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

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ClinicalTrials.gov Identifier: NCT02518594
Recruitment Status : Recruiting
First Posted : August 10, 2015
Last Update Posted : March 7, 2024
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

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.

Condition or disease Intervention/treatment Phase
Short Cervical Length Drug: Vaginal progesterone Drug: Placebo Device: Arabin Pessary Phase 3

Detailed Description:

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.

Multiple gestation increases the risk of preterm delivery. Babies born preterm have increased rates of neonatal mortality and long-term neurodevelopmental morbidities. Short cervical length is known to be an important risk factor for spontaneous preterm birth and to occur more frequently in women with a twin gestation. Although there is no evidence that progesterone reduces the risk of preterm birth in multifetal gestation, there is evidence that progesterone reduces the risk of prematurity in singleton gestations complicated with a short cervix. The Arabin pessary has also been shown to reduce the risk of preterm birth among singletons with a short cervix, and in a secondary subgroup analysis of a recent study of the use of pessary in multiple gestations, women with a cervical length < 25th percentile had a significantly reduced risk of the primary composite neonatal adverse outcome. Secondary analysis of studies of vaginal progesterone in multiple gestation with a short cervix also suggest a possible beneficial effect on preterm delivery.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 630 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Women will be randomly assigned to study drug (200 mg micronized progesterone daily), placebo study drug appearing identical to progesterone capsule, or Arabin pessary.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Participants and care providers will be blinded to active study drug vs. placebo.
Primary Purpose: Prevention
Official Title: A Randomized Trial of Pessary and Progesterone for Preterm Prevention in Twin Gestation With a Short Cervix
Actual Study Start Date : November 13, 2015
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pregnancy

Arm Intervention/treatment
Active Comparator: Progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Drug: Vaginal progesterone
200mg micronized vaginal progesterone softgel capsule, daily from randomization to < 35 wks
Other Name: Prometrium

Placebo Comparator: Placebo
placebo softgel capsule, daily from randomization to < 35 wks
Drug: Placebo
placebo softgel capsule, daily from randomization to < 35 wks

Active Comparator: Arabin Pessary
placement management from randomization to < 35 wks
Device: Arabin Pessary
Placement management from randomization to < 35 wks




Primary Outcome Measures :
  1. Delivery or fetal loss of either twin prior to 35 weeks gestation [ Time Frame: prior to 35 weeks gestation ]
    Preterm delivery or fetal loss prior to 35 weeks gestation


Secondary Outcome Measures :
  1. Interval from randomization to delivery (or fetal demise) [ Time Frame: Randomization to delivery can be up to 26 weeks ]
    Randomization may begin at 16 weeks, and most patients will be delivered by 41 weeks

  2. Gestational age at delivery [ Time Frame: Randomization to delivery can be up to 26 weeks ]
    Gestational age at the time of delivery. Randomization begins at 16 weeks gestation

  3. Preterm delivery or fetal demise of either twin prior to 28 weeks gestation, 32 weeks gestation, and 37 weeks gestation [ Time Frame: From randomization to up to 37 weeks gestation (up to 21 weeks) ]
    Preterm delivery or fetal loss of either twin prior to 28 weeks gestation; prior to 32 weeks gestation; and prior to 37 weeks gestation

  4. Spontaneous preterm delivery (following preterm labor or pPROM) < 35 weeks gestation and < 32 weeks gestation [ Time Frame: From randomization to delivery (up to 19 weeks) ]
    Spontaneous preterm delivery before 35 weeks gestation and 32 weeks gestation

  5. Indicated preterm delivery < 35 weeks [ Time Frame: From randomization to delivery (up to 19 weeks) ]
    Preterm delivery prior to 35 weeks gestation with medical indications

  6. Cesarean delivery [ Time Frame: Randomization to delivery can be up to 26 weeks ]
    Delivery by cesarean

  7. Fetal or neonatal death [ Time Frame: Up to 28 days postnatal age ]
    Fetal or neonatal death

  8. Small for gestational age [ Time Frame: Randomization to delivery can be up to 26 weeks ]
    Less than 5th percentile weight for gestational age, by sex and race of the infant based on United States birth certificate data

  9. Composite neonatal outcome [ Time Frame: Birth to neonatal discharge or death, whichever is first (up to 6 weeks) ]
    Fetal or neonatal death, RDS, grade III or IV IVH, PVL, Stage 2 or 3 NEC, BPD, Stage III or higher ROP, or early onset sepsis

  10. Length of hospital stay, need for NICU or intermediate care admission and length of stay if admitted [ Time Frame: Birth to neonatal discharge or death, whichever is first (up to 6 weeks) ]
    Length of hospital stay in days, any Neonatal ICU or intermediate care admission, or length of hospital or intermediate care stay in days



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound.
  3. Cervical length on transvaginal examination of less than 30 mm by a study certified sonographer.

Exclusion Criteria:

  1. Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization. There is no lower threshold of cervical length measurement threshold on ultrasound that is an exclusion criterion.
  2. Monoamniotic gestation, due to increased risk of adverse pregnancy outcome
  3. Twin-twin transfusion syndrome, due to increased risk of adverse pregnancy outcome
  4. Evidence of severe IUGR (intrauterine growth restriction) (<5th percentile for gestational age) in either fetus
  5. 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.
  6. Placenta previa, because of risk of bleeding and high potential for indicated preterm birth
  7. Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement.
  8. Symptomatic, untreated vaginal or cervical infection, also because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized.
  9. Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to the potential for significant patient discomfort or increasing genital tract viral spread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized. History of herpes is not an exclusion.
  10. 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
  11. More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer
  12. 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
  13. Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia
  14. Major maternal medical illness associated with increased risk for adverse pregnancy outcome or indicated preterm birth (treated hypertension requiring more than one agent, pre-gestational treatment for diabetes prior to pregnancy, chronic renal insufficiency failure defined by creatinine >1.4 mg/dL, carcinoma of the breast, conditions treated with chronic oral glucocorticoid therapy. Specifically, patients with seizure disorders, HIV, and other medical conditions not specifically associated with an increased risk of indicated preterm birth are not excluded. Prior cervical cone/LOOP/LEEP is not an exclusion criterion.
  15. Planned cerclage or cerclage already in place since it would preclude placement of a pessary
  16. Planned indicated delivery prior to 35 weeks
  17. Planned or actual progesterone treatment of any type or form after 15 weeks 6 days during the current pregnancy
  18. Allergy to progesterone, silicone, or excipients in the study drug, including peanuts or peanut oil in the study drug or placebo
  19. Known, suspected or history of breast cancer because breast cancer is a contraindication to the active study medication.
  20. Known liver dysfunction or disease because liver disease is a contraindication to the active study medication.
  21. Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality
  22. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
  23. Prenatal care or delivery planned elsewhere unless the study visits can be made as scheduled and complete outcome information can be obtained

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02518594


Contacts
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Contact: Rebecca Clifton, PhD 301-881-9260 rclifton@bsc.gwu.edu

Locations
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United States, Alabama
University of Alabama - Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jeannette Boyce, RN    412-527-8118    tessje@upmc.edu   
Principal Investigator: Alan TN Tita, MD         
United States, California
The Regents of the University of California, San Francisco Recruiting
San Francisco, California, United States
Contact: Natalie Oman, MPH    206-718-4703    natalie.oman@ucsf.edu   
Principal Investigator: Mary Norton, MD         
United States, Colorado
University of Colorado Active, not recruiting
Denver, Colorado, United States, 80045
United States, Illinois
Northwestern University-Prentice Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Gail Mallett    312-503-3200    g-mallett@northwestern.edu   
Principal Investigator: Lynn Yee, MD, MPH         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Sabine Bousleiman    212-305-4348    sb1080@columbia.edu   
Principal Investigator: Uma Reddy, MD         
United States, North Carolina
University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Kelly Clark, RN    919-350-6117    kelly_clark@med.unc.edu   
Principal Investigator: John M Thorp, Jr., MD         
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Jennifer Ferrara, RNC MSN    919-681-6176    jennifer.ferrara@duke.edu   
Principal Investigator: Geeta K Swamy, MD         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44109
Contact: Abigail Pierse, BS    216-778-8443    apierse@metrohealth.org   
Principal Investigator: Kelly Gibson, MD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Anna Bartholomew, RN, BSN    614-685-3229    anna.bartholomew@osumc.edu   
Principal Investigator: Maged Costantine, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Christina Pizzi, RN    267-273-8574    christina.pizzi@pennmedicine.upenn.edu   
Principal Investigator: Samuel Parry, MD         
Magee Women's Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Jeanette Boyce, RN    412-527-8118    tessje@upmc.edu   
Principal Investigator: Hyagriv Simhan, MD, MS         
United States, Rhode Island
Brown University Recruiting
Providence, Rhode Island, United States, 02905
Contact: Angelica DeMartino, RN, BSN    401-274-1122 ext 48521    amdemartino@wihri.org   
Principal Investigator: Dwight Rouse, MD         
United States, Texas
University of Texas - Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Amelia Nounes, MSN, RN    409-747-1758    aanounes@utmb.edu   
Principal Investigator: Luis Pacheco, MD         
University of Texas - Houston Recruiting
Houston, Texas, United States, 77030
Contact: Felecia Ortiz, RN    713-500-6467    Felecia.Ortiz@uth.tmc.edu   
Principal Investigator: Hector Mendez-Figueroa, MD         
Baylor College of Medicine Recruiting
Houston, Texas, United States
Contact: Christine Reed, RN    832-826-7377    Christina.Reed@bcm.edu   
Contact: Jia Chen, RN    713-798-3798    Jia.Chen@bcm.edu   
Principal Investigator: Catherine Eppes, MD, MPH         
United States, Utah
University of Utah Medical Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Amber Sowles, RN BSN    801-585-5499    amber.sowles@hsc.utah.edu   
Principal Investigator: Torri Metz, MD         
Sponsors and Collaborators
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Study Chair: Joseph Biggio, MD Maternal Fetal Medicine Units (MFMU) Network
Study Director: Monica Longo, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT02518594    
Other Study ID Numbers: HD36801-PROSPECT
U24HD036801 ( U.S. NIH Grant/Contract )
UG1HD087230 ( U.S. NIH Grant/Contract )
UG1HD027869 ( U.S. NIH Grant/Contract )
UG1HD027915 ( U.S. NIH Grant/Contract )
UG1HD034208 ( U.S. NIH Grant/Contract )
UG1HD040500 ( U.S. NIH Grant/Contract )
UG1HD040485 ( U.S. NIH Grant/Contract )
UG1HD053097 ( U.S. NIH Grant/Contract )
UG1HD040544 ( U.S. NIH Grant/Contract )
UG1HD040545 ( U.S. NIH Grant/Contract )
UG1HD040560 ( U.S. NIH Grant/Contract )
UG1HD040512 ( U.S. NIH Grant/Contract )
UG1HD087192 ( U.S. NIH Grant/Contract )
UG1HD068282 ( U.S. NIH Grant/Contract )
UG1HD068258 ( U.S. NIH Grant/Contract )
UG1HD068268 ( U.S. NIH Grant/Contract )
First Posted: August 10, 2015    Key Record Dates
Last Update Posted: March 7, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses.
Keywords provided by The George Washington University Biostatistics Center:
women
cervical length of less than 30 millimeters
carrying twins
short cervix
Additional relevant MeSH terms:
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Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs