Progesterone and Cervical Pessary in Twins

NCT ID: NCT03058536

Last Updated: 2017-03-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

312 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-21

Study Completion Date

2019-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The aim of this randomized control trial is to determine wheter cervical pessary plus vaginal progesterone (400mg) reduce preterm birth less than 34 weeks of gestacion and improve perinatal outcome, among women presenting asyntomatic short cervix, in twin pregnancy.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The frequency of twin pregnancies has increased significantly, especially because of the assisted reproduction and advanced maternal age at conception. The twin pregnancies are responsible for 25 % of all preterm birth. Consequently, twin pregnancies are more associated with perinatal mortality and morbidity when compared to single pregnancies. Additionally, the short cervix (\< 25 mm) in singleton and twin pregnancies are associated with significantly increased preterm birth.

Randomized controlled trials in singleton pregnancies reported that profilatic cervical cerclage and vaginal progesterone reduce significantly the rate of early preterm birth. In twin pregnancies, vaginal progesterone and profilatic cerclage have been shown to be ineffective in prevention of preterm birth.

However, two individual pacient data meta-analyses reported in a subgroup of women with twin pregancies and short cervix, that vaginal progesterone reduce significantly adverse neonatal outcomes. Nowadays, the effet of cervical pessary is contraditory, mainly in women with short cervix.

This is a randomized prospective trial at São Paulo University Medical School. This trial will involve 312 women with twins pregnancies and short cervix between 16 and 27 weeks and 6 days of gestacional age. Women with twin pregnancy and short cervix ( defined according to the gestacional age ) will be assigned randomly to daily vaginal progesterone (400mg) combined with insertion of cervical pessary, isolated use of daily vaginal progesterone (400mg) isolated insertion of cervical pessary or expectant management (no intervention). The primary outcome is to compare the rate of spontaneous delivery \< 34 weeks of gestacion between groups.The secondary outcome is to compare the neonatal adverse outcome between the groups.

The aim of this study is to test the hypothesis that the insertion of a cervical pessary combined with vaginal progesterone, in twin pregnancies with short cervix would reduce the spontaneus preterm birth \< 34 weeks' gestation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Preterm Birth Twin Pregnancy With Antenatal Problem

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

312 twin pregnant women with short cervix between 16 and 27 weeks and 6 days of gestacional age will be randomized in four groups: daily 400mg vaginal progesterone combined with insertion of cervical pessary; isolated use of daily 400mg vaginal progesterone, isolated insertion of cervical pessary or expectant management (no intervention).
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Progesterone

400 mg micronized vaginal progesterone daily from randomization to 36 weeks

Group Type ACTIVE_COMPARATOR

Vaginal Progesterone

Intervention Type DRUG

Treatment with 400 mg micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.

Arabin Pessary and Progesterone

Arabin Pessary and Natural Micronized Progesterone

400 mg micronized vaginal progesterone daily from randomization to 36 weeks

The device will be placed at randomization and will be removed during the 36th week of gestacional (or earlier if indicated) in combination with vaginal progesterone.

Group Type ACTIVE_COMPARATOR

Arabin Pessary and Progesterone

Intervention Type OTHER

Arabin Pessary and Progesterone The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner. Treatment with 400 mg Micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.

Arabin Pessary

The device will be placed at randomization and will be removed during the 36th week of gestacional (or earlier if indicated) without vaginal progesterone use.

Group Type ACTIVE_COMPARATOR

Arabin Pessary

Intervention Type DEVICE

The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner.

No intervention

Expectant management

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Arabin Pessary

The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner.

Intervention Type DEVICE

Vaginal Progesterone

Treatment with 400 mg micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.

Intervention Type DRUG

Arabin Pessary and Progesterone

Arabin Pessary and Progesterone The cervical pessary will be inserted at the randomization and removed during the 36 week of pregnancy, unless labour occurs sooner. Treatment with 400 mg Micronized progesterone daily, until the day of randomization to 36 weeks of pregnancy.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Utrogestan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Twin pregnancy ( dichorionic or monochorionic diamniotic)
* Both fetuses alive
* Asymptomatic short cervix according to gestational age ( measurement less or equal 30 mm between 16 weeks + 0 day and 22 weeks + 0 day, less or equal 25 mm between 22 weeks + 1 day and 24 weeks + 0 day and less or equal 20 mm between 24 weeks + 1 day and 27 weeks + 6 days)
* Gestational age between 16 to 27weeks and 6 days
* Intact membranes
* Informed consent

Exclusion Criteria

* Monoamniotic twins
* Twin Twin transfusion syndrome
* Rupture membranes
* Major malformation or chromosomal abnormality at least one fetus
* Women with Cervical cerclage in the current pregnancy
* Ballooning of membranes outside the cervix into the vagina
* Placenta previa
* Treatment with progesterone before randomization
* Allergy of the excipientes of the micronized progesterone
* Labor
* Severe hepatic disfunction, porphyria, otosclerosis, severe depression
* Use of drugs that interfere the effects of progesterone
Minimum Eligible Age

16 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Mario Henrique Burlacchini de Carvalho

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mario Henrique Burlacchini de Carvalho

Professor Doutor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mario Henrique Burlacchini de Carvalho, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital das Clínicas Universidade de São Paulo

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hospital das Clinicas da FMUSP

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Brazil

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Mario Henrique Burlacchini de Carvalho, PhD

Role: CONTACT

+55 11 26616209 ext. 3183

Carolina Fiuza Branco

Role: CONTACT

+55 11 986974207

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Mario Henrique Burlacchini de Carvalho, PhD

Role: primary

551126616209

References

Explore related publications, articles, or registry entries linked to this study.

Kindinger LM, Poon LC, Cacciatore S, MacIntyre DA, Fox NS, Schuit E, Mol BW, Liem S, Lim AC, Serra V, Perales A, Hermans F, Darzi A, Bennett P, Nicolaides KH, Teoh TG. The effect of gestational age and cervical length measurements in the prediction of spontaneous preterm birth in twin pregnancies: an individual patient level meta-analysis. BJOG. 2016 May;123(6):877-84. doi: 10.1111/1471-0528.13575. Epub 2015 Sep 1.

Reference Type BACKGROUND
PMID: 26333191 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22284156 (View on PubMed)

Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K, Cooper S, Calder A, Mires G, Danielian P, Sturgiss S, MacLennan G, Tydeman G, Thornton S, Martin B, Thornton JG, Neilson JP, Norrie J. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009 Jun 13;373(9680):2034-40. doi: 10.1016/S0140-6736(09)60947-8.

Reference Type BACKGROUND
PMID: 19523680 (View on PubMed)

Brizot ML, Hernandez W, Liao AW, Bittar RE, Francisco RPV, Krebs VLJ, Zugaib M. Vaginal progesterone for the prevention of preterm birth in twin gestations: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2015 Jul;213(1):82.e1-82.e9. doi: 10.1016/j.ajog.2015.02.021. Epub 2015 Feb 27.

Reference Type BACKGROUND
PMID: 25731690 (View on PubMed)

Schuit E, Stock S, Rode L, Rouse DJ, Lim AC, Norman JE, Nassar AH, Serra V, Combs CA, Vayssiere C, Aboulghar MM, Wood S, Cetingoz E, Briery CM, Fonseca EB, Worda K, Tabor A, Thom EA, Caritis SN, Awwad J, Usta IM, Perales A, Meseguer J, Maurel K, Garite T, Aboulghar MA, Amin YM, Ross S, Cam C, Karateke A, Morrison JC, Magann EF, Nicolaides KH, Zuithoff NP, Groenwold RH, Moons KG, Kwee A, Mol BW; Global Obstetrics Network (GONet) collaboration. Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis. BJOG. 2015 Jan;122(1):27-37. doi: 10.1111/1471-0528.13032. Epub 2014 Aug 22.

Reference Type BACKGROUND
PMID: 25145491 (View on PubMed)

Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A; PREDICT Group. Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet Gynecol. 2011 Sep;38(3):272-80. doi: 10.1002/uog.9093.

Reference Type BACKGROUND
PMID: 21739497 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26627728 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23924878 (View on PubMed)

Fox NS, Gupta S, Lam-Rachlin J, Rebarber A, Klauser CK, Saltzman DH. Cervical Pessary and Vaginal Progesterone in Twin Pregnancies With a Short Cervix. Obstet Gynecol. 2016 Apr;127(4):625-630. doi: 10.1097/AOG.0000000000001300.

Reference Type BACKGROUND
PMID: 26959202 (View on PubMed)

Nicolaides KH, Syngelaki A, Poon LC, de Paco Matallana C, Plasencia W, Molina FS, Picciarelli G, Tul N, Celik E, Lau TK, Conturso R. Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: a randomized controlled trial. Am J Obstet Gynecol. 2016 Jan;214(1):3.e1-9. doi: 10.1016/j.ajog.2015.08.051. Epub 2015 Aug 28.

Reference Type BACKGROUND
PMID: 26321037 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1.847.411

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.