar score < 7	Apgar score < 7 at 5 minute after birth	At birth
Secondary	Admission to NICU	The admittance of newborn to NICU	Within 7 days after delivery
Secondary	Length of NICU admission	Number of days admittance of newborn to NICU	Up to 28 days after birth
Secondary	Severe respiratory distress syndrome	Grade 2 or worse, as diagnosed by Giedion et al	Within 24 hours after delivery
Secondary	Bronchopulmonary dysplasia	Diagnosed according to the international consensus guideline as described by Jobe and Bancalari	At time of discharge home or at 36 weeks of gestational age
Secondary	Intraventricular haemorrhage	Grade II B or worse, as diagnosed by repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al. and Ment et al	Up to 28 days after birth
Secondary	Necrotising enterocolitis	> stage 1, will be diagnosed according to Bell	Up to 28 days after birth
Secondary	Proven sepsis	The combination of clinical signs and positive blood cultures.	Up to 28 days after birth
Secondary	Death before discharge	Death of newborn before discharge from nursery	Up to 28 days after birth
Secondary	Maternal side effects	Vaginal discharge, fever, other signs of infections, pain, pessary repositioning and necrosis or rupture of the cervix	From randomisation to birth
Secondary	Withdrawal from treatment	Patient's discontinuation of arabin or vaginal progesterone use	From randomization to 36 weeks of gestation