Clinical trial NCT03540225: Vaginal Progesterone for the Prevention of Preterm Birth in Twins
Official title: Vaginal Progesterone for the Prevention of Preterm Birth in Twins: A Pilot Randomised, Factorial Designed Trial (POPPET)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Premature Birth
Twin Pregnancy
Keywords: Progesterone
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2018-05-30
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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'
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The median gestational age (in days) at delivery
timeFrame: At delivery
Secondary outcomes:
measure: The incidence of spontaneous preterm birth
timeFrame: Less than 34 weeks (237 days) of gestation
measure: Birth weight
timeFrame: At delivery
measure: Stillbirth or neonatal death due to any cause
timeFrame: At delivery
measure: Major adverse outcomes before discharge from the hospital
timeFrame: Within the first year
measure: Need for neonatal special care
timeFrame: Between birth and 28 days of age
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Kwong Wah Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Liona CY Poon, MD
role: PRINCIPAL_INVESTIGATOR
References: