Premature BirthPhase 3POPPETNCT03540225
Vaginal Progesterone for the Prevention of Preterm Birth in Twins
A Phase 3 study testing Progesterone in people with Premature Birth and Twin Pregnancy, run by Chiu Yee Liona Poon at 4 sites in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Birth, Twin Pregnancy
- What is being tested?
- Progesterone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 4 sitesHong Kong
- Study dates
- Apr 2020to Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Dichorionic diamniotic (DCDA) pregnancies
- Live fetuses at 11-13 weeks of gestation,
- Informed and written consent
Who cannot join
- 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 locations and contacts
4 sites in 1 country.
Hong Kong4 sites
Kwong Wah Hospital
Hong Kong
Prince of Wales Hospital
Hong Kong
Princess Margaret Hospital
Hong Kong
Queen Elizabeth Hospital
Hong Kong
About this study
Official title: 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.
Read the 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.
- Conditions
- Premature Birth, Twin Pregnancy
- Being tested
- Progesterone
- Keywords
- Progesterone
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called Utrogestan
Utrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week
| Study group | Role | What they receive |
|---|---|---|
| Early Low-dose Arm | Experimental | Start from 11-14 week: 200 mg self-administered vaginal progesterone daily Receives: Drug: Progesterone |
| Early High-dose Arm | Experimental | Start from 11-14 week: 400 mg self-administered vaginal progesterone daily Receives: Drug: Progesterone |
| Late Low-dose Arm | Experimental | Start from 20-24 week: 200 mg self-administered vaginal progesterone daily Receives: Drug: Progesterone |
| Late High-dose Arm | Experimental | Start from 20-24 week: 400 mg self-administered vaginal progesterone daily Receives: Drug: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The median gestational age (in days) at delivery
Measured: At delivery
Secondary outcomes (5)
The incidence of spontaneous preterm birth
Measured: Less than 34 weeks (237 days) of gestation
Birth weight
Measured: At delivery
Stillbirth or neonatal death due to any cause
Measured: At delivery
Major adverse outcomes before discharge from the hospital
Intraventricular hemorrhage, respiratory distress syndrome, retinopathy of prematurity, or necrotizing entercolitis.
Measured: 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
Measured: Between birth and 28 days of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study startApr 2020 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: Fail to sort out the logistics of study drugs due to funding problems
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- 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'
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiu Yee Liona Poon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Chiu Yee Liona Poon, Chinese University of Hong Kong
- Investigators
- Liona CY Poon, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03540225
- Sponsor's protocol ID
- 2016.594-T
- Acronym
- POPPET
- Status last verified
- Jan 2021
- First submitted
- 7 May 2018
- Last updated
- 28 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaginal Progesterone for the Prevention of Preterm Birth in Twins: A Pilot Randomised, Factorial Designed Trial (POPPET)
- ClinicalTrials.gov ID
- NCT03540225
- Acronym / sponsor ID
- POPPET / 2016.594-T
- Conditions
- Premature Birth, Twin Pregnancy
- Keywords
- Progesterone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Fail to sort out the logistics of study drugs due to funding problems
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Chiu Yee Liona PoonUniversity, hospital or other
- Study start
- Apr 2020 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 30 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- 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'
| Arm | Type | Receives |
|---|---|---|
| Early Low-dose Arm | Experimental | Drug: ProgesteroneStart from 11-14 week: 200 mg self-administered vaginal progesterone daily |
| Early High-dose Arm | Experimental | Drug: ProgesteroneStart from 11-14 week: 400 mg self-administered vaginal progesterone daily |
| Late Low-dose Arm | Experimental | Drug: ProgesteroneStart from 20-24 week: 200 mg self-administered vaginal progesterone daily |
| Late High-dose Arm | Experimental | Drug: ProgesteroneStart from 20-24 week: 400 mg self-administered vaginal progesterone daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 18 years
- Dichorionic diamniotic (DCDA) pregnancies
- Live fetuses at 11-13 weeks of gestation,
- Informed and written consent
Key exclusion criteria (7 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProgesteroneAlso: UtrogestanUtrogestan Vaginal 200 mg or 400 mg daily from 11-14 Week or 20-24 Week until 34 Week | Drug | Early High-dose Arm, Early Low-dose Arm, Late High-dose Arm, Late Low-dose Arm |
Primary outcome
The median gestational age (in days) at delivery
Time frame: At delivery
5 secondary outcomes
The incidence of spontaneous preterm birth
Time frame: Less than 34 weeks (237 days) of gestation
Birth weight
Time frame: At delivery
Stillbirth or neonatal death due to any cause
Time frame: At delivery
Major adverse outcomes before discharge from the hospital
Time frame: Within the first year
Need for neonatal special care
Time frame: Between birth and 28 days of age
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liona CY Poon, MD principal investigator
Chinese University of Hong Kong
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Progesterone in people with Premature Birth and Twin Pregnancy, run by Chiu Yee Liona Poon at 4 sites in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The median gestational age (in days) at delivery (time frame: At delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2021.