Clinical trial NCT02329535: Comparing Double Dose of Vaginal Progesterone to no Treatment for Prevention of Preterm Birth in Twins and Short Cervix
Official title: Comparing a Double Dose of Vaginal Progesterone to no Treatment for the Prevention of Preterm Birth in Twins Pregnancy and Short Cervix
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Premature Birth
Lead sponsor: HaEmek Medical Center, Israel
Sponsor class: OTHER
First posted: 2014-12-31
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Preterm delivery
timeFrame: up to 25 weeks from randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Haemek Medical Center
city: Nazareth
country: Israel
facility: The Nazareth hospital
Study officials:
affiliation: Head of delivery room, Department of OB-GYN, Emek medical center, Afula, Israel
name: Raed Salim, MD
role: STUDY_CHAIR
References:
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citation: Serra V, Perales A, Meseguer J, Parrilla JJ, Lara C, Bellver J, Grifol R, Alcover I, Sala M, Martinez-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.
citation: Senat MV, Porcher R, Winer N, Vayssiere 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 Obstetrique et Gynecologie. 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.
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. doi: 10.1016/j.ajog.2005.11.001. Epub 2006 Apr 21.
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.