PregnancyNCT02623881
Cervical Pessary vs. Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies
A study testing Cervical pessary and Vaginal progesterone in people with Pregnancy, run by Vietnam National University at 1 site in Vietnam.
Trial summary
To compare the effectiveness of cervical pessary (Arabin) and vaginal progesterone for preventing premature birth in twin pregnancies after IVF Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pregnancy
- What is being tested?
- Cervical pessary and Vaginal progesterone
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteVietnam
- Study dates
- 4 Mar 2016to 2 Nov 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies: a Randomized Controlled Trial.
To compare the effectiveness of cervical pessary (Arabin) and vaginal progesterone for preventing premature birth in twin pregnancies after IVF
Read the 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.
- Conditions
- Pregnancy
- Being tested
- Cervical pessary, Vaginal progesterone
- Keywords
- Cervical pessary, Vaginal progesterone, Twins, Premature birth
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cervical pessaryDevice
Also called Arabin
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
Vaginal progesteroneDrug
Also called Cyclogest 400mg
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
| Study group | Role | What they receive |
|---|---|---|
| Cervical pessary | Active comparator | Cervical pessary (Arabin) will be inserted to participants 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. Receives: Device: Cervical pessary |
| Vaginal Progesterone | Active comparator | 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. Receives: Drug: Vaginal progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preterm birth before 34 weeks of gestation
Birth before 34 weeks
Measured: At birth
Secondary outcomes (31)
Intrauterine death before 24 weeks of gestation
Death of any fetus intrauterine before 24 weeks
Measured: From randomisation to 24 weeks
Stillbirth
Baby born with no signs of life at or after 28 weeks
Measured: At birth
Delivery before 24 weeks of gestation
Birth before 24 weeks
Measured: At birth
Delivery before 28 weeks of gestation
Birth before 28 weeks
Measured: At birth
Delivery before 32 weeks of gestation
Birth before 32 weeks
Measured: At birth
Delivery before 37 weeks of gestation
Birth before 37 weeks
Measured: At birth
Labour induction
Labor initiated with a method such as oxytocin, Foley bulb, or artificial rupture of membranes.
Measured: At birth
Prelabour rupture of membrane
Prelabour rupture of membranes and gestational age less than 37 weeks
Measured: From randomization to less than 37 weeks
Mode of delivery
Spontaneous, forceps/ventouse, emergency C-section, planned C-section
Measured: At birth
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
Measured: At birth
Use of tocolytics drug
Use of tocolytics drug to prevent premature labor
Measured: From 24 weeks to 34 weeks
Use of corticosteroids
Use of corticosteroids to prevent respiratory distressed syndrome
Measured: From 24 weeks to 34 weeks
Admission days for preterm labor
Days admission to hospital due to preterm labor
Measured: From 24 weeks to 37 week
Choriamnionitis
Intraamniotic infection
Measured: From randomization to birth
Maternal morbidity
Thromboembolic complications, urinary tract infection treated with antibiotics, pneumonia, endometritis, hypertension disorder, eclampsia or HELLP syndrome, or death
Measured: From randomization to birth
Birthweight
Weight of babies
Measured: At birth
Birthweight < 1500g
Weight of babies < 1500g
Measured: At birth
Birthweight < 2500g
Weight of babies < 2500g
Measured: At birth
Congenital anomalies
Congenital malformation of newborn
Measured: At birth
5-minute Apgar score
Apgar score at 5 minute after birth
Measured: At birth
5-minute Apgar score < 7
Apgar score < 7 at 5 minute after birth
Measured: At birth
Admission to NICU
The admittance of newborn to NICU
Measured: Within 7 days after delivery
Length of NICU admission
Number of days admittance of newborn to NICU
Measured: Up to 28 days after birth
Severe respiratory distress syndrome
Grade 2 or worse, as diagnosed by Giedion et al
Measured: Within 24 hours after delivery
Bronchopulmonary dysplasia
Diagnosed according to the international consensus guideline as described by Jobe and Bancalari
Measured: At time of discharge home or at 36 weeks of gestational age
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
Measured: Up to 28 days after birth
Necrotising enterocolitis
> stage 1, will be diagnosed according to Bell
Measured: Up to 28 days after birth
Proven sepsis
The combination of clinical signs and positive blood cultures.
Measured: Up to 28 days after birth
Death before discharge
Death of newborn before discharge from nursery
Measured: Up to 28 days after birth
Maternal side effects
Vaginal discharge, fever, other signs of infections, pain, pessary repositioning and necrosis or rupture of the cervix
Measured: From randomisation to birth
Withdrawal from treatment
Patient's discontinuation of arabin or vaginal progesterone use
Measured: From randomization to 36 weeks of gestation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study start4 Mar 2016
- Primary completion2 Nov 2017
- Study completion2 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vietnam National University
- Sponsor type
- University, hospital or other
- Collaborators
- Mỹ Đức Hospital
- Responsible party
- Principal investigator, Manh Tuong Ho, Vietnam National University
- Investigators
- Tuong M Ho, MD, Study director, Research Center for Genetics and Reproductive Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02623881
- Sponsor's protocol ID
- NCKH/CGRH_10_2015
- Status last verified
- Dec 2017
- First submitted
- 30 Nov 2015
- Last updated
- 22 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30741812
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for Preventing Premature Birth in IVF Twin Pregnancies: a Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT02623881
- Acronym / sponsor ID
- NCKH/CGRH_10_2015
- Conditions
- Pregnancy
- Keywords
- Cervical pessary, Vaginal progesterone, Twins, Premature birth
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Vietnam National UniversityUniversity, hospital or other
- Collaborators
- Mỹ Đức Hospital
- Study start
- 4 Mar 2016 (actual)
- Primary completion
- 2 Nov 2017 (actual)
- Study completion
- 2 Nov 2017 (actual)
- First posted
- 8 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cervical pessary | Active comparator | Device: Cervical pessaryCervical pessary (Arabin) will be inserted to participants 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. |
| Vaginal Progesterone | Active comparator | Drug: Vaginal progesteroneVaginal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cervical pessaryAlso: ArabinArabin (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 | Device | Cervical pessary |
| Vaginal progesteroneAlso: Cyclogest 400mgVaginal 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 | Drug | Vaginal Progesterone |
Primary outcome
Preterm birth before 34 weeks of gestation
Time frame: At birth
Birth before 34 weeks
31 secondary outcomes
Intrauterine death before 24 weeks of gestation
Time frame: From randomisation to 24 weeks
Stillbirth
Time frame: At birth
Delivery before 24 weeks of gestation
Time frame: At birth
Delivery before 28 weeks of gestation
Time frame: At birth
Delivery before 32 weeks of gestation
Time frame: At birth
Delivery before 37 weeks of gestation
Time frame: At birth
Labour induction
Time frame: At birth
Prelabour rupture of membrane
Time frame: From randomization to less than 37 weeks
Mode of delivery
Time frame: At birth
Livebirth at any gestational age
Time frame: At birth
Use of tocolytics drug
Time frame: From 24 weeks to 34 weeks
Use of corticosteroids
Time frame: From 24 weeks to 34 weeks
Admission days for preterm labor
Time frame: From 24 weeks to 37 week
Choriamnionitis
Time frame: From randomization to birth
Maternal morbidity
Time frame: From randomization to birth
Birthweight
Time frame: At birth
Birthweight < 1500g
Time frame: At birth
Birthweight < 2500g
Time frame: At birth
Congenital anomalies
Time frame: At birth
5-minute Apgar score
Time frame: At birth
5-minute Apgar score < 7
Time frame: At birth
Admission to NICU
Time frame: Within 7 days after delivery
Length of NICU admission
Time frame: Up to 28 days after birth
Severe respiratory distress syndrome
Time frame: Within 24 hours after delivery
Bronchopulmonary dysplasia
Time frame: At time of discharge home or at 36 weeks of gestational age
Intraventricular haemorrhage
Time frame: Up to 28 days after birth
Necrotising enterocolitis
Time frame: Up to 28 days after birth
Proven sepsis
Time frame: Up to 28 days after birth
Death before discharge
Time frame: Up to 28 days after birth
Maternal side effects
Time frame: From randomisation to birth
Withdrawal from treatment
Time frame: From randomization to 36 weeks of gestation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
- Derived from this study: PubMed 30741812Dang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tuong M Ho, MD study director
Research Center for Genetics and Reproductive Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cervical pessary and Vaginal progesterone in people with Pregnancy, run by Vietnam National University at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preterm birth before 34 weeks of gestation (time frame: At birth). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02623881, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2017.