Comparing Double Dose of Vaginal Progesterone to no Treatment for Prevention of Preterm Birth in Twins and Short Cervix

Premature Birth Clinical Trial

Official title:

Comparing a Double Dose of Vaginal Progesterone to no Treatment for the Prevention of Preterm Birth in Twins Pregnancy and Short Cervix

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02329535
• Other study ID #: EMC-005413-CTIL
• Status: Terminated
• Phase: N/A
• First received: November 30, 2014
• Last updated: August 16, 2017
• Start date: January 2015
• Est. completion date: August 2017

Study information

• Verified date: August 2017
• Source: HaEmek Medical Center, Israel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Twin pregnancies are more likely to be delivered preterm than singleton pregnancies. Vaginal progesterone administration (200 mg Utrogestan) to asymptomatic women with a singleton pregnancy and sonographic short cervix reduced the risk of preterm birth (PTB) and neonatal morbidity and mortality, yet not proved efficient in twins' pregnancy. The investigators' hypothesis is that a higher dose of vaginal micronized progesterone will be more effective in preventing PTD. The objectives of the study is to compare the rate of preterm birth and perinatal morbidity and mortality in a twin pregnancy with short cervical length treated with vaginal 400 mg of micronized progesterone to no treatment. The study is Randomized, open label, of twin pregnancy between 16-26 weeks of gestation with cervical length under 25 mm. Women will be randomly assigned to either treatment or no treatment group. Progesterone treatment will be given until 36 weeks of gestation. Other management will be according to standard protocol.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Twin gestation

• Certain dating (documented first trimester ultrasound, or a reliable menstrual date confirmed by an ultrasound performed before 20 weeks of gestation)

• Age > 18 years

• Gestational age 16-26

• Cervical length<25 mm

• Intact membranes

• Informed consent

Exclusion Criteria:

• Major malformation or chromosomal abnormality to at least one fetus

• Higher order pregnancy

• Mocochorional-monoamniotic twin

• Death of one fetus

• Cervical dilatation >3 cm

• Chronic medical conditions that would interfere with study participation or evaluation of the treatment (e.g. seizures, psychiatric disorders, uncontrolled chronic hypertension, congestive heart failure, chronic renal failure, uncontrolled diabetes mellitus with end-organ dysfunction, active thrombophlebitis or a thromboembolic disorder, history of hormone-associated thrombophlebitis or thromboembolic disorders, active liver dysfunction or disease, known or suspected malignancy of the breast or genital organs)

Related Conditions & MeSH terms

• Premature Birth

Intervention

Drug:
• Micronized progesterone
vaginal caps 400 mg daily up to 36 weeks of gestation

Locations

Country	Name	City	State
Israel	Haemek Medical Center	Afula
Israel	The Nazareth hospital	Nazareth

Sponsors (1)

Lead Sponsor	Collaborator
HaEmek Medical Center, Israel

Country where clinical trial is conducted

Israel, 

References & Publications (8)

DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007 Oct;30(5):697-705. — View Citation

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. — View Citation

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. Review. — View Citation

Senat MV, Porcher R, Winer N, Vayssière C, Deruelle P, Capelle M, Bretelle F, Perrotin F, Laurent Y, Connan L, Langer B, Mantel A, Azimi S, Rozenberg P; Groupe de Recherche en Obstétrique et Gynécologie. Prevention of preterm delivery by 17 alpha-hydroxyprogesterone caproate in asymptomatic twin pregnancies with a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2013 Mar;208(3):194.e1-8. doi: 10.1016/j.ajog.2013.01.032. — View Citation

Serra V, Perales A, Meseguer J, Parrilla JJ, Lara C, Bellver J, Grifol R, Alcover I, Sala M, Martínez-Escoriza JC, Pellicer A. Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double-blind multicentre trial. BJOG. 2013 Jan;120(1):50-7. doi: 10.1111/j.1471-0528.2012.03448.x. Epub 2012 Aug 13. — View Citation

Skentou C, Souka AP, To MS, Liao AW, Nicolaides KH. Prediction of preterm delivery in twins by cervical assessment at 23 weeks. Ultrasound Obstet Gynecol. 2001 Jan;17(1):7-10. — View Citation

To MS, Fonseca EB, Molina FS, Cacho AM, Nicolaides KH. Maternal characteristics and cervical length in the prediction of spontaneous early preterm delivery in twins. Am J Obstet Gynecol. 2006 May;194(5):1360-5. Epub 2006 Apr 21. — View Citation

Vayssière C, Favre R, Audibert F, Chauvet MP, Gaucherand P, Tardif D, Grangé G, Novoa A, Descamps P, Perdu M, Andrini E, Janse-Marec J, Maillard F, Nisand I. Cervical length and funneling at 22 and 27 weeks to predict spontaneous birth before 32 weeks in twin pregnancies: a French prospective multicenter study. Am J Obstet Gynecol. 2002 Dec;187(6):1596-604. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm delivery	Rate of preterm delivery before 37.	up to 25 weeks from randomization