A Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix

NCT02518594 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 20 other identifiers: HD36801-PROSPECTU24HD036801UG1HD087230UG1HD027869UG1HD027915UG1HD034208UG1HD040500UG1HD040485UG1HD053097UG1HD040544UG1HD040545UG1HD040560UG1HD040512UG1HD087192UG1HD112063UG1HD112092UG1HD112096UG1HD068282UG1HD068258UG1HD068268
• Study Type: interventional
• Target: 1,311
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Short Cervical Length

Keywords

women; cervical length of less than 30 millimeters; carrying twins; short cervix

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Delivery or Fetal Loss of Either Twin Prior to 35 Weeks Gestation

  Number of Participants who had preterm delivery or fetal loss of either twin prior to 35 weeks gestation

  From randomization to 35 weeks gestation (a period of up to 19 weeks)

Secondary Outcomes (15)

• Days From Randomization to Delivery (or Fetal Demise)

  Randomization to delivery (a period of up to 26 weeks)

• Gestational Age at Delivery or Fetal Death

  Randomization to delivery (a period of up to 26 weeks)

• Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 28 Weeks Gestation

  From randomization to up to 28 weeks gestation (a period if up to 12 weeks)

• Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 32 Weeks Gestation

  From randomization to 32 weeks gestation (a period of up to 16 weeks)

• Number of Participants With Preterm Delivery or Fetal Demise of Either Twin Prior to 37 Weeks Gestation

  randomization to 37 weeks gestation (a period of up to 21 weeks)

Study Arms (3)

Progesterone

ACTIVE COMPARATOR

vaginal progesterone capsule

Drug: Vaginal progesterone

Placebo

PLACEBO COMPARATOR

placebo capsule

Drug: Placebo

Arabin Pessary

ACTIVE COMPARATOR

Arabin Pessary

Device: Arabin Pessary

Interventions

Vaginal progesterone DRUG

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

Also known as: Prometrium

Progesterone

Placebo DRUG

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

Placebo

Arabin Pessary DEVICE

placement and management of an Arabin Pessary from randomization to \< 35 wks

Arabin Pessary

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
• Cervical length on transvaginal examination of less than 30 mm by a study certified sonographer.

You may not qualify if:

• Monoamniotic gestation, due to increased risk of adverse pregnancy outcome
• Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome
• Evidence of severe IUGR (intrauterine growth restriction) (\<5th percentile for gestational age) in either fetus
• Fetal anomaly in either twin or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities). An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project EDC (estimated date of conception) must be performed prior to randomization to evaluate the fetuses for anomalies.
• Placenta previa, because of risk of bleeding and high potential for indicated preterm birth
• Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
• Symptomatic, untreated vaginal or cervical infection, also because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized.
• Rupture of membranes due to likelihood of pregnancy loss and preterm delivery as well as the risk of ascending infection which could be increased with pessary placement
• More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer
• Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery which is unlikely to be affected by progesterone
• Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia
• Planned cerclage or cerclage already in place since it would preclude placement of a pessary
• Planned indicated delivery prior to 35 weeks
• Planned or actual progesterone treatment of any type or form after 15 weeks 6 days during the current pregnancy
• Allergy to progesterone, silicone, or excipients in the study drug, including peanuts or peanut oil in the study drug or placebo

Sponsors & Collaborators

• The George Washington University Biostatistics Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (16)

University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

The Regents of the University of California, San Francisco

San Francisco, California, United States

Location

University of Colorado

Denver, Colorado, 80045, United States

Location

Northwestern University-Prentice Hospital

Chicago, Illinois, 60611, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Magee Women's Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02905, United States

Location

University of Texas - Galveston

Galveston, Texas, 77555, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Joseph Biggio, MD, MS
• Organization: Ochsner Health

joseph.biggio@ochsner.org

504 842 5574

Study Officials

• Joseph Biggio, MD

  Maternal Fetal Medicine Units (MFMU) Network

  STUDY CHAIR

• Monica Longo, MD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and care providers will be blinded to active study drug vs. placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Women will be randomly assigned to study drug (200 mg micronized progesterone daily), placebo study drug appearing identical to progesterone capsule, or Arabin pessary.

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: August 10, 2015
• Study Start: November 13, 2015
• Primary Completion: December 15, 2024
• Study Completion: February 18, 2025
• Last Updated: March 10, 2026
• Results First Posted: March 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (16)