Vaginal Progesterone for the Prevention of Preterm Birth in Twins

Study Overview
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Brief Summary
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This trial is a randomised, multi-centre, 2 x 2 factorial designed pilot trial with two factors of 200mg vs. 400mg progesterone self-administered daily from 11-14 weeks' gestation vs. 20-24 weeks' gestation, to compare the median gestational age (in days) at delivery between the comparison groups.

Detailed Description
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Randomised studies in singleton pregnancies suggest that the risk of preterm birth can be decreased by using of progesterone. However, in twin pregnancies, no significant reduction in preterm birth has been demonstrated in any trial. One explanation for the lack of benefit of progesterone in previous twin studies may result from a suboptimal dosage. The investigators therefore hypothesize that progesterone dosages that are sufficient for singleton pregnancies are insufficient for twins and this is likely to be one of the reasons why prophylactic progesterone has failed to reduce preterm birth in twins. Another possible explanation for the negative findings in previous twin studies may result from administration beginning too late in the second-trimester. It is thought that the mechanism of preterm birth in twin pregnancies is more strongly related to exaggerated uterine distension, which may override any benefit of progesterone on the cervix after a threshold has been reached. It is also plausible that cervical shortening occurs earlier in twin pregnancies than with singletons, and that treatment is required before a threshold of shortening is reached or before any inflammation-mediated component to the initiation of preterm birth has been established as the biological mechanisms by which preterm birth occurs differ from those in singleton pregnancies.

Official Title
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Vaginal Progesterone for the Prevention of Preterm Birth in Twins: A Pilot Randomised, Factorial Designed Trial (POPPET)

Conditions
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Premature Birth, Twin Pregnancy

Intervention / Treatment
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* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Dichorionic diamniotic (DCDA) pregnancies Live fetuses at 11-13 weeks of gestation, Informed and written consent Exclusion Criteria: High-risk for aneuploidies, Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks or 20-24 weeks assessment, Hypersensitivity to progesterone, Women taking progesterone regularly or at any time within the previous 7 days, Concurrent participation in another drug trial or at any time within the previous 28 days, Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness, Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: 2 x 2 factorial designed trial with two factors of 200mg vs. 400mg vaginal progesterone daily from 11-14 weeks' gestation vs. 20-24 weeks'
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Low-dose Arm<br>Start from 11-14 week: 200 mg self-administered vaginal progesterone daily | Drug: Progesterone<br>* Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week<br>* Other names: Utrogestan;|
| Experimental: Early High-dose Arm<br>Start from 11-14 week: 400 mg self-administered vaginal progesterone daily | Drug: Progesterone<br>* Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week<br>* Other names: Utrogestan;|
| Experimental: Late Low-dose Arm<br>Start from 20-24 week: 200 mg self-administered vaginal progesterone daily | Drug: Progesterone<br>* Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week<br>* Other names: Utrogestan;|
| Experimental: Late High-dose Arm<br>Start from 20-24 week: 400 mg self-administered vaginal progesterone daily | Drug: Progesterone<br>* Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week<br>* Other names: Utrogestan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The median gestational age (in days) at delivery |  | At delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of spontaneous preterm birth |  | Less than 34 weeks (237 days) of gestation | 
| Birth weight |  | At delivery | 
| Stillbirth or neonatal death due to any cause |  | At delivery | 
| Major adverse outcomes before discharge from the hospital | Intraventricular hemorrhage, respiratory distress syndrome, retinopathy of prematurity, or necrotizing entercolitis. | Within the first year | 
| Need for neonatal special care | Admission to a neonatal intensive care unit, ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion | Between birth and 28 days of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progesterone