POPPET: Vaginal Progesterone for the Prevention of Preterm Birth in Twins

Sponsor

Chiu Yee Liona Poon (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03540225

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Premature Birth Twin Pregnancy	Drug: Progesterone	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

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'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 (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Early Low-dose Arm Start from 11-14 week: 200 mg self-administered vaginal progesterone daily	Drug: Progesterone Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week Other Names: Utrogestan
Experimental: Early High-dose Arm Start from 11-14 week: 400 mg self-administered vaginal progesterone daily	Drug: Progesterone Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week Other Names: Utrogestan
Experimental: Late Low-dose Arm Start from 20-24 week: 200 mg self-administered vaginal progesterone daily	Drug: Progesterone Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week Other Names: Utrogestan
Experimental: Late High-dose Arm Start from 20-24 week: 400 mg self-administered vaginal progesterone daily	Drug: Progesterone Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week Other Names: Utrogestan

Outcome Measures

Primary Outcome Measures

The median gestational age (in days) at delivery [At delivery]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.

Contacts and Locations

Locations

	Site	City	Country
1	Kwong Wah Hospital	Hong Kong	Hong Kong
2	Prince of Wales Hospital	Hong Kong	Hong Kong
3	Princess Margaret Hospital	Hong Kong	Hong Kong
4	Queen Elizabeth Hospital	Hong Kong	Hong Kong

Sponsors and Collaborators

Chiu Yee Liona Poon

Investigators

Principal Investigator: Liona CY Poon, MD, Chinese University of Hong Kong

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Chiu Yee Liona Poon, Associate Professor (Clinical), Chinese University of Hong Kong

ClinicalTrials.gov Identifier:

NCT03540225

Other Study ID Numbers:

2016.594-T

First Posted:

May 30, 2018

Last Update Posted:

Jan 28, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Chiu Yee Liona Poon, Associate Professor (Clinical), Chinese University of Hong Kong

Progesterone

Additional relevant MeSH terms:

Premature Birth

Progesterone

Study Results

No Results Posted as of Jan 28, 2021