Official Title: “Effectiveness of Vaginally Administered Progesterone to Prevent Preterm Delivery in Twin Pregnancies - A Multicentre Randomized Trial”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Progesterone
  • Vaginal pessaries, 200 mg/day
• Drug: Placebo
  • Placebo pessaries containing peanut oil

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
  • 325 women
• Active Comparator: Progesterone
  • 325 women

Primary Measures

• The incidence of delivery < 34 weeks, in the study group versus the control group
  • Time Frame: Delivery
    Safety Issue?: No

Secondary Measures

• Physical and neurological development of the children at 6 and 18 months
  • Time Frame: 2 years after delivery
    Safety Issue?: Yes
• The relationship between cervical length and prophylactic progesterone treatment
  • Time Frame: Delivery
    Safety Issue?: No
• Determination of proteomics and RNA in preterm delivery and term delivery and an evaluation of the effect of progesterone on proteomics and RNA
  • Time Frame: Delivery
    Safety Issue?: No
• Assessment of the potential anti-inflammatory effect of progesterone by cytokine-measurements
  • Time Frame: Delivery
    Safety Issue?: No
• Assessment of the effect of progesterone on CRH-levels in twin pregnancies
  • Time Frame: Delivery
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rigshospitalet, Denmark

Overall Clinical Trial Officials and Contacts

Line Rode, MD Principal Investigator Ultrasound Clinic 4002, Rigshospitalet  

Overall Contact: Line Rode, MD 45-3545-3722 line.rode@rh.dk

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00329914

Study ID Number: predict2006

ClinicalTrials.gov Identifier: NCT00329914

Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Trial homepage