Progesterone and Cervical Pessary in Twins

NCT03058536 | Unknown Phase 2 FDA Drug FDA Device

• 1 other identifier: 1.847.411
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Preterm Birth; Twin Pregnancy With Antenatal Problem

Keywords

twin short cervix pessary progesterone preterm birth

Outcome Measures

Primary Outcomes (1)

• Preterm birth

  Rate of preterm birth before 34 weeks gestation

  5 months

Secondary Outcomes (2)

• Neonatal Complications Rate

  between birth and 28 days of age

• Months from Randomization to delivery interval

  6 months

Study Arms (4)

Progesterone

ACTIVE COMPARATOR

400 mg micronized vaginal progesterone daily from randomization to 36 weeks

Drug: Vaginal Progesterone

Arabin Pessary and Progesterone

ACTIVE COMPARATOR

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.

Other: Arabin Pessary and Progesterone

Arabin Pessary

ACTIVE COMPARATOR

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.

Device: Arabin Pessary

No intervention

NO INTERVENTION

Expectant management

Interventions

Arabin Pessary DEVICE

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

Arabin Pessary

Vaginal Progesterone DRUG

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

Also known as: Utrogestan

Progesterone

Arabin Pessary and Progesterone 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 and Progesterone

Eligibility Criteria

• Age: 16 Years - 50 Years
• Gender Eligibility Details: pregnant women
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Henrique Burlacchini de Carvalho: lead

Study Sites (1)

Hospital das Clinicas da FMUSP

São Paulo, São Paulo, Brazil

RECRUITING

Related Publications (10)

• 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.

  PMID: 26333191 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.

  PMID: 22284156 BACKGROUND

• 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.

  PMID: 19523680 BACKGROUND

• 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.

  PMID: 25731690 BACKGROUND

• 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.

  PMID: 25145491 BACKGROUND

• 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.

  PMID: 21739497 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.

  PMID: 26627728 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.

  PMID: 23924878 BACKGROUND

• 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.

  PMID: 26959202 BACKGROUND

• 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.

  PMID: 26321037 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Interventions

Utrogestan; Progesterone

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Mario Henrique Burlacchini de Carvalho, PhD

  Hospital das Clínicas Universidade de São Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mario Henrique Burlacchini de Carvalho, PhD

CONTACT

+55 11 26616209; mario.burlacchini@hc.fm.usp.br

Carolina Fiuza Branco

CONTACT

+55 11 986974207; carolfiuzabranco@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Doutor

Model Details: 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).

Study Record Dates

• First Submitted: February 5, 2017
• First Posted: February 23, 2017
• Study Start: February 21, 2017
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 15, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)