Premature Birth, Twin Pregnancy
Conditions
Keywords
Progesterone
Brief summary
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
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.
Interventions
DRUGProgesterone
Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week
Sponsors
Chiu Yee Liona Poon
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention 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'
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The median gestational age (in days) at delivery | At delivery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Within the first year | Intraventricular hemorrhage, respiratory distress syndrome, retinopathy of prematurity, or necrotizing entercolitis. |
| Need for neonatal special care | Between birth and 28 days of age | Admission to a neonatal intensive care unit, ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion |
Countries
Hong Kong
Outcome results
None listed