Preterm BirthNCT04300322
Pessary Versus Progesterone in Singletons
A study testing Cervical pessary and Vaginal Progesterone in people with Preterm Birth and Short Cervix, run by Mỹ Đức Hospital at 3 sites in Vietnam.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Birth, Short Cervix
- 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
- 804 participants
- Where
- 3 sitesVietnam
- Study dates
- 1 May 2020to 1 Dec 2022
- 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
- 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.
Who cannot join
- 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
Show all 10Show fewer
- Premature labor without ruptured membrane at the time of screening
- Suspected chorioamnionitis
- Unable to have cervical pessary inserted
- Cerclage or pessary in place
Trial locations and contacts
3 sites in 1 country.
Vietnam3 sites, 3 recruiting
- Recruiting
My Duc Phu Nhuan Hospital
Ho Chi Minh City, Phu Nhuan
Khang N Vu, MD, 0983813006, bskhang.vn@myduchospital.vn
- Recruiting
Mỹ Đức Hospital
Ho Chi Minh City, Tan Binh
Minh N Chau, MD, +84903119996, bsminh.cn@myduchospital.vn
- Recruiting
Quang Ninh Obstetrics and Pediatrics Hospital
Quang Ninh
Long D Do, MD, 0912388576, longbacsi@gmail.com
About this study
Official title: The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for the Prevention of Preterm Birth in Women With Singleton Pregnancies and Short Cervix: a Multicenter Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Preterm Birth, Short Cervix
- Being tested
- Cervical pessary, Vaginal Progesterone
- Keywords
- Preterm Birth, Singleton Pregnancies, Short Cervix, Pessary, Progesterone
- 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 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort
Vaginal ProgesteroneDrug
Also called Cyclogest 200 mg
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.
| 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 37 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 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. Receives: Drug: Vaginal Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of preterm birth <37 weeks of gestation by any cause
Birth before 37 weeks
Measured: From date of randomisation until 36 6/7 weeks
Secondary outcomes (41)
Gestational age at delivery
Gestational age at delivery
Measured: At birth
Time from randomization to delivery
Time interval between randomisation and delivery
Measured: From date of randomisation until the date of delivery.
Rate of preterm birth before 28 weeks of gestation
Birth before 28 weeks
Measured: From date of randomisation until 27 6/7 weeks
Rate of preterm birth before 34 weeks of gestation
Birth before 34 weeks
Measured: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <28 weeks
Birth spontaneously before 28 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Measured: From date of randomisation until 27 6/7 weeks
Rate of spontaneous preterm birth <34 weeks
Birth spontaneously before 34 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Measured: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <37 weeks
Birth spontaneously before 37 weeks' gestation, including preterm spontaneous rupture of membranes, preterm premature rupture of membranes (PPROM)
Measured: From date of randomisation until 36 6/7 weeks
Rate of iatrogenic preterm birth <28 weeks
Birth non-spontaneously before 28 weeks' gestation
Measured: From date of randomisation until 27 6/7 weeks
Rate of iatrogenic preterm birth <34 weeks
Birth non-spontaneously before 34 weeks' gestation
Measured: From date of randomisation until 33 6/7 weeks
Rate of iatrogenic preterm birth <37 weeks
Birth non-spontaneously before 37 weeks' gestation
Measured: From date of randomisation until 36 6/7 weeks
Rate of onset of labor
Spontaneous, labor induction, elective C-section
Measured: At birth
Rate of modes of delivery
Vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor)
Measured: At birth
Rate of all live births at any gestational age
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
Measured: At birth
Rate of use of tocolytic drugs
Use of any tocolytic drug to treat preterm labour
Measured: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of antenatal corticosteroids
Use of antenatal corticosteroids to prevent respiratory distressed syndrome
Measured: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of MgSO4 for neuroprotection
Use of MgSO4 for neuroprotection
Measured: From 28 0/7 to 31 6/7 weeks' gestation
Rate of preterm premature rupture of membranes
Prelabour rupture of membranes and gestational age less than 37 weeks
Measured: From randomization to less than 37 weeks, up to 21 weeks
Length of maternal admission for preterm labor (days)
Number of admission days for treatment of preterm labour
Measured: From randomization to 37 week
Rate of chorioamnionitis
Intraamniotic infection
Measured: From randomization to delivery, up to 28 weeks
Rate of maternal mortality
Death of the mother
Measured: From randomization to delivery, up to 28 weeks
Birthweight (mean)
Weight of baby born
Measured: At birth
Birthweight <1500 g
Weight of baby born <1500g
Measured: At birth
Birthweight <2500 g
Weight of baby born <2500g
Measured: At birth
Rate of congenital anomalies
Any congenital anomalies detected in baby born
Measured: At birth
5-min Apgar score
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.
Measured: At birth
5-min Apgar score <7
Apgar score at 5 minute after birth <7. An increased relative risk of cerebral palsy.
Measured: At birth
Rate of admission to neonatal intensive care unit (NICU)
Admission to neonatal intensive care unit of baby
Measured: Up to 28 days of life after the due day
Length of NICU admission
Number of admission days to NICU
Measured: Up to 28 days of life after the due day
Rate of death before discharge
Death of newborn before discharge from nursery
Measured: Up to 28 days of life after the due day
Rate of neonatal death
Death of a live-born infant within the first 28 days of life after the due day
Measured: Up to 28 days of life after the due day
Rate of perinatal death
Intrauterine fetal death after 20 weeks of gestation, or neonatal death
Measured: After 20 weeks of gestation to 28 days of life after the due day
Rate of stillbirth
Baby born with no signs of life at or after 20 weeks' gestation
Measured: After 20 weeks of gestation until the date of delivery
Rate of composite of poor perinatal outcomes
Foetal or neonatal death, intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis
Measured: Up to 28 days of life after the due day
Rate of respiratory distress syndrome
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
Measured: Up to 28 days of life after the due day
Rate of periventricular haemorrhage II B or worse
Repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al
Measured: Up to 28 days of life after the due day
Rate of necrotizing enterocolitis
Diagnosed according to Bell
Measured: Up to 28 days of life after the due day
Rate of proven sepsis
The combination of clinical signs and positive blood cultures
Measured: Up to 28 days of life after the due day
Rate of maternal vaginal side effects
Including vaginal discharge, vaginal bleeding, vaginal infection (confirmed by vaginal discharge culture)
Measured: From date of randomisation until delivery, which is up to 24 weeks
Vaginal pain Score
Evaluated by VAS numerical rating scale. Assessments with units on a Scale.
Measured: From date of randomisation until delivery, which is up to 24 weeks
Rate of pessary repositioning
After pessary initial placement, requiring to reposition the pessary by any reasons
Measured: From date of randomisation until delivery, which is up to 24 weeks
Rate of maternal cervical side effects
Including necrosis or rupture of the cervix, cervical laceration
Measured: From date of randomisation until delivery, which is up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2020
- Study start1 May 2020
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 804 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- My Duc Phu Nhuan Hospital HCMC, Vietnam, Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam
- Responsible party
- Sponsor
- Investigators
- Vinh Q Dang, MD, Principal investigator, Mỹ Đức Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04300322
- Sponsor's protocol ID
- CS/BVMD/20/04
- Status last verified
- Oct 2020
- First submitted
- 28 Feb 2020
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4.
PubMed 22682464Platt MJ. Outcomes in preterm infants. Public Health. 2014 May;128(5):399-403. doi: 10.1016/j.puhe.2014.03.010. Epub 2014 May 1.
PubMed 24794180Lawn JE, Kinney MV, Belizan JM, Mason EM, McDougall L, Larson J, Lackritz E, Friberg IK, Howson CP; Born Too Soon Preterm Birth Action Group. Born too soon: accelerating actions for prevention and care of 15 million newborns born too soon. Reprod Health. 2013;10 Suppl 1(Suppl 1):S6. doi: 10.1186/1742-4755-10-S1-S6. Epub 2013 Nov 15.
PubMed 24625252Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Pract Res Clin Obstet Gynaecol. 2018 Oct;52:3-12. doi: 10.1016/j.bpobgyn.2018.04.003. Epub 2018 Apr 26.
PubMed 29779863Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; McIntosh J, Feltovich H, Berghella V, Manuck T. The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention. Am J Obstet Gynecol. 2016 Sep;215(3):B2-7. doi: 10.1016/j.ajog.2016.04.027. Epub 2016 Apr 28.
PubMed 27133011Leung TN, Pang MW, Leung TY, Poon CF, Wong SM, Lau TK. Cervical length at 18-22 weeks of gestation for prediction of spontaneous preterm delivery in Hong Kong Chinese women. Ultrasound Obstet Gynecol. 2005 Dec;26(7):713-7. doi: 10.1002/uog.2617.
PubMed 16308894Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11.
PubMed 22284156Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
PubMed 21472815Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR, Thornton S, Robson SC, McConnachie A, Petrou S, Sebire NJ, Lavender T, Whyte S, Norrie J; OPPTIMUM study group. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016 May 21;387(10033):2106-2116. doi: 10.1016/S0140-6736(16)00350-0. Epub 2016 Feb 24.
PubMed 26921136Romero R, Conde-Agudelo A, Da Fonseca E, O'Brien JM, Cetingoz E, Creasy GW, Hassan SS, Nicolaides KH. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data. Am J Obstet Gynecol. 2018 Feb;218(2):161-180. doi: 10.1016/j.ajog.2017.11.576. Epub 2017 Nov 17.
PubMed 29157866Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.
PubMed 12747228Goya M, de la Calle M, Pratcorona L, Merced C, Rodo C, Munoz B, Juan M, Serrano A, Llurba E, Higueras T, Carreras E, Cabero L; PECEP-Twins Trial Group. Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins). Am J Obstet Gynecol. 2016 Feb;214(2):145-152. doi: 10.1016/j.ajog.2015.11.012. Epub 2015 Nov 25.
PubMed 26627728Liem S, Schuit E, Hegeman M, Bais J, de Boer K, Bloemenkamp K, Brons J, Duvekot H, Bijvank BN, Franssen M, Gaugler I, de Graaf I, Oudijk M, Papatsonis D, Pernet P, Porath M, Scheepers L, Sikkema M, Sporken J, Visser H, van Wijngaarden W, Woiski M, van Pampus M, Mol BW, Bekedam D. Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial. Lancet. 2013 Oct 19;382(9901):1341-9. doi: 10.1016/S0140-6736(13)61408-7. Epub 2013 Aug 5.
PubMed 23924878Dang 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 30741812Jin Z, Chen L, Qiao D, Tiwari A, Jaunky CD, Sun B, Wang L, Yu H. Cervical pessary for preventing preterm birth: a meta-analysis. J Matern Fetal Neonatal Med. 2019 Apr;32(7):1148-1154. doi: 10.1080/14767058.2017.1401998. Epub 2017 Nov 20.
PubMed 29103351
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Cervical Pessary Versus Vaginal Progesterone for the Prevention of Preterm Birth in Women With Singleton Pregnancies and Short Cervix: a Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04300322
- Acronym / sponsor ID
- CS/BVMD/20/04
- Conditions
- Preterm Birth, Short Cervix
- Keywords
- Preterm Birth, Singleton Pregnancies, Short Cervix, Pessary, Progesterone
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 804 participants (estimated)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Collaborators
- My Duc Phu Nhuan Hospital HCMC, Vietnam, Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam
- Study start
- 1 May 2020 (actual)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 9 Mar 2020 (actual)
- 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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cervical pessary | Active comparator | Device: Cervical pessaryCervical pessary (Arabin) will be inserted to participants 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. |
| Vaginal Progesterone | Active comparator | Drug: Vaginal ProgesteroneVaginal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
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 37 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 200 mgVaginal 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. | Drug | Vaginal Progesterone |
Primary outcome
Rate of preterm birth <37 weeks of gestation by any cause
Time frame: From date of randomisation until 36 6/7 weeks
Birth before 37 weeks
41 secondary outcomes
Gestational age at delivery
Time frame: At birth
Time from randomization to delivery
Time frame: From date of randomisation until the date of delivery.
Rate of preterm birth before 28 weeks of gestation
Time frame: From date of randomisation until 27 6/7 weeks
Rate of preterm birth before 34 weeks of gestation
Time frame: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <28 weeks
Time frame: From date of randomisation until 27 6/7 weeks
Rate of spontaneous preterm birth <34 weeks
Time frame: From date of randomisation until 33 6/7 weeks
Rate of spontaneous preterm birth <37 weeks
Time frame: From date of randomisation until 36 6/7 weeks
Rate of iatrogenic preterm birth <28 weeks
Time frame: From date of randomisation until 27 6/7 weeks
Rate of iatrogenic preterm birth <34 weeks
Time frame: From date of randomisation until 33 6/7 weeks
Rate of iatrogenic preterm birth <37 weeks
Time frame: From date of randomisation until 36 6/7 weeks
Rate of onset of labor
Time frame: At birth
Rate of modes of delivery
Time frame: At birth
Rate of all live births at any gestational age
Time frame: At birth
Rate of use of tocolytic drugs
Time frame: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of antenatal corticosteroids
Time frame: From 24 0/7 to 36 6/7 weeks' gestation
Rate of use of MgSO4 for neuroprotection
Time frame: From 28 0/7 to 31 6/7 weeks' gestation
Rate of preterm premature rupture of membranes
Time frame: From randomization to less than 37 weeks, up to 21 weeks
Length of maternal admission for preterm labor (days)
Time frame: From randomization to 37 week
Rate of chorioamnionitis
Time frame: From randomization to delivery, up to 28 weeks
Rate of maternal mortality
Time frame: From randomization to delivery, up to 28 weeks
Birthweight (mean)
Time frame: At birth
Birthweight <1500 g
Time frame: At birth
Birthweight <2500 g
Time frame: At birth
Rate of congenital anomalies
Time frame: At birth
5-min Apgar score
Time frame: At birth
5-min Apgar score <7
Time frame: At birth
Rate of admission to neonatal intensive care unit (NICU)
Time frame: Up to 28 days of life after the due day
Length of NICU admission
Time frame: Up to 28 days of life after the due day
Rate of death before discharge
Time frame: Up to 28 days of life after the due day
Rate of neonatal death
Time frame: Up to 28 days of life after the due day
Rate of perinatal death
Time frame: After 20 weeks of gestation to 28 days of life after the due day
Rate of stillbirth
Time frame: After 20 weeks of gestation until the date of delivery
Rate of composite of poor perinatal outcomes
Time frame: Up to 28 days of life after the due day
Rate of respiratory distress syndrome
Time frame: Up to 28 days of life after the due day
Rate of periventricular haemorrhage II B or worse
Time frame: Up to 28 days of life after the due day
Rate of necrotizing enterocolitis
Time frame: Up to 28 days of life after the due day
Rate of proven sepsis
Time frame: Up to 28 days of life after the due day
Rate of maternal vaginal side effects
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Vaginal pain Score
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Rate of pessary repositioning
Time frame: From date of randomisation until delivery, which is up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Background: PubMed 22682464Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4.
- Background: PubMed 24794180Platt MJ. Outcomes in preterm infants. Public Health. 2014 May;128(5):399-403. doi: 10.1016/j.puhe.2014.03.010. Epub 2014 May 1.
- Background: PubMed 24625252Lawn JE, Kinney MV, Belizan JM, Mason EM, McDougall L, Larson J, Lackritz E, Friberg IK, Howson CP; Born Too Soon Preterm Birth Action Group. Born too soon: accelerating actions for prevention and care of 15 million newborns born too soon. Reprod Health. 2013;10 Suppl 1(Suppl 1):S6. doi: 10.1186/1742-4755-10-S1-S6. Epub 2013 Nov 15.
- Background: PubMed 29779863Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Pract Res Clin Obstet Gynaecol. 2018 Oct;52:3-12. doi: 10.1016/j.bpobgyn.2018.04.003. Epub 2018 Apr 26.
- Background: PubMed 27133011Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; McIntosh J, Feltovich H, Berghella V, Manuck T. The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention. Am J Obstet Gynecol. 2016 Sep;215(3):B2-7. doi: 10.1016/j.ajog.2016.04.027. Epub 2016 Apr 28.
- Background: PubMed 16308894Leung TN, Pang MW, Leung TY, Poon CF, Wong SM, Lau TK. Cervical length at 18-22 weeks of gestation for prediction of spontaneous preterm delivery in Hong Kong Chinese women. Ultrasound Obstet Gynecol. 2005 Dec;26(7):713-7. doi: 10.1002/uog.2617.
- Background: PubMed 22284156Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19. doi: 10.1016/j.ajog.2011.12.003. Epub 2011 Dec 11.
- Background: PubMed 21472815Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
- Background: PubMed 26921136Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR, Thornton S, Robson SC, McConnachie A, Petrou S, Sebire NJ, Lavender T, Whyte S, Norrie J; OPPTIMUM study group. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016 May 21;387(10033):2106-2116. doi: 10.1016/S0140-6736(16)00350-0. Epub 2016 Feb 24.
- Background: PubMed 29157866Romero R, Conde-Agudelo A, Da Fonseca E, O'Brien JM, Cetingoz E, Creasy GW, Hassan SS, Nicolaides KH. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data. Am J Obstet Gynecol. 2018 Feb;218(2):161-180. doi: 10.1016/j.ajog.2017.11.576. Epub 2017 Nov 17.
- Background: PubMed 12747228Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.
- Background: PubMed 26627728Goya M, de la Calle M, Pratcorona L, Merced C, Rodo C, Munoz B, Juan M, Serrano A, Llurba E, Higueras T, Carreras E, Cabero L; PECEP-Twins Trial Group. Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins). Am J Obstet Gynecol. 2016 Feb;214(2):145-152. doi: 10.1016/j.ajog.2015.11.012. Epub 2015 Nov 25.
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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.
Vinh Q Dang, MD principal investigator
Mỹ Đức Hospital
3 sites 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 Preterm Birth and Short Cervix, run by Mỹ Đức Hospital at 3 sites 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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 9 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vinh Q Dang, MD (+84908225481, bsvinh.dq@myduchospital.vn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of preterm birth <37 weeks of gestation by any cause (time frame: From date of randomisation until 36 6/7 weeks). 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 NCT04300322, which also lists 16 linked publications.
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 9 Oct 2020.