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| Name | Class |
|---|---|
| My Duc Phu Nhuan Hospital HCMC, Vietnam | UNKNOWN |
| Quang Ninh Obstetrics and Pediatrics Hospital, Quang Ninh, Vietnam | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cervical pessary | Device | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of preterm birth <37 weeks of gestation by any cause | Birth before 37 weeks | From date of randomisation until 36 6/7 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Gestational age at delivery | Gestational age at delivery | At birth |
| Time from randomization to delivery | Time interval between randomisation and delivery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Vinh Q Dang, MD | Contact | +84908225481 | bsvinh.dq@myduchospital.vn | |
| Minh N Chau, MD | Contact | +84903119996 | bsminh.cn@myduchospital.vn |
| Name | Affiliation | Role |
|---|---|---|
| Vinh Q Dang, MD | Mỹ Đức Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| My Duc Phu Nhuan Hospital | Recruiting | Ho Chi Minh City | Phu Nhuan | Vietnam |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22682464 | Background | 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. | |
| 24794180 |
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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Participants will be randomised to either pessary or progesterone in a 1:1 ratio with a variable block size of 2, 4 or 6.
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|
| Vaginal Progesterone | Drug | 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. |
|
|
| From date of randomisation until the date of delivery. |
| Rate of preterm birth before 28 weeks of gestation | Birth before 28 weeks | From date of randomisation until 27 6/7 weeks |
| Rate of preterm birth before 34 weeks of gestation | Birth before 34 weeks | 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) | 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) | 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) | From date of randomisation until 36 6/7 weeks |
| Rate of iatrogenic preterm birth <28 weeks | Birth non-spontaneously before 28 weeks' gestation | From date of randomisation until 27 6/7 weeks |
| Rate of iatrogenic preterm birth <34 weeks | Birth non-spontaneously before 34 weeks' gestation | From date of randomisation until 33 6/7 weeks |
| Rate of iatrogenic preterm birth <37 weeks | Birth non-spontaneously before 37 weeks' gestation | From date of randomisation until 36 6/7 weeks |
| Rate of onset of labor | Spontaneous, labor induction, elective C-section | At birth |
| Rate of modes of delivery | Vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor) | 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 | At birth |
| Rate of use of tocolytic drugs | Use of any tocolytic drug to treat preterm labour | 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 | From 24 0/7 to 36 6/7 weeks' gestation |
| Rate of use of MgSO4 for neuroprotection | Use of MgSO4 for neuroprotection | 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 | 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 | From randomization to 37 week |
| Rate of chorioamnionitis | Intraamniotic infection | From randomization to delivery, up to 28 weeks |
| Rate of maternal mortality | Death of the mother | From randomization to delivery, up to 28 weeks |
| Birthweight (mean) | Weight of baby born | At birth |
| Birthweight <1500 g | Weight of baby born <1500g | At birth |
| Birthweight <2500 g | Weight of baby born <2500g | At birth |
| Rate of congenital anomalies | Any congenital anomalies detected in baby born | 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. | At birth |
| 5-min Apgar score <7 | Apgar score at 5 minute after birth <7. An increased relative risk of cerebral palsy. | At birth |
| Rate of admission to neonatal intensive care unit (NICU) | Admission to neonatal intensive care unit of baby | Up to 28 days of life after the due day |
| Length of NICU admission | Number of admission days to NICU | Up to 28 days of life after the due day |
| Rate of death before discharge | Death of newborn before discharge from nursery | 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 | 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 | 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 | 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 | 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 | 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 | Up to 28 days of life after the due day |
| Rate of necrotizing enterocolitis | Diagnosed according to Bell | Up to 28 days of life after the due day |
| Rate of proven sepsis | The combination of clinical signs and positive blood cultures | 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) | 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. | 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 | 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 | From date of randomisation until delivery, which is up to 24 weeks |
| Mỹ Đức Hospital | Recruiting | Ho Chi Minh City | Tan Binh | Vietnam |
|
| Quang Ninh Obstetrics and Pediatrics Hospital | Recruiting | Quang Ninh | Vietnam |
|
| Platt 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. |
| 24625252 | Background | Lawn 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. |
| 29779863 | Background | Vogel 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. |
| 27133011 | Background | Society 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. |
| 16308894 | Background | Leung 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. |
| 22284156 | Background | Romero 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. |
| 21472815 | Background | Hassan 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. |
| 26921136 | Background | Norman 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. |
| 29157866 | Background | Romero 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. |
| 12747228 | Background | Arabin 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. |
| 26627728 | Background | Goya 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. |
| 23924878 | Background | Liem 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. |
| 30741812 | Background | 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. |
| 29103351 | Background | Jin 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. |
| 28398701 | Background | Saccone G, Ciardulli A, Xodo S, Dugoff L, Ludmir J, Pagani G, Visentin S, Gizzo S, Volpe N, Maruotti GM, Rizzo G, Martinelli P, Berghella V. Cervical Pessary for Preventing Preterm Birth in Singleton Pregnancies With Short Cervical Length: A Systematic Review and Meta-analysis. J Ultrasound Med. 2017 Aug;36(8):1535-1543. doi: 10.7863/ultra.16.08054. Epub 2017 Apr 11. |
| D000091642 | Urogenital Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045167 | Progesterone Congeners |
| D012739 | Gonadal Steroid Hormones |