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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Premature Birth; Twin Pregnancy
• Intervention / Treatment: Drug: Progesterone

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 Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Prince Of Wales Hospital
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital
  • Hong Kong, Hong Kong
    • Kwong Wah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight		At delivery
The incidence of spontaneous preterm birth		Less than 34 weeks (237 days) of gestation
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

Collaborators and Investigators

• Sponsor: Chiu Yee Liona Poon
• Investigators: Principal Investigator: Liona CY Poon, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 7, 2018
• First Submitted That Met QC Criteria: May 27, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Progesterone
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 2016.594-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No