Vaginal Progesterone for the Prevention of Preterm Birth in Twins (POPPET)

Chiu Yee Liona Poon

Status and phase: Withdrawn; Phase 3

Conditions: Twin Pregnancy; Premature Birth

Treatments: Drug: Progesterone

Study type: Interventional

Funder types: Other

Identifiers

NCT03540225

2016.594-T

Details and patient eligibility

About

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.

Full 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.

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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0 participants in 4 patient groups

Early Low-dose Arm

Experimental group

Description:

Start from 11-14 week: 200 mg self-administered vaginal progesterone daily

Treatment:

Drug: Progesterone

Early High-dose Arm

Experimental group

Description:

Start from 11-14 week: 400 mg self-administered vaginal progesterone daily

Treatment:

Drug: Progesterone

Late Low-dose Arm

Experimental group

Description:

Start from 20-24 week: 200 mg self-administered vaginal progesterone daily

Treatment:

Drug: Progesterone

Late High-dose Arm

Experimental group

Description:

Start from 20-24 week: 400 mg self-administered vaginal progesterone daily

Treatment:

Drug: Progesterone