Pessary + Progesterone for Preventing Preterm Birth in Twins

(PROSPECT Trial)

Recruiting at 15 trial locations

Overseen By Rebecca Clifton, PhD

Age: Any Age

Sex: Female

Trial Phase: Phase 3

Sponsor: The George Washington University Biostatistics Center

Must not be taking: Glucocorticoids, Progesterone

Disqualifiers: Monoamniotic, Twin-twin transfusion, IUGR, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: up to 19 weeks

437 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol outlines a randomized trial of 630 women evaluating the use of micronized vaginal progesterone or pessary versus control (placebo) to prevent early preterm birth in women carrying twins and with a cervical length of less than 30 millimeters.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic oral glucocorticoid therapy or treated for hypertension with more than one agent, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

What data supports the idea that Pessary + Progesterone for Preventing Preterm Birth in Twins is an effective treatment?

The available research shows that using a combination of the Arabin cervical pessary and progesterone can be effective in reducing the risk of preterm birth. For example, in a study involving patients with placenta previa, those who received both the pessary and progesterone had a significantly lower rate of preterm labor before 34 weeks compared to those who only received progesterone. Additionally, this combination also reduced the rate of bleeding during pregnancy. However, there is no clear consensus on whether this method is superior to other treatments like cervical cerclage or progesterone alone, as different studies have shown varying results. ^{1 2 3 4 5}

What safety data exists for using pessary and progesterone to prevent preterm birth in twins?

The safety data for using the Arabin cervical pessary and vaginal progesterone to prevent preterm birth includes several studies. These studies have explored the combination of these treatments in high-risk pregnancies, including those with a short cervical length and placenta previa. The combination has been associated with reduced rates of preterm labor and bleeding during pregnancy. However, there is no clear consensus on the superiority of this method over others, and no specific guidelines for its use during pregnancy have been established. Overall, the combination appears to be safe and effective in reducing preterm birth risks, but further research is needed to establish definitive guidelines. ^{1 2 3 4 5}

Is the treatment Arabin Pessary and the drug Progesterone promising for preventing early birth in twins?

Yes, using the Arabin Pessary along with the drug Progesterone seems promising for preventing early birth. Studies show that this combination can reduce the chances of early delivery and complications during pregnancy compared to using Progesterone alone. ^{1 4 5 6 7}

Research Team

Monica Longo, MD

Principal Investigator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Joseph Biggio, MD

Principal Investigator

Maternal Fetal Medicine Units (MFMU) Network

Eligibility Criteria

This trial is for pregnant women with twin gestations, between 16 and 23 weeks along, who have a cervix shorter than 30 mm. It's not for those with placenta previa, serious maternal illnesses, planned cerclage or existing cerclage, monoamniotic twins, twin-twin transfusion syndrome, severe IUGR in either fetus, major fetal anomalies or imminent demise of a fetus.

Inclusion Criteria

Twin gestation with cardiac activity in both fetuses. Higher order multifetal gestations reduced to twins, either spontaneously or therapeutically, are not eligible unless the reduction occurred by 13 weeks 6 days project gestational age

Cervical length on transvaginal examination of less than 30 mm by a study certified sonographer

Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound

Exclusion Criteria

I do not have liver disease.

My cervix is dilated 3 cm or more, or my membranes have prolapsed.

Monoamniotic gestation, due to increased risk of adverse pregnancy outcome

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either micronized vaginal progesterone, pessary, or placebo from randomization to less than 35 weeks gestation

up to 19 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neonatal outcomes

up to 6 weeks

Treatment Details

Interventions

• Arabin Pessary
• Placebo
• Vaginal progesterone

Trial Overview The study tests if micronized vaginal progesterone or an Arabin pessary can prevent early preterm birth in women carrying twins with a short cervix compared to placebo. A total of 630 participants will be randomly assigned to one of these interventions.

Participant Groups

Group I: Progesterone Active Control 1 Intervention

200mg micronized vaginal progesterone softgel capsule, daily from randomization to \< 35 wks

Group II: Arabin Pessary Active Control 1 Intervention

placement management from randomization to \< 35 wks

Group III: Placebo Placebo Group 1 Intervention

placebo softgel capsule, daily from randomization to \< 35 wks

Arabin Pessary is already approved in European Union for the following indications:

Approved in European Union as Arabin Pessary for:

• Prevention of preterm birth in women with a short cervix
• Support for the cervix in pregnant women with threatening preterm labor

Who Is Running the Clinical Trial?

The George Washington University Biostatistics Center

Lead Sponsor

Trials

27

Recruited

111,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

The combination of the Arabin pessary with progesterone significantly reduces the rate of vaginal dysbiosis during pregnancy and postpartum, indicating a potential benefit in managing infections in high-risk pregnant women.

This combined treatment also shows a lower incidence of abnormal placental location migration compared to progesterone-only management, suggesting improved outcomes for placental health in high-risk pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of arabin pessary, cervical cerclage and medical management for preterm birth prevention in high-risk pregnancies. Barinov, SV., Shamina, IV., Lazareva, OV., et al.[2018]

The review highlights that while the Arabin Pessary is commonly used to prevent spontaneous preterm birth (SPTB), there is no clear evidence that it is superior to other methods like cervical cerclage or vaginal progesterone, based on a comprehensive literature review.

Despite its widespread clinical use, there are currently no established guidelines for the management and application of the Arabin Pessary during pregnancy, indicating a need for further research and standardization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the Arabin Pessary really useful in preventing preterm birth? A review of literature. Piccioni, MG., Del Negro, V., Bruno Vecchio, RC., et al.[2021]

The study involving 43 pregnant women at risk of preterm birth showed that using the Arabin cervical pessary along with intravaginal progesterone is a safe and feasible method for preventing preterm birth, with an average delivery at 35 weeks and 5 days.

Twin pregnancies had a significantly higher rate of preterm birth compared to singleton pregnancies, highlighting the need for further research to evaluate the efficacy of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[First year experience using arabin cervical pessary with intravaginal micronized progesterone for the prevention of preterm birth in patients with mid-trimester short cervix]. Zimerman, AL., Neeman, O., Wiener, Y., et al.[2016]

In a study of 286 pregnant women with a short cervical length, a combination treatment of vaginal progesterone, cervical cerclage, and Arabin cervical pessary (group A) showed a higher prevalence of risk factors like cervical incompetence, yet did not lead to a significantly lower rate of preterm delivery compared to other treatment groups.

The results suggest that this combined treatment approach may be effective in managing pregnancies at high risk for preterm birth, potentially prolonging gestation and improving outcomes, but further research is needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined therapy with vaginal progesterone, Arabin cervical pessary and cervical cerclage to prevent preterm delivery in high-risk women. Shor, S., Zimerman, A., Maymon, R., et al.[2022]

In a study of 217 patients with placenta previa, the combination of the Arabin cervical pessary and progesterone significantly reduced the rate of bleeding during pregnancy to 11.3%, compared to 33.1% in the control group that received progesterone only.

The combination treatment also led to a 2.7 times lower incidence of preterm labor before 34 weeks and improved placental migration rates, indicating enhanced safety and efficacy in managing placenta previa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cervical pessary and progesterone therapy in the phenomenon of placenta previa migration. Barinov, SV., Shamina, IV., Di Renzo, GC., et al.[2020]

This study aims to compare the effectiveness of vaginal progesterone alone versus a combination of vaginal progesterone and a cervical pessary in preventing preterm birth in women with a short cervix, involving 936 participants across 17 health facilities in Brazil.

The trial will assess neonatal adverse events as the primary outcome, providing insights into whether the combination treatment offers additional benefits over progesterone alone in reducing the risk of preterm birth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial on the use of pessary plus progesterone to prevent preterm birth in women with short cervical length (P5 trial). Pacagnella, RC., Mol, BW., Borovac-Pinheiro, A., et al.[2020]

In a study of 202 pregnant women with short cervical length, those treated with a combination of Arabin cervical pessary and vaginal progesterone had a significantly lower rate of preterm delivery before 34 weeks compared to those treated with vaginal progesterone alone (7.4% vs. 17.6%).

The combined treatment also resulted in a longer gestation period, with the study group delivering approximately one week later than the control group (37.2 weeks vs. 36.2 weeks), suggesting that this approach may be more effective in managing pregnancies at risk for preterm delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arabin cervical pessary with vaginal progesterone versus vaginal progesterone for preventing preterm delivery. Melcer, Y., Kovo, M., Maymon, R., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative assessment of arabin pessary, cervical cerclage and medical management for preterm birth prevention in high-risk pregnancies. [2018]

2. France pubmed.ncbi.nlm.nih.gov

Is the Arabin Pessary really useful in preventing preterm birth? A review of literature. [2021]

3. Israel pubmed.ncbi.nlm.nih.gov

[First year experience using arabin cervical pessary with intravaginal micronized progesterone for the prevention of preterm birth in patients with mid-trimester short cervix]. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Combined therapy with vaginal progesterone, Arabin cervical pessary and cervical cerclage to prevent preterm delivery in high-risk women. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The role of cervical pessary and progesterone therapy in the phenomenon of placenta previa migration. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A randomized controlled trial on the use of pessary plus progesterone to prevent preterm birth in women with short cervical length (P5 trial). [2020]

7. England pubmed.ncbi.nlm.nih.gov

Arabin cervical pessary with vaginal progesterone versus vaginal progesterone for preventing preterm delivery. [2021]