Pessary + Progesterone for Preventing Preterm Birth in Twins

(PROSPECT Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if either vaginal progesterone or an Arabin pessary (a device placed in the vagina to support the cervix) can prevent early preterm birth in women pregnant with twins. Researchers compare these treatments to a placebo to identify which is more effective in reducing early labor. Women pregnant with twins, who have a cervix shorter than 30 millimeters and no major pregnancy complications, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Arabin pessary is generally safe, but some risks exist. In one study, 6.2% of pregnancies using the pessary resulted in fetal death, compared to 3.4% in those not using it. Another study found that 32.2% of people using the pessary experienced more problems compared to another method.

For vaginal progesterone, studies have produced mixed results. One study found it did not significantly reduce the risk of early birth before 33 weeks in twin pregnancies. However, in other situations, it has been linked to a decrease in early births and related health issues.

Both treatments have been tested in many studies, indicating they are reasonably safe. However, each carries some risks that participants should consider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new approaches to preventing preterm birth in twins, a challenge with limited effective options. Unlike traditional treatments, which primarily focus on general hormonal support, the Arabin Pessary provides mechanical support to the cervix, potentially reducing the risk of early labor. Meanwhile, the use of vaginal progesterone offers a targeted hormonal approach, which may help stabilize pregnancy and prevent preterm labor by maintaining uterine quiescence. This combination of mechanical and hormonal strategies could offer a more comprehensive prevention method than current treatments alone.

What evidence suggests that this trial's treatments could be effective for preventing preterm birth in twins?

This trial will compare the effectiveness of the Arabin pessary and vaginal progesterone in preventing preterm birth in twin pregnancies. Research has shown that the Arabin pessary does not significantly reduce early births or negative outcomes in women with twin pregnancies and a short cervix. Studies have found similar results for vaginal progesterone, as it does not prevent early birth or improve outcomes in all twin pregnancies. However, one study noted that vaginal progesterone was linked to a 44% decrease in serious health issues and deaths in newborns. Overall, evidence suggests that both treatments have limited effectiveness in preventing early birth in twins, but vaginal progesterone may help reduce serious health problems in newborns. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Monoamniotic gestation, due to increased risk of adverse pregnancy outcome

Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for gestational age) in either fetus

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8287379/

The Arabin pessary to prevent preterm birth in women with ... In this study, the Arabin pessary did not reduce preterm birth or adverse neonatal outcomes in women with a twin pregnancy and a short cervix.

2. ajog.org ajog.org/article/S0002-9378(23)02059-8/fulltext

The Arabin cervical pessary for the prevention of preterm ... Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups.

3. obgproject.com obgproject.com/2022/02/18/pessary-for-preterm-birth-prevention-in-twin-pregnancies-with-short-cervix/

RCT Results: Does Pessary Prevent Preterm Birth in Twin ... The use of pessary in twin pregnancies with short cervix was not associated with any significant reduction in preterm birth, or other adverse ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1028455925001755

Cervical pessary for preterm-birth prevention among ... Among them, 155 cases gave birth at or after 34 weeks, with a rate of 88.1 % (CI 95 %: 82.3–92.5). The primary purpose of Arabin pessary was to maximize the ...

5. journals.plos.org journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004526

Cervical cerclage versus cervical pessary with or without ... In this prematurely halted study on pregnant women with twins and a CL ≤28 mm, cerclage and cervical pessary were comparably effective on PTB <34 weeks ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11844863/

Cervical cerclage versus cervical pessary with or without ... However, the use of cerclage was associated with significantly lower rates of preterm birth <28 weeks and perinatal death. The addition of 400 ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2807569

Cervical Pessary for Prevention of Preterm Birth in ... More specifically, fetal death occurred in 17 (6.2%) of 275 pregnancies in the pessary group and in 9 (3.4%) of 263 in the usual care group ( ...

8. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00524-8/fulltext

Pessary or cerclage (PC study) to prevent recurrent ... The composite of adverse perinatal outcomes occurred in 42 cases after pessary compared to 29 cases in cerclage (32.2% vs 23.2%; RR 1.4 95% CI ...

9. mdpi.com mdpi.com/2075-4418/15/12/1466

Pessary for Prevention of Preterm Birth and Perinatal ... The cervical pessary, a vaginal silicone device, supports the cervix and alters its angle, potentially reducing the risk of preterm birth [19]. Multiple ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8108362/

Use of the Arabin pessary in women at high risk for preterm ... The most frequent indications for Arabin pessary insertion were previous mid-trimester miscarriage (46.4%) and early preterm birth (17.2%). A ...