Clinical trial NCT00329914: Does Progesterone Prevent Very Preterm Delivery in Twin Pregnancies?
Official title: Effectiveness of Vaginally Administered Progesterone to Prevent Preterm Delivery in Twin Pregnancies - A Multicentre Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Preterm Delivery
Keywords: Preterm delivery
Prevention
Twins
Progesterone
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: The Danish Medical Research Council
name: The Danish Medical Society in Copenhagen
name: AP Moeller Foundation
First posted: 2006-05-25
Enrollment: 677
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to determine whether a daily dose of 200 mg progesterone administered vaginally from 20-23 to 34 weeks' gestation will reduce the rate of preterm delivery amongst twin pregnancies.

Detailed description: Multiple gestations account for 2% of all pregnancies, but cause more than 10% of the cases of preterm delivery. Due to increasing maternal age and use of assisted reproduction the number of multiple gestations is larger than ever. If markers of preterm delivery can be identified and means of preventing preterm delivery are found, it will be possible to reduce the number of children admitted to hospital because of prematurity.

Recently, two larger randomised studies investigated the effect of progesterone in singleton pregnancies of women who had previously delivered preterm. They both found a significant reduction in the preterm delivery rate in the progesterone group compared to a placebo group.

The study will be performed as a randomized, double-blind placebo controlled study of twin pregnancies in Denmark and Austria. The women will be randomised in a 1:1 ratio to two groups (progesterone versus placebo). Randomisation will be stratified per centre and according to chorionicity, as the risk of preterm delivery is doubled in monochorionic twins compared to dichorionic twins.

Eligibility criteria: Inclusion Criteria:

* Twin pregnancy
* Informed consent
* 18-23 weeks' gestation
* Participants must be fluent in the language spoken in the respective centres

Exclusion Criteria:

* Age \< 18 years
* Known allergy to progesterone or peanuts
* Active thromboembolic disorders or a history of hormone-associated thromboembolic disorders
* Rupture of membranes at the time of inclusion
* Monoamniotic twins
* Pregnancies treated for or with signs of twin-to-twin transfusion syndrome at inclusion
* Multiple pregnancies reduced to twin pregnancies
* Known significant structural or chromosomal fetal abnormality
* Chorionicity not assessed before 15 weeks
* Known or suspected malignancy in genitals or breasts
* Known liver disease

Primary outcomes:
measure: The incidence of delivery < 34 weeks, in the study group versus the control group
timeFrame: Participants will be followed until 3 weeks after delivery
Secondary outcomes:
measure: Physical and neurological development of the children at 6 and 18 months
timeFrame: 2 years after delivery
measure: The relationship between cervical length and prophylactic progesterone treatment
timeFrame: Participants will be followed until 3 weeks after delivery
measure: Determination of proteomics and RNA in preterm delivery and term delivery and an evaluation of the effect of progesterone on proteomics and RNA
timeFrame: Participants will be followed until 3 weeks after delivery
measure: Assessment of the potential anti-inflammatory effect of progesterone by cytokine-measurements
timeFrame: Participants will be followed until 3 weeks after delivery
measure: Assessment of the effect of progesterone on CRH-levels in twin pregnancies
timeFrame: Participants will be followed until 3 weeks after delivery
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Graz University Hospital
city: Innsbruck
country: Austria
facility: Innsbruck University Hospital
city: Klagenfurt
country: Austria
facility: Klagenfurt Hospital
city: Vienna
country: Austria
facility: Vienna University Hospital
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Aarhus
country: Denmark
facility: Skejby Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Glostrup
country: Denmark
facility: Glostrup Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hilleroed
country: Denmark
facility: Hilleroed Hospital
city: Holbaek
country: Denmark
facility: Holbaek Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Soenderborg
country: Denmark
facility: Soenderborg Hospital
city: Viborg
country: Denmark
facility: Viborg Hospital
Study officials:
affiliation: Ultrasound Clinic 4002, Rigshospitalet
name: Line Rode, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ultrasound Clinic 4002, Rigshospitalet
name: Ann Tabor, professor
role: STUDY_DIRECTOR
References:
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.
citation: Klein K, Rode L, Nicolaides KH, Krampl-Bettelheim E, Tabor A; PREDICT Group. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies: secondary analysis of a placebo-controlled randomized trial and meta-analysis. Ultrasound Obstet Gynecol. 2011 Sep;38(3):281-7. doi: 10.1002/uog.9092.
citation: Rode L, Klein K, Larsen H, Holmskov A, Andreasen KR, Uldbjerg N, Ramb J, Bodker B, Skibsted L, Sperling L, Hinterberger S, Krebs L, Zingenberg H, Weiss EC, Strobl I, Laursen L, Christensen JT, Skogstrand K, Hougaard DM, Krampl-Bettelheim E, Rosthoj S, Vogel I, Tabor A. Cytokines and the risk of preterm delivery in twin pregnancies. Obstet Gynecol. 2012 Jul;120(1):60-8. doi: 10.1097/AOG.0b013e31825bc3cd.