Does Progesterone Prevent Very Preterm Delivery in Twin Pregnancies?

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Preterm Delivery

Intervention / Treatment
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* Drug: Progesterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo pessaries containing peanut oil<br>|
| Active Comparator: Progesterone<br> | Drug: Progesterone<br>* Vaginal pessaries, 200 mg/day<br>* Other names: Utrogestan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of delivery < 34 weeks, in the study group versus the control group |  | Participants will be followed until 3 weeks after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical and neurological development of the children at 6 and 18 months |  | 2 years after delivery | 
| The relationship between cervical length and prophylactic progesterone treatment |  | Participants will be followed until 3 weeks after delivery | 
| Determination of proteomics and RNA in preterm delivery and term delivery and an evaluation of the effect of progesterone on proteomics and RNA |  | Participants will be followed until 3 weeks after delivery | 
| Assessment of the potential anti-inflammatory effect of progesterone by cytokine-measurements |  | Participants will be followed until 3 weeks after delivery | 
| Assessment of the effect of progesterone on CRH-levels in twin pregnancies |  | Participants will be followed until 3 weeks after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm delivery, Prevention, Twins, Progesterone